Mirum Pharmaceuticals Inc (MIRM) 2025 Q2 法說會逐字稿

Hello, everyone, and welcome to the Mirum Pharmaceuticals reports second-quarter 2025 financial results and [provided] 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 of 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 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 the 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're under no duty to update the 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, the 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 for patients with rare disease around the world. Today, we have three approved medicines with reimbursed patients in over 30 countries, the pipeline that is rapidly advancing opportunities and still larger settings highlighted by three 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 three fronts that we will cover today.

On that note, on second-quarter results, we're excited to share another strong update from Mirum, with total revenues is reaching $128 million or 64% growth over the second quarter last year. LIVMARLI is the key driver of these results and it's 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 three late-stage milestones. In particular, the VISTAS Phase 2b 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. As this program passed its interim analysis last year, the consistent precedent data for IBAT inhibition across other cholestatic settings gives us confidence in the potential of the (inaudible) of that NTSE. Exciting steps lie ahead, potentially bringing this much needed treatment to PSC patients.

We're also seeing excellent momentum on our VANTAGE PBC and EXPAND studies, and are looking forward to starting our Phase 2 study of MRM-3379 and 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, and an exciting pipeline.

With that, I'll hand it 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 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 US, LIVMARLI demand remains strong with Alagille syndrome and PFIC with approximately $57 million in net product sales for the quarter. Notably, we're 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 diagnosis 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, adolescence, 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 medications 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 US launch of the single tablet per dose formulation in June as meaningful convenience for patients. So 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 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 a strong performance from our bile acid portfolio with CTEXLI and CHOLBAM 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 US. 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 studies, we believe LIVMARLI ultimately has the potential to be a $1 billion-plus revenue grant. We're excited about continuing to execute to realize that potential, prepare for potential launches ahead out 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 [PTSD]. The last patients are in screening now, keeping us on track to complete enrollment this quarter and on track for expected topline 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 end points with the FDA in a pre-ID meeting earlier this year and our IND has recently cleared. We are on track to initiate the Phase 2 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 full blind placebo-controlled study evaluating three 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 Phase 3.

We're excited by the pace and engagement across our pipeline. I look forward to sharing further updates on the coming quarters. I'll now hand the call over to Eric to discuss our financial results for the quarter. Eric?

Thanks, Joanne, and good afternoon, everyone. We the 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 medicine.

Total operating expense for the quarter as of June 30 was $133 million, which includes R&D expense of $46 million, SG&A expansion of $63 million, and cost of sales of $23 million. Expenses for the quarter included non-cash stock-based compensation expense of $18 million and intangible amortization and other non-cash items of $6 million. The intangible amortization and other non-cash items expense are largely reflected in our cost of sale.

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 margin continued to improve. For example, our cash contributions margin from our commercial business exceeded 50% in the second quarter. Cash, cash equivalents, and investment worth $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.

Thank you, Eric. 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 medicine 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.

With that, operator, please open the call for questions.

(Operator Instructions) Gavin Clark-Gartner, Evercore.

Hey, guys. Congrats on another great quarter. First, I just wanted to ask on LIVMARLI. What are you seeing for overall therapy persistent 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 with expectations, baseline characteristics continuing to come in as expected or anything else you can give us there would be really helpful thanks.

Thanks, Gavin, for the question. I'll let Peter speak to the persistence question and I'll let Joanne comment a little bit about how this conduct is going.

Yeah, thanks for the question, Gavin. In terms of persistence, our information is most stable from the Alagille indication where we've got patients about several years or some approaching a decade, and think about persistence by 70% to 75% are on after one year, so that's the kind of attrition in year one and then in subsequent years, the attrition is much less than that. So that's probably the way to think about Alagille and PFIC is just probably a bit too early to comment.

Hey, 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 of the standard deviation should come in less than that, so given that powered the study, assuming a treatment of 1.75 with a division 3, probably it's closer to.

So I think that gives us some 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 screening.

Jessica Fye, JPMorgan.

This is [Abdullan] 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? Thank you.

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 here today, 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 and that $490 million to $510 million range.

Ryan Deschner, Raymond James.

Thanks, and congrats on the quarter. Wanted to ask what main drivers are you attributing to the growth that we're seeing with LIVMARLI sales? And then also how meaningful an impact on script volumes? Are you saying specifically due to the availability of the tablet format for LIVMARLI? Thank you.

Thanks for the question. I'll give a first comment and let Peter add on to it. I think one of the several dynamics going on here, I think one, in general that we've noticed it's really just as PFIC has been added in the US building awareness of availability of genetic testing and the concept of later onset of PFIC diagnosis, which to be honest, when we got the label expansion and we initially starting out in PFIC, we thought it was pretty minimal, what we're finding is that it's more -- they're 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.

Yeah, I think that is one of the main drivers really growing the pipe 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 businesses 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 outside of that didn't have an effect this quarter, but certainly encouraged. I've had a lot of positive feedback from, patients and providers who chosen to go to the tablet since then.

Brian Skorney, Baird.

Hi, this is Luke on for Brian. Thanks for taking the question. 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?

Yeah, thanks for the question, Luke. As far as inventory, it's really only relevance, and insofar as Japan and Takeda goes, no inventory in the business in the US or Europe. Takeda is large periodic orders that happened and 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 some (inaudible) estimate can change, but that's kind of the best color we give to you. We expetc quarter-to-quarter variability there.

Yeah, specifically in Q2 there's $11 million with the number of the Q2 number.

Mike Ulz, Morgan Stanley.

Good afternoon. Thanks for taking the question and congratulations on the quarter as well. Maybe just a question on Fragile X, 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? Thanks.

Yeah, thanks for the question. So we're actually good to go. We have the clearance from the IND so we have a study you may proceed letter, we've engaged a lot with the patient community and also the physician community, make sure we incorporate 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.

Mani Foroohar, Leerink Partners.

Hey, guys, you have Ryan on for Mani. Congrats on the quarter. Just curious how well-penetrated 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? Thank you.

Yeah, thanks for the question. I can touch on the last point first and then pass over to Peter to talk about some of the sizing for the various components for LIVMARLI. In terms of the Phase 2 precedent data from the Shionogi program in the upcoming Phase 3, it couple of thoughts that we have on it, first to phase two is great proof of concept out there and kind of what got us excited about 3379 and the ability to have potentially wider therapeutic index, get more of the drug into the CNS.

And in terms of kind of what we are looking for at the Phase 3, the effect of that differentiated profile that we have, I think kind of makes us really interested to run our proof of concept and 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.

Yeah. And in terms of your question about penetration and opportunity, if you think about the US, Alagille syndrome, we think we're approaching 50%, penetration, but, still every quarter including Q2, adding patients and both infants as well as kind of older patients who are more prevalent in in that prevalent addressable pool so still see the potential to keep growing all you further and further, in subsequent quarters as we And grow that that business. Pic is, been really interesting I Chris mentioned his comments were growing the pie right now as we speak.

I think traditionally, the field and others in the area thought about, Pic is really an infant onset disease and if if it's not that scenario, then it's not P&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 to kind of how big that could be. I think, historically we thought about PI as being about 3 of Alio, quite frankly, that's probably an underestimate at this point, so decided to to find that as forward.

And then add on, the one other component of when you think about the total amount of marley potential billion plus number that we're looking at the expand study also is a big contributor there where they 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 with patients on therapy and ultimately the size of the brand. Awesome, appreciate the call. Yeah, that's a question.

Josh Schimmer, Cantor Fitzgerald.

Thanks very much. Once I be on the expand study. I was wondering if you could share if any of those eligible patients already on the Mali through Compassionate E or other exceptions.

Yeah, thanks for the question. I'll let Joanne speak a little bit to the background of how we thought, came upon designing the expand studies kind of speaks to that question.

Yeah, thanks for the question. So, really the expense that came around because we had a lot of requests for passionate abuse in these patients with pothetics, from these other settings and so, we're taking patients who have not previously been treated in order to assess their treatment response in this setting. So far we're encouraged by the engagement we've heard from sites and also, just the interest from patient populations as well. Thanks for the question.

David Lebowitz, Citi.

Thank you for taking my question. I know a few years ago, $500 million was you as kind of the the peak for for Marley, this is obviously a dramatic shift. How much of it comes from potential from the new indications, versus Pic and ALGS. New potential I think so.

Yeah, 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 allergy in the US is kind of the market sizing, so this is going to, first time with these indications that we put out guidance on where we think that Marli can ultimately get to, so slightly different lens than kind of in the 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 three indications, And a band in the US, 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 and things that we're doing directly as well as distributors and partners and the success that they're seeing.

Got it. Thanks for taking my question. Yeah, thanks for the question.

Jonathan Wolleben, Citizens.

Hey, thanks for taking the question. Two for me. One on PC with active pruritis and 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 puritus in that group. And then, second one, just wondering on CTX if you guys have seen any inflection that you can promote and what do you expect for that long term. Thanks.

Yeah, thanks for the question. I'll pass this over to Peter and Joanne to speak to the two component them Peter lead off with the CPS.

Yeah, we're certainly, excited about the FDA approval now, for full quarter, sent 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, and CS pa patient finding is Laborious but excited about the potential there, to grow this longer term.

Yeah, thanks for the question. Regards to PSC, we do think that, bile acids do have a role here. However, the path physiology is a bit different than some of the other diseases like algae on Tic that we studied in the past, in reality, what we're treating is cold stasis, and therefore, there's an intrapatic component to it that we don't measure.

What we think is that the, what we're measuring in serum bio acids is really kind of spill over. And so we think that the serum bio acid is probably less important when we're thinking about a disease like PSC, probably more important when you're thinking of, allergy teeth, for instance. So like, slightly different disease, pathophysiology, but still kind of important central feature here is cold stasis.

Swayampakula Ramakanth, H.C. Wainwright.

Thank you, thanks for taking my questions. I have two of them. The first one being on Marley, so you made some remarks regarding how tea is managing the Japanese part of the the collaboration, any remarks on how you're going about in Europe. And, it also it became what sort of efforts are you making to increase your penetration. So that's question number one on the question number two is on the, based on the expand study, what sort of additional population patient population can you bring to live morally. Thanks.

Great, thanks for the question. I can make a couple comments on kind of in market, Marli and then Peter speaks to the opportunity and expand and the commentary on Europe and kind of where we're at, but I'd say is, European performance to date is largely allergy syndrome, so that kind of what's to come and the most exciting in some of our direct European markets is now bringing forward the Pic 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.

Yeah, and in terms of expanding, a lot of different ultra rare, patient populations individually when you look at the underlying kind of etiology of cause of the cosacris that that could, that could pull in certainly biliaryresia patients with coritis will be a portion of that, but there are also some others and we hear about these as as Joan mentioned earlier through Compassionate access requests. And from sites who have these patients in their clinic and they don't have anything to offer them so excited about the potential to to study them and potentially have an option.

Thank you. And that was the final question. So this concludes the Q&A portion of today's call. So we'll hand back over to Chris Peetz for any final comments.

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

That concludes today's call. Thank you, everyone, for joining. You may now disconnect. Have a great day.