MIRM - NASDAQ

Hello, everyone, and welcome to the Mirum Pharmaceuticals Report Second Quarter 2025 Financial Results and provide Business Update. My name is Carla, and I will be coordinating your call today. [Operator Instructions]. I would now like to hand you over to your host, Andrew McKibben, SVP of Strategic Finance and Investor Relations, to begin. Please go ahead when you're ready.

Thanks, Carla, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals Second Quarter 2025 Conference Call. I'm joined today by our CEO, Chris Peetz; our President and Chief Operating Officer, Peter Radovich; our Chief Medical Officer, Joanne M. Quan; and Eric Bjerkholt, our Chief Financial Officer. Earlier today, Mirum issued a news release announcing the company's results for the second quarter of 2025. Copies of this news release and SEC filings can be found in the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we'll be making certain forward-looking statements based on management's current expectations, including statements regarding Mirum's programs and market opportunities for its approved medicines and product candidates. These statements represent our judgment and knowledge of events as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-Q and subsequent SEC filings for more information. With that said, I'd like to turn the call over to Chris. Chris?

Thanks, Andrew, and good afternoon, everyone. 2025 is shaping up to be another outstanding year for Mirum, a second quarter that underscores the momentum behind both our commercial medicines and our pipeline. Mirum was founded in 2018 with a vision of bringing life-changing medicines to patients with rare disease around the world. Today, we have 3 approved medicines with reimbursed patients in over 30 countries and a pipeline that is rapidly advancing opportunities in still larger settings, highlighted by 3 potentially pivotal studies reading out over the next 24 months. Our strategy is rooted in commercial execution, scientific innovation and financial discipline, and we're proud of the continued progress on all 3 fronts that we will cover today. On that note, on second quarter results, we are excited to share another strong update for Mirum with total revenues reaching $128 million or 64% growth over the second quarter last year. Livmarli is a key driver of these results and is continuing to bring substantial benefit to patients and to build a differentiated position with physicians. As the top line suggests, we are reaching more patients than we initially anticipated. Given the growth we are seeing across our medicines, we are raising our full year guidance for 2025 to be $490 million to $510 million, positioning us for another year of close to 50% top line growth. Turning to the pipeline, the progress we are making is setting the stage for an exciting 2026, where we have a clear path to 3 late-stage milestones. In particular, the VISTAS Phase IIb study in primary sclerosing cholangitis or PSC, is on track to complete enrollment this quarter with top line data expected in the second quarter next year. Now this program passed its interim analysis last year and the consistent precedent data for IBAT inhibition across other cholestatic settings gives us confidence in the potential of volixibat in PSC. Exciting steps lie ahead to potentially bring this much-needed treatment to PSC patients. We are also seeing excellent momentum in our VANTAGE PBC and EXPAND studies and are looking forward to starting our Phase II study of MRM-3379 in Fragile X syndrome now that we have FDA feedback on the program, which Joanne will tell you more about shortly. I would also like to say thank you to the Mirum team, whose dedication to bringing high-impact medicines to patients has made all this progress possible. I'm proud of how this group has come together to create a high-growth, cash flow positive rare disease leader with an exciting pipeline. And with that, I'll hand the call over to Peter to walk through the commercial performance in more detail. Peter?

Thanks, Chris. Q2 was another strong quarter for Mirum with total net product sales of approximately $128 million, driven by continued momentum across Livmarli in both the United States and international markets as well as solid performance from our bile acid portfolio. In the U.S., Livmarli demand remains strong with -- in Alagille syndrome and PFIC with approximately $57 million in net product sales for the quarter. Notably, we are seeing more PFIC patients than we had originally anticipated, which we believe is due in part to increased disease awareness and broader use of genetic testing, leading to more PFIC diagnoses in patients with later onset cholestasis. While PFIC is often associated with clinical presentation in infants, we're increasingly seeing PFIC patients presenting later in childhood, adolescents or even adulthood. An expanding recognition of this variability and highlighting the importance of genetic testing across age groups has been a core focus of our launch strategy. We're also seeing real synergy between the approved Alagille syndrome and PFIC indications with providers increasingly viewing Livmarli as a preferred treatment across these settings of pediatric cholestasis. The combination of these factors is translating into a meaningful uptick in volume growth. Importantly, our recent U.S. launch of the single tablet per dose formulation in June adds meaningful convenience for patients, though I'll note that Q2 results reflect the performance of our oral solution. Internationally, we are seeing durable Livmarli growth across both direct and partner markets with $31 million in net product sales. This was driven by expanding reimbursement and growing demand as well as strong performance in our partner markets. In Q2, our partner, Takeda, secured reimbursement in Japan and launched Livmarli in June with promising demand observed in the initial days of commercialization. Under our license agreement with Takeda, we received large periodic orders for Livmarli, creating quarter- to-quarter variation in international product sales. We also saw strong performance from our bile acid portfolio with CTEXLI and COBACHOLBAM contributing approximately $40 million in revenue. These medicines continue to benefit from steady demand and increased engagement following the CTEXLI approval earlier this year. Given the momentum across our medicines, we are raising full year revenue guidance to $490 million to $510 million, driven largely by Livmarli's strong performance, particularly growth in our international business, steady increase in Alagille demand and our PFIC launch in the U.S. It's an exciting time for realizing Livmarli's potential. Looking long term, with the current trends in Alagille syndrome and PFIC and the label expansion opportunity in ultra-rare cholestasis, we aim to unlock through the EXPAND study. We believe Livmarli ultimately has the potential to be a $1 billion-plus revenue brand. We're excited about continuing to execute to realize that potential and prepare for potential launches ahead of our clinical pipeline. And for an update on the pipeline, I'll turn it over to Joanne.

Thanks, Peter. I'm pleased to share updates on the continued progress of our clinical pipeline, where we're seeing strong interest and engagement across all studies. Starting with volixibat, we're very encouraged by the momentum in our VISTAS study for patients with pruritus due to PSC. The last patients are in screening now, keeping us on track to complete enrollment this quarter and on track for expected top line data in the second quarter of 2026. With regards to PBC, the VANTAGE study is proceeding nicely, and we expect to complete enrollment next year. The EXPAND study evaluating Livmarli in additional settings of cholestatic pruritus is also progressing well, and we expect to complete enrollment in 2026. Finally, I'm excited to share more on MRM-3379, our brain-penetrant PDE4D inhibitor for Fragile X syndrome. We had the opportunity to discuss the program and endpoints with the FDA in a pre-IND meeting earlier this year, and our IND has recently cleared. We are on track to initiate the Phase II study by the end of the year. Our study will enroll approximately 52 male participants aged 16 to 45 with Fragile X syndrome. We will enroll males who are confirmed genetically, what is called full mutation, as these patients are known to be most severely affected from a cognitive standpoint and therefore, have the greatest unmet need for new therapy. This is a randomized, double-blind, placebo-controlled study evaluating 3 active doses in order to identify the optimal dose. An additional open-label cohort will include approximately 8 younger patients, males aged 13 to less than 16 at the lowest dose to evaluate PK and allow us to move into younger populations in subsequent trials. The primary endpoint is safety and tolerability and the key secondary efficacy endpoint is a change from baseline at week 12 on the NIH toolbox crystallized cognition composite, a well-recognized cognitive measure also used by other programs in the space. Based on FDA feedback, we do anticipate that this ultimately will be the primary endpoint in Phase III. We're excited by the pace and engagement across our pipeline and look forward to sharing further updates in the coming quarters. I will now hand the call over to Eric to discuss our financial results for the quarter. Eric?

Thanks, Joanne, and good afternoon, everyone. We delivered another solid quarter of financial performance, highlighted by total net product revenue of $128 million, representing a 64% increase over the prior year and reflecting growth across all our commercial medicines. Total operating expense for the quarter ended June 30 was $133 million, which includes R&D expense of $46 million, SG&A expense of $63 million and cost of sales of $23 million. Expenses for the quarter included noncash stock-based compensation expense of $18 million and intangible amortization and other noncash items of $6 million. The intangible amortization and other noncash items expense are largely reflected in our cost of sales. We were operating cash flow positive for the quarter and expect to continue to be cash flow positive for the full year. Our cash operating margins continue to improve. For example, our cash contribution margin from our Commercial business exceeded 50% in the second quarter. Cash, cash equivalents and investments were $322 million at June 30, a $29 million increase from the end of last year. We continue to be well funded and financially independent, providing us the resources required to expand our patient impact and grow our business. With that, I'll turn the call back to Chris.

Thanks, Eric. I want to take a moment again to acknowledge the incredible efforts of the Mirum team. The progress we've made so far this year, both commercially and across the pipeline reflects our continued commitment to delivering life-changing medicines for patients with rare disease. We are operating from a position of strength and the opportunities ahead make this an exciting time for Mirum. We have a clear strategy, the right team in place and a growing impact on the lives of patients and families around the world. And with that, operator, please open the call for questions.

[Operator Instructions]. And our first question comes from Gavin Clark-Gartner with Evercore.

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.

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.

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.

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 ].

The next question comes from Jessica Fye with JPMorgan.

This is [ Bill ] on for Jess. 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?

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.

The next question comes from Ryan Deschner with Raymond James.

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?

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.

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.

So the next question comes from Brian Skorney with Baird.

This is Luke on for Brian. 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?

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.

Yes. And specifically, in Q2 It was -- $11 million was the number of the Q2 number.

The next question comes from Mike Ulz with Morgan Stanley.

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?

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.

The next question comes from Mani Foroohar with Leerink Partners.

You have Ryan on for Mani. 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?

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.

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.

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.

The next question comes from Josh Schimmer with Cantor Fitzgerald.

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?

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.

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.

The next question comes from David Lebowitz with Citi.

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?

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.

[Operator Instructions]. The next question comes from Jonathan Wolleben with Citizens.

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?

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.

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?

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.

So the next question comes from Swayampakula Ramakanth with H.C. Wainwright.

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?

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.

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.

And that was the final question. And that does conclude the Q&A portion of today's call. So I will hand back over to Chris Peetz for any final comments.

Great. Thanks again for joining us today and for your continued support. We look forward to updating you in the quarters ahead. Have a great afternoon.