Hello everyone and welcome to the Miran pharmaceuticals report second quarter 2025 financial results and provide business update. My name is Karla and I will be coordinating your call today. During the presentation you can register to ask questions by pressing star followed by one on your telephone keypad. If you change your mind, please press star followed by two. I would now like to hand over to your host, Andrew McKeven, SDP 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 Miriam Pharmaceuticals 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 Bierkel, 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 can be found in the Investor 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 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 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 MIRA, the second quarter that underscores the momentum behind both our commercial medicines and our pipeline. MIRA 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 20 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. On that note, on second quarter results, we're excited to share another strong update from Miram with total revenues reaching $128 million, or 64% growth over the second quarter last 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. dollars, 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 sclerosynchalongitis, PSC, is on track to complete enrollment this quarter, with top-line data expected in the second quarter next year. The VISTA program passed its interim analysis last year, and the consistent precedent data for IVAT inhibition across other cholestatic settings gives us confidence in the potential of felixabat and PSC. Exciting steps lie ahead to potentially bring this much-needed treatment to PSC patients. We're also seeing excellent momentum in our Vantage PBC and EXPAND studies and are looking forward to starting our Phase II study of MRN-3379 and Fragile X syndrome now that we have FDA feedback on the program, which Joanne will tell you more. Thank you to the Miram team, whose dedication to bringing high-impact medicines to patients has made all this progress possible. How this group has come together to create a high-growth, cash-flow-positive rare disease leader, is an exciting pipeline. 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 Miram, with total net product sales of approximately $128 million, driven by continued momentum across Livemarly in both the United States and international markets, as well as solid performance from our bile acid portfolio. In the U.S., Livmarly demand remains strong in allergial syndrome and PFIT, with approximately $57 million in net product sales for the quarter. Notably, we are seeing more PFIT patients than we had originally anticipated, which we believe is due in part to increase disease awareness and broader use of genetic testing, leading to more PFIT 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 Allergial Syndrome and Prefect Indications, with providers increasingly viewing libmarly as a preferred treatment across these settings of pediatric call spaces. 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 adds meaningful convenience for patients, though I'll note that Q2 results reflect the performance of our oral solution. Internationally, we are seeing durable Livemarly 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 Livemarly 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 BioLacid portfolio, with Setextli and Kolban contributing approximately $40 million in revenue. These medicines continue to benefit from steady demand and increased engagement following the Setextli 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 Livmarly's strong performance, particularly growth in our international business, steady increase in allergial demand, and our PFIT launch in the U.S. It's an exciting time for realizing Livemarly's potential. Looking long-term, with the current trends in Allergial Syndrome and PFIC, and the label expansion opportunity in ultra-rare cholestasis we aim to unlock through the EXPAND study, we believe Livemarly 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 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 felixabat we're very encouraged by the momentum in our vista study for patients with pruritus due to psd 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 livemarly in additional settings of cholestatic varitis 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 PDE-4D 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 2 study by the end of the year. Our study will enroll approximately 52 male participants, age 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 three active doses in order to identify the optimal dose. An additional open-label cohort will include approximately eight 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 CRYSTALIZE COGNITION COMPOSITE, A WELL-RECOGNIZED COGNITIVE MEASURE ALSO USED BY OTHER PROGRAMS IN THIS SPACE. BASED ON FDA FEEDBACK, WE DO ANTICIPATE THAT THIS ULTIMATELY WILL BE THE PRIMARY ENDPOINT IN PASE 3. WE'RE EXCITED BY THE PACE AND ENGAGEMENT ACROSS OUR PIPELINE. I LOOK FORWARD TO SHARING FURTHER UPDATES IN THE COMING QUARTERS. I WILL NOW HAND THE CALL OVER TO ERIC TO DISCUSS THE FINANCIAL results for the quarter. Eric?

Thanks, John, and good afternoon, everyone. We delivered another 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 and the june 30 was 133 million which includes rmd expense of 46 million sgma 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 six 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 percent 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 miram 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 Mira. 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.

We will begin now with 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 unmuted locally. And our first question comes from Gavin Clark Gartner with Evercore.

Hey, guys. Congrats on another great quarter. First, I just wanted to ask on Livmarly, 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, you know, 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 VISTA's 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 that have been on several years or some of them approaching a decade. And, you know, 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 as you own. And PFIC is just probably a bit too early.

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 uh was pretty conservative so you know 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 three probably it's closer to two so i think that gives us added confidence and i can also share with you that the baseline characteristics in general reflect the psd population so i think 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 into screening and completing it.

Great.

Thank you. The next question comes from Jessica Farb with J.P.

Hi. This is Abdulan for Jess. Congrats on the quarter. Can you provide details on the expected revenue distribution between Livemarly and the Biolass business for the remainder of the year?

Thanks for the question. And 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 that 490 to 590. Thank you.

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

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

Thanks, Ryan, for the question. I'll give a first comment and let's have Peter add on to it. I think one of the – and 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, 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'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 is one of the main drivers, really growing the pie in PFIC, if you will, the total market for the class in that setting. Also happy with the continued growth in Al-Ageel 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 outset didn't have an effect this quarter, but certainly encouraged. I've had a lot of positive feedback from patients and providers who have chosen to go to the tablets since then.

Thank you. So the next question comes from Brian Scorni with Bert.

Hi, this is Luke on for Brian. Thanks for taking the question. Two on with Marley, 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 look yeah as far as inventory it's really uh only relevant uh you know in so far as japan and toketa because there's no no inventory in the business in the u.s or europe anywhere else with toketa it is kind of large periodic orders uh that happened and uh from time you know from you know we expect there'll probably be another one this year but we don't have a perfect line of There's variable consideration placed on it when the order comes. So that's why, you know, in 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 out of the Q2 number. Great. Thank you.

The next question comes from Mike Oath 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've 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.

Yeah, thanks for the question. So we're actually good to go. we have a clearance on 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 they 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.

The next question comes from Mani Fullheart with Leering Partners.

Hey, guys. You have Ryan on for Monty. Congrats on the quarter. Just curious, how well penetrated do you guys think you are in the Alagil 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 Alagil 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. Thanks for the question. I can touch on the last point first and then pass over to Peter to talk about, you know, some of the sizing for the various components for libmarling. In terms of, you know, the Phase II precedent data from the Shinogi program and the upcoming Phase III, a couple of thoughts that we have on it. You know, first, the Phase Phase II is great proof of concepts out there in 3379 and the ability to have a potentially wider therapeutic index, get more of the drug into the CNS. And in terms of what we are looking for out of the Phase III, that differentiated profile that we have I think makes us really interested to run our proof of concept regardless of the outcome, 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 Allergy L syndrome, we think we're approaching 50 percent 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 alageal further and further. PPIC has, you know, been really interesting, as Ken and 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 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 study and patient population is, you know, really at least the size of PFIC and, you know, it's that kind of a 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. Appreciate the color. Thanks for the question.

The next question comes from Josh Schumer with Contour Fitzgerald.

Thanks very much. One for me on the EXPAND study, I was wondering if you could share if any of those eligible patients are already on this MARLI 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, you know, came upon designing the EXPANN studies that really kind of speaks to that question.

Yeah. Thanks for the question. So, you know, really the EXPANN study came around because we had a lot of requests for compassionate use in these patients with polystatic pariahs 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.

The next question comes from David Lebowitz, Bayt City.

Thank you for taking my question. I know a few years ago, $500 million was viewed as kind of the peak for Livmarly. This is obviously a dramatic shift. How much of it comes from potential from the new indications versus PFIC 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 alagil in the u.s just kind of a market sizing um so this is kind of the first uh first time with these indications that we put out guidance on where we think that marley can ultimately get to so 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 and expand in the US quite sizable what we're seeing on the international side also 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 success that they're seeing.

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 Boulogne with Citizen.

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 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 paritis 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 cta yeah you know 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.

Joanne. Yeah. Yeah, thanks for the question. In regards to PSC, you know, we do think that viral 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 viral 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, allergy lymphatic. So I think, you know, a slightly different disease pathophysiology, but still kind of the important central feature here is cholestasis.

Interesting.

So the next question comes from Suayam Pakula with H.C.

Thank you. Thanks for taking my questions. I have two of them. The first one being on Liv Marley. 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 within Europe, So what sort of efforts are you making to increase your penetration? So that's question number one. And the question number two is based on the EXPAN study, what sort of additional population, patient population can you bring to live morally?

That's great. Thanks for the question. I mean, I can make a couple comments on kind of in-market, MARLI, and then Peter speaks of the opportunity in EXPAN. And so commentary on Europe and kind of where we're at, what I'd say is European performance to date is largely algal 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 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.

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 colsac caritis, that that could pull in. Certainly, biliary atresia patients with colsac caritis 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 clinic and they don't they don't have anything to offer them so excited about the potential to study them thank you thanks for taking my questions and that was the final question so that does conclude the q a portion of today's call so i'll we'll hand back over to chris pitts for any final comments great thanks again for joining us today and for your continued support we look forward

to updating you in quarters ahead have a great afternoon this concludes today's call thank you everyone for joining Human Apps Connect. Have a great day.