Mirum Pharmaceuticals, Inc.

Hello, everyone, and welcome to the Neuron Pharmaceuticals Report Second Quarter 2025 Financial Results and Provide Business Update. My name is Carla, and I will be coordinating your call today. During the presentation, you can register to ask questions by pressing star followed by 1 on your telephone keypad. If you change your mind, please press star followed by 2. I would now like to hand you over to your host, Andrew McKeegan, SVP of Strategies 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 Miriam Pharmaceutical's second quarter 2025 conference call. I'm joined today by our CEO, Chris Peets, our President and Chief Operating Officer, Peter Radovich, our Chief Medical Officer, Joanne Kwan, and Eric Bjerkel, our Chief Financial Officer. Earlier today, Miriam issued a news release announcing the company's results for the second quarter 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 Merrim'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 10Q and subsequent SEP 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 Barron, the second quarter that underscores the momentum behind both our commercial medicines and our pipeline. Barron was founded in 2018 with a vision of bringing life-changing medicines to patients with rare disease around the world. Today, we have three approved medicines with reimbursed patients in over 30 countries, a pipeline that is rapidly advancing opportunities in 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 premiering with total revenues reaching $128 million, or 64% growth over the second quarter last year. But Marley is a key driver of these results and is continuing to bring substantial benefits 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 of guidance for 2025 to be $490 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 VISTA's Phase 2B study and primary sclerosynchronegitis, PFC, 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 IDOT inhibition across other cholestatic settings gives us confidence in the potential of felixidat and PFC. Exciting steps lie ahead to potentially bring this much-needed treatment to PFC patients. We're also seeing excellent momentum in our VantagePVC and EXPAND studies and are looking forward to starting our Phase II study of MRN3379 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 congratulations Thank you to the Miriam 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 Miriam, with total net product sales of approximately $128 million. driven by the continued momentum across Lidmarly in both the United States and international markets, as well as solid performance from our bile acid portfolio. In the U.S., Lidmarly demand remains strong in algeol syndrome and PPIT, with approximately $57 million in net product sales for the quarter. Notably, we are seeing more PPIT 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, 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 Allerheal Syndrome and PVEC indications with providers increasingly viewing Livmarly as a preferred treatment across these settings of pediatric cold stasis. 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 with Marley 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 Lidmarly in June with promising demand observed in the initial days of commercialization. Under our license agreement with Takeda, we received large periodic orders for Lidmarly, creating quarter-to-quarter variation in international product sales. We also saw strong performance from our vial asset portfolio, with Cetexly and Colbon contributing approximately $40 million in revenue. These medicines continue to benefit from steady demand and increased engagement following the Cetexly approval earlier this year. Given the momentum across our medicines, we are raising full-year revenue guidance to $490 to $510 million, driven largely by Lidmarli's strong performance, particularly growth in our international business, steady increase in allogeal demand, and our PFIT launch in the U.S. It's an exciting time for realizing Liv Marley's potential. Looking long-term, with the current trends in allogeal syndrome and PFIT, and the label expansion opportunity in ultra-rare cholestasis we aim to unlock through the expand study, we believe Liv Marley 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 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 the Lixabat, we're very encouraged by the momentum in our VISTA 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 live marling and 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 MRM3379, 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 need for new therapy. This is a randomized, double-blind, placebo-controlled study evaluating three active doses in order to identify the optimal dose. An additional open-label cohort will include approximately eight younger patients, males age 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 world-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 three. We're excited by the pace and engagement across our pipeline and look forward to sharing further updates in the coming quarters. I'll now hand the call over to Eric to discuss our financial results for the quarter.

Eric? Thanks, John, 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 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 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 Miriam 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 Miriam. 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.

Sure. We will begin now the question and answer session. If you'd like to ask a question, please press star followed by one on your telephone keypad. If you change your mind, please press star followed by two. When preparing to ask your question, please ensure your device is muted locally. And our first question comes from Gavin Clarkartner with Evercore.

Hey guys, congrats on another great quarter. First, I just wanted to ask on Liv Marley, 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 VISTA 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.

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

Thanks for the question, Gavin. In terms of persistence, our information is most stable from the allergial indication where we've got patients about several years or some of them approaching a decade. And, you know, if you think about persistence, probably 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 it now is, you know, an NPVIC 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, you know, we're feeling pretty confident. And part of it is that the standard deviation that we powered the study on was pretty conservative. So, you know, our best estimate is that the standard deviation should come 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, you know, some good confidence kind of proceeding forward as we're getting the last patients in and screening.

Great. Thank you.

Thank you. The next question comes from Jessica Farb with JP Morgan.

Hi, this is Abdul for Jess. Congrats on the quarter. Can you provide details on the expected revenue distribution between Liv Marley and the bioasset 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 in the 4.9, even 5.10 range.

Thank you.

Thanks for the question. Thank you. The next question comes from Ryan Dashner with Raymond James.

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

Thanks, Ryan, for the question. give a first comment and let Peter add on to it. I think one of the – there's 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, you know, the concept of later-onset PFIC diagnoses, which, to be honest, when we, you know, got the label expansion and we're initially starting out in PFIC, we thought was pretty minimal. What we're finding is that 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.

Yeah, I think that's a – that is one of the main drivers, really growing the pie in PFIC, if you will, the total, you know, market for the class in that setting. Also happy with the continued growth in algeol syndrome, and certainly, you know, the international business has performed well. In terms of your question about the tablet, you know, that was introduced in the month of June. So, obviously, as part of our comments there, the outset of that didn't have an effect this quarter, but certainly encouraged, had a lot of positive feedback from patients and providers who have chosen to go to the tablet since then.

Thanks for the question, Ryan.

Thank you. So, the next question comes from .

Hi, this is Luke on for Brian. Thanks for taking the question. To Marlee, can you discuss any inventory impacts in the second quarter? And also, could you provide a little more insight on the cicada order cadence? Do you expect it to be more of a seasonal trend, or would it be more regular than that?

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

Yeah, specifically in Q2, 11 million was the number, the Q2 number. Great. Thank you. Thanks for the question.

Thank you. The next question comes from Mike Oles with 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 from the FDA or any next steps before you start that study in the fourth quarter. Thanks.

Yeah, thanks for the question. So, you know, we're actually good to go. We have the clearance from the IND, so we have a study may proceed letter. You know, we've engaged a lot with the patient community and also the physician community to make sure we've incorporated their comments into the design of this 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.

Great. Thank you.

Thanks for the question.

The next question comes from .

Hey, guys. You have Ryan on for Mani. Congrats on the quarter. Just curious how well-penetrated do you guys think you are in the Aligil and PFIC markets? Kind of looking at your commentary that Livmarly can be a billion-dollar product, wondering how you see that broken out by Aligil 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 Shia Nogi's update later this year? Thank you.

Yeah, thanks for the question. I can touch on the last point first and then pass it over to Peter to talk about, you know, some of the sizing for the various components for Live Marley. In terms of, you know, the phase two precedent data from the Shinogi program and the upcoming phase three, a couple of thoughts that we have on it. You know, first, the phase two is great proof of concepts 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, you know, kind of what we are looking for out of the phase three, It's 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. In fact, we're not going to learn a lot from any top-line release, but, you know, 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., you know, in allogeal syndrome, we think we're approaching 50% penetration, but, you know, still every quarter, including Q2, you know, adding patients and both infants as well as kind of older patients who are more prevalent in that prevalent addressable pool. So, you know, still see the potential to keep growing allogeal further and further in subsequent quarters as we have and grow that business. PPIC 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, you know, PPIC is really an infant onset disease, and if it's not that scenario, then it's not PPIC. 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. We have kind of less visibility to kind of how big that could be. I think, you know, historically, we thought about PVIC as being about a third of algeol. Quite frankly, that's probably an underestimate at this point. So, we decided to define that as moving forward.

And then, I'd add on, you know, the one other component of when you think about the total of Marley potential, the billion-plus number that we're looking at, the EXPAND study also is a big contributor there, where the EXPAND patient population is, you know, really at least the size of PFIC and, you know, that kind of 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. Awesome. Appreciate the call. Yep. Thanks for the question.

The next question comes from Josh Schumer with Contour Fitzgerald.

Thanks very much. One from me on the EXPAND study. I was wondering if you could share if any of the eligible patients are already on the SMARLY through compassionate use or other exceptions.

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

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

The next question comes from David Lebowitz, Babe City.

Thank you for taking my question. I know a few years ago, 500 million was viewed as kind of the peak for Liv Marley. This is obviously a dramatic shift. How much of it comes from potential from the new indications versus PFIC and ALGS? New potential indications.

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 allogeal in the U.S., just kind of the market sizing. So this is the first time with these indications that we put out guidance on where we think that Marley can ultimately get to. So it's 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 three indications, the power shield piece that can 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. Got it.

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

So, just as a reminder that if you'd like to ask a question, you start one on your telephone keypad. The next question comes from Jonathan with Citizens.

Hey, thanks for taking the question. Two for me. One on PSC. You guys estimate that there's, you know, 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? Thanks.

Yeah, thanks for the question. I'll pass this over to Peter and Joanne to speak to the two components and let Peter lead off with the CTX.

Yeah, you know, we're certainly, you know, excited about the FDA approval now. First full quarter since that year, you know, a lot of our efforts are on patient finding across different specialties where, you know, patients present. Not expecting, you know, I think it's a gradual steady build in CTX. Patient finding is laborious, but excited about the potential there to grow this long-term.

Yeah, thanks for the question. Regards to PSC, you know, we do think that vial acids do have a role here. However, the pathophysiology is a bit different than some of the other diseases, like algae and metific that we've studied in the past. In reality, what we're treating is cholestasis, and therefore, you know, there's an intrapatic component to it that we don't measure. What we think is that what we're measuring in serum vial 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, you know, . So, I think, you know, slightly different disease pathophysiology, but still kind of the important central feature here is cholestasis.

Interesting. Okay. All right. Thank you. Thanks for the question.

So, the next question comes from .

Thank you, and thanks for taking the questions. I have two of them. The first one being on . So, you know, 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 in between 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 live morally? Thanks.

Great. Thanks for the question. And I can make a couple comments on kind of in-market Marley, and then Peter speaks of the opportunity and expand. And, you know, commentary on Europe and kind of where we're at, what I'd say is, you know, European performance to date is largely eligible. So kind of what's to come and most exciting is 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 expanding?

Yeah, and in terms of expanding, you know, a lot of different ultra-rare patient populations individually when you look at the underlying kind of etiology of cause of the colic arthritis that that could pull in. Certainly, biliary atresia patients with colic arthritis will be a portion of that. but there are also several others. And, you know, 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, you know, the potential to study them and potentially have an option.

Thank you. Thanks for taking my questions.

Thank you.

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

Great. Thanks again for joining us today. Hey, after you continue to support, we look forward to updating you in the course. Have a great afternoon.

This concludes today's call. Thank you, everyone, for joining Human Apps Connect. Have a great day.