MIRM - NASDAQ

Hello, and welcome to Mirum Pharmaceuticals Reports Fourth Quarter and Year-End 2024 Financial Results and Provides Business Update. My name is Elliot, and I'll be your coordinator today. [Operator Instructions] I would now like to hand over to Andrew McKibben, Senior Vice President of Strategic Finance and Investor Relations. Please go ahead.

Thanks, Elliot, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals' fourth quarter 2024 conference call. I'm joined today by our CEO, Chris Peetz; our Chief Medical Officer, Joanne Quan; and Eric Bjerkholt, our Chief Financial Officer. Peter Radovich, our President and Chief Operating Officer, could not be with us today as he's at an international launch event in Europe this week. Earlier today, Mirum issued a news release announcing the company's results for the fourth quarter and full year 2024. 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 will 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 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-K 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. I'm excited to start today's call with a recap of Mirum's achievements over the last year and share an update on our strategic goals for 2025. In the short time since our founding, through our focus on bringing important medicines to patients, we have created a strong business in ultra-rare disease that is cash flow positive with an attractive pipeline and broader patient populations. We are still early in our journey and we firmly believe that the best is yet to come. Our strategic priorities over the next two years are to: one, further the global growth of our commercial medicines, highlighted by LIVMARLI's continued Alagille syndrome expansion, early PFIC success, and the recent approval of CTEXLI for cerebrotendinous xanthomatosis, or CTX, in the US; two, advance our high-impact pipeline, driving Volixibat to potentially pivotal data in adult cholestasis next year, initiating our Fragile X program for MRM-3379 and completing enrollment of the EXPAND study for LIVMARLI in cholestatic pruritus; three, selectively pursue product acquisition and license opportunities in rare disease with potential for significant patient and -- patient impact and value creation, just as we have since the launch of Mirum; and four, accomplish all of the above with continued scientific and financial discipline. 2024 was a big year for delivering on strategic goals. Total net product sales were $336.4 million, exceeding the upper-end of our revised guidance range. LIVMARLI finished the year with total net product sales of $213 million, including approximately $155 million from our US business and $59 million internationally. In the second half of last year, PFIC new patient starts and international uptake were drivers of the step-up in growth. We believe the strong demand we are seeing for LIVMARLI in Alagille syndrome and PFIC will continue. Beyond LIVMARLI, we also saw healthy growth in our bile acid medicine. We think we are starting to bend the curve here with total 2024 net product sales of $123 million. I'm also happy to say that, last week, the FDA approved CTEXLI, which is our new brand name for chenodiol for CTX in adults. With this approval comes seven years of work on exclusivity and the opportunity to begin promotional efforts with our current field team to reach patients in this under-diagnosed condition. Ultimately, the robust growth dynamics across all of our medicines positions us well for 2025 where we expect to add close to $100 million to our top-line, with anticipated net product sales between $420 million and $435 million for the year. 2024 was also a significant year for our pipeline. We expanded LIVMARLI's label with its approval for PFIC in both the US and Europe. We initiated the Phase 3 EXPAND study of LIVMARLI in broader settings of cholestatic pruritus, a significant growth opportunity for the brand. And beyond LIVMARLI, we achieved positive interim results for Volixibat in both VISTAS PSC and VANTAGE PBC studies, resulting in breakthrough designation in PBC. And finally, we have expanded our pipeline with the addition of MRM-3379 for Fragile X syndrome. This is another high unmet need orphan setting that aligns well with the capabilities we have built in rare genetic neurology for the launch of CTEXLI. Pulling all this together, we are set up for an exciting 2025 and beyond with continued strong execution in both our commercial business and pipeline of potentially high-impact medicines. And with that, I'll turn it over to Joanne to give a brief update on the pipeline. Joanne?

Thanks, Chris. 2024 was a highly productive year for our clinical programs, and I'm excited to continue this momentum into 2025. Starting with our three potentially registrational studies of our IBAT inhibitor, LIVMARLI and Volixibat, I'm pleased to say that the progress we made in 2024 builds further confidence in the impact of this mechanism on cholestatic pruritus. Across multiple settings, including Alagille syndrome, PFIC, biliary atresia, PSC and PBC, we've now seen clinical evidence for the potential of IBAT inhibition to have a pronounced impact on this debilitating symptom. Starting with Volixibat in PSC, recall that the VISTAS study is currently enrolling with a single active dose, 20 milligram BID, versus placebo, based on the blinded interim analysis we conducted in June of last year. Following the positive interim analysis, where we passed both the efficacy and safety thresholds for continuation, we've had great engagement from investigators and patient communities, and we are pleased with the continued progress in this study. We are on track to complete enrollment in the second half of this year, and given that this is a 28-week study, expect topline results in 2026. There are no approved treatments for PSC, and we look forward to another opportunity to work with global health authorities to bring a high-impact medicine to an underserved patient community globally. Turning to PBC, enrollment in the VANTAGE study is also progressing well, and we remain on track to complete full enrollment in 2026. Given the results of our interim analysis, where we showed a statistically significant, rapid, sustained improvement in pruritic versus placebo, we have seen a positive response from the investigator and patient community. Majority of PBC patients are able to maintain a good biochemical response with first-line UDCA treatment, but do not have adequate options to address their symptoms. The strength of the VANTAGE interim results in both first-line and second-line patients positions Volixibat to be a potentially impactful treatment option for a large proportion of patients with PBC. The breakthrough therapy designation we received from FDA last year acknowledges the importance of Volixibat as a potential treatment option. We are also excited about Phase 3 EXPAND study of LIVMARLI. This is an excellent opportunity to expand the label for LIVMARLI to include additional settings of cholestatic pruritus, where there's a clear need for an approved, effective treatment, and we are encouraged by the enthusiasm we are seeing from investigators. The study is ramping up well, and we are on track to complete enrollment in 2026. Shifting to MRM-3379, our new PDE4D inhibitor for Fragile X syndrome, we are preparing to initiate a Phase 2 study this year following discussions with the FDA. As a reminder, this mechanism has demonstrated proof of concept in Fragile X, and given the high expression of PDE4D in the brain and importance of this pathway in learning and memory, we believe MRM-3379's brain penetrant profile is potentially differentiating. In summary, we're very happy with the continued momentum of all of our clinical programs and the active engagement we foster with investigators and patient communities. I look forward to providing further updates on our progress during the year. I'll now turn it over to Eric. Eric?

Thank you, Joanne. I'm pleased to say that we are in an excellent financial position, supported by our strong performance in 2024, which I will now briefly summarize. 2024 was another year of continued strong growth in net product sales of our three commercial medicines. Total net product sales in the fourth quarter 2024 was $99.4 million compared to $69.5 million the year before, representing a 43% year-over-year increase. For the full year 2024, total net product sales were $336.4 million compared to $178.9 million in 2023. For LIVMARLI, total net product sales in the fourth quarter 2024 was $64.1 million. Total LIVMARLI net product sales for 2024 was $213.3 million, representing a 50% increase compared to 2023. Turning to our bile acid medicines, total net product sales in the fourth quarter 2024 were $35 million, representing an approximately 25% growth over the fourth quarter of 2023, the first full quarter the portfolio was under [indiscernible]. Total net product sales for the portfolio for all of 2024 was $123.1 million. Total operating expense for 2024 was $424.5 million, which includes R&D expense of $140.6 million, SG&A expense of $202.2 million and cost of sales of $81.6 million. Expenses for the year included non-cash stock-based compensation expense of $48.4 million and intangible amortization and other non-cash items of $31 million. This intangible amortization and other non-cash items expense is largely reflected in our cost of goods sold. In the fourth quarter and full year, R&D expense also reflected the $7.5 million upfront payment we paid to Enthorin for the MRM-3379 license. When adjusting for the non-cash items, I'm happy to say the business was cash flow positive in 2024, and we expect this to continue this year. We ended 2024 with cash, cash equivalents and investments of $293 million, an increase of approximately $7 million from the start of the year. Looking ahead, we expect net product sales of $420 million to $435 million in 2025, and we are guiding towards positive cash flow again this year. We are well funded, and we have the resources to execute on our plans and progress toward our multiple upcoming pipeline catalysts. Now, I'll turn the call back over to Chris for final comments.

Thanks, Eric. 2025 is set to be another big year for Mirum. With industry-leading commercial execution and advancing pipeline and a disciplined operating model, we have built a leading rare disease company, one that is positioned for sustained growth in the years to come. I'm proud of what we have accomplished and excited for the opportunities ahead as we continue to deliver life-changing medicines for patients and their families. And with that, operator, please open the call for questions.

Thank you. [Operator Instructions] First question comes from Gavin Clark-Gartner with Evercore ISI. Your line is open. Please go ahead.

Hey, guys. Congrats on the great progress. So, I just had one more strategic question. I know that you aren't able to call for redemption of convertible notes until next year, but just bigger picture, as your stock has traded well above the conversion price, the back of really strong earnings performance, pipeline advancement, does this all change how you think about BD and capital allocation in general? Thank you.

Thanks, Gavin, for the question. I'll make a first comment there and ask Eric to add anything else on the balance sheet. The thing I'd point out kind of the dynamic behind what you're pointing out there is that we've been able to navigate Mirum to a really unique position, particularly in this market backdrop for rare disease where we can take advantage of our financial position and performance to acquire and basically roll up some of these rare disease products that we see as great value-creation opportunities for the company. And I'll ask Eric to speak more specifically to the financing plans.

Yeah, thank you. The convert matures in four years, so that doesn't really factor into our plans meaningfully. I think our financial and financing flexibility as we continue to progress the business is significant and gives us a lot of flexibility to consider BD alternatives that we might find attractive.

Thanks for the question, Gavin.

We now turn to Jessica Fye with JPMorgan. Your line is open. Please go ahead.

Hey, guys. Good afternoon. Thanks for taking my question. I was hoping you could talk about the underlying assumptions like market penetration or share, potential competition, et cetera, that are behind the $1 billion revenue potential for MRM-3379 in Fragile X. And I guess, while we're talking about that asset, are there any other indications with the mechanistic rationale that could make sense to pursue? Thank you.

Thanks for the question, Jessica. I'll speak to the market sizing and then have Joanne kind of comment about applicability of the mechanism in other settings. And quite simply, the way to think about the market potential, when we look at just male patients with Fragile X, it's a 50,000-patient market. So, a lot of different ways that you can look at the assumptions to see that the total addressable market is $1 billion or more quite easily. So, really, when we talk about that number, we're looking at the US opportunity. Do see substantial upside beyond that number even. It's a pretty simple kind of watermark to put there. And Joanne, you want to comment about...

Yes. So, actually I think, Jessica, you sort of kind of rightly kind of asked the question in terms of what other opportunities. We know that PDE4D is highly expressed in the brain in areas where learning and memory are very important. And so, there are a wide number of conditions that this could be -- you could envision this could be used for. The way we're really approaching this is to kind of use Fragile X as our kind of first entry point, conducting a proof of concept there, identifying a dose. And then, once we have that, then I think it opens up the possibility for entering into some other indications associated with intellectual disability. So, certainly a lot of potential there that we're excited to access.

We now turn to Mani Foroohar with Leerink Partners. Your line is open. Please go ahead.

Hey, guys. You have Ryan on for Mani. Thanks for taking our question. So, I'm curious, when you look at the Alagille market, where do you think we are in terms of penetration into the prevalent population? And kind of going forward, is US growth really going to be driven more by new diagnoses or kind of greater penetration into those that are not on IBAT yet? Thanks.

Thanks, Ryan, for the question. In terms of overall penetration for the eligible treatment population in the US, so Alagille syndrome patients with pruritus that are pre-transplant, we're probably in the range of 40% or so penetrated. So, just from that statistic alone, we see a lot of growth potential in the prevalent patients. And think about what's driving that growth over time, there are actually several tailwinds on that. One is just the further penetration into the prevalent population. There's continued new diagnoses that come along the way, so new patients entering. They're usually infants, so they're generally lower dose patients, but there are new patients that are diagnosed and start each year. And then, behind that, this is weight-based dosing, so you do see some of those dose adjustments over time. So, all of that kind of combines for the US to show that there's a long runway of continued growth for Alagille syndrome in the US.

We now turn to David Lebowitz with Citi. Your line is open. Please go ahead.

Thank you very much for taking my question. In terms of the recent approval for CTX, congratulations on that. Could you, I guess, elaborate on how you expect this could affect the sales trajectory on this point going forward, given there's already use in that particular population?

Thanks for the question, David. Yeah, so your kind of understanding in your question, the dynamic here where we already have -- we think that there's substantial number of the diagnosed CTX patients have been on chenodiol. The plan is to have those convert over to CTEXLI in the coming months. And the goal here is to impact diagnosis and getting more patients diagnosed and then to treatment. So, we do expect it to be a gradual kind of bending of the curve of bringing new patients to diagnosis earlier and preventing the accumulation and buildup of some of these irreversible effects of the disease.

Got it.

Thanks for the question.

Our next question comes from Mike Ulz with Morgan Stanley. Your line is open. Please go ahead.

Hi. This is Rohit on for Mike. Thanks for taking our questions. Can you just talk about the patient mix between Alagille syndrome and PFIC for LIVMARLI in fourth quarter of '24 and how you expect this to play out in 2025? And then additionally, how many of the patients on the PFIC expanded access program are now on paid drugs? Thank you.

Thanks for the question, Rohit. I'll touch on the last one there first. During the year, last year, we were able to convert all of the US expanded access patients over to commercial products. So that was complete, really most of it into the third quarter last year. And in terms of the patient mix, we don't post specific numbers. But throughout kind of where we stand today, most LIVMARLI patients by far are Alagille syndrome patients. So that's the vast majority of the contribution today. In terms of new patient starts, since really Q3 of last year, we have seen -- with the steady Alagille patient starts, we have seen a nice step-up in PFIC patient starts. So, they are contributing quite substantially to new patient starts going forward, and you see that reflected in the top-line performance.

Thank you.

Thanks for the question.

We now turn to Ryan Deschner with Raymond James. Your line is open. Please go ahead.

Hi, there. Congrats on the quarter. My question is, how much commercial team expansion would you anticipate doing for expanded pruritus in ultra-rare cholestatic patients, pending the result of the Phase 3 EXPAND study? And then, I have a quick follow-up.

All right. Thanks for the question, Ryan. Looking at planning for LIVMARLI's potential label expansion with EXPAND, we anticipate that's largely the same prescribing universe as the Alagille syndrome and PFIC prescribers. So, it wouldn't be an expansion of the field team that's already in place. So, a lot that we can leverage there commercially. And you said you had a follow-up question.

Yeah, thanks. Do you feel at this point -- do you have a feel at this point for how many -- specifically, how much of an impact the growing average patient weights are impacting sales growth in Alagille? How big actually is this growth component now compared to some of the other tailwinds here? And how do you expect it to grow moving forward?

I mean the way that I would describe it is we look at and kind of think about this is the average dispense. And it changes quite modestly over time, in part because you have -- we continue to have new diagnoses come in. So, there are new infant patient starts along the way. That kind of tempers the overall effect. But we have seen it kind of gradually increase over the years.

Got it. Thank you very much.

Thanks for the question.

We now turn to Brian Skorney with Baird. Your line is open. Please go ahead.

Hi. This is Luke on for Brian. Thanks for taking the question. We were hoping you could just talk a little bit about how the VANTAGE study takes into account prior OCA use and enrollment. And do you think patients recently discontinuing OCA could see an impact on pruritus measurements as compared to a patient not discontinuing?

Thanks for the question. I'll let Joanne jump into that one.

Yeah, thanks for the question. So, when the study was started, we actually thought there would be a bigger contribution in terms of patients who are on OCA. It turns out it's really not an issue at this point. And so, that's -- our enrollment has actually picked up quite nicely since the interim results came out. We're not really seeing that there's an issue in terms of patients, a lot of patients coming forward with OCA who are candidates for the study otherwise. And I think that just reflects overall kind of usage patterns with OCA in general, not really that much of a contender in this space.

Yeah. Kind of in addition to that, recall that for PBC, the VANTAGE study, about two-thirds of those patients are first-line. So that would be before OCA would be kind of -- would have been used or before the new PPARs are used.

Thank you.

Thanks for the question.

Our next question comes from Jonathan Wolleben with Citizens JMP. Your line is open. Please go ahead.

Hey, thanks for taking the question. Just wondering, piggy backing on a prior EXPAND question, what do you envision the label looks like if you have success in that Phase 3 trial? And then, how do you wrap your heads around that 1,000 patient US and EU prevalence, given it's a collection of a bunch of small indications?

Jonathan, thanks for the question. The label -- the indication statement is something to nail down, frankly. It is -- as you point out, it's a definition somewhat of exclusion. It's a basket of several different causes of cholestasis, excluding PSC, PBC, ICP, Alagille syndrome and PFIC. So, it's all of the many less common causes of cholestasis. So, exact wording will need to be ironed out as we get to that label expansion. In terms of how we think about the patient number, though, we think it's -- quite simply the way to think about it, it's a PFIC-sized opportunity or larger. And as we looked at kind of real compassionate use requests and interest from physicians kind of counting up some of those patient numbers and where that demand was coming from, that's how we landed at that 1,000 patient estimate for the US and Europe. So, I feel it's a very tangible market estimate as opposed to maybe an epidemiology study, for example. So, I feel confident that it's a quite sizable opportunity for LIVMARLI.

All right. That's helpful. Thanks, Chris.

Thanks for the question.

And our final question comes from Ed Arce with H.C. Wainwright. Your line is open. Please go ahead.

Hello. Good afternoon, everyone. This is Thomas asking questions for Ed. Thank you so much for taking our questions. So first, for the Volixibat study in PSC, good to hear that it's on target to complete enrollment in the second half this year. Just wonder how many months or when should we expect to see topline data after complete enrollment is announced. If you can outline some details on the process?

Yeah, thanks for the question, Thomas. The simple way to think of it is it's an approximately six-month endpoint and time to close and clean the database. So kind of project some amount of time like that after enrollment completion. We do plan to announce enrollment completion when we get there.

Got it. And then, perhaps one question on the Phase 3 -- on the EXPAND study with LIVMARLI as well. Just wonder if you can share some patient experience that you have received to date and which type of rare cholestatic conditions are most common so far.

Yeah, thanks for the question. I'll maybe ask Joanne to speak to some of the data at AASLD last year on that point.

Yeah. We do actually have a number of patients that were treated through compassionate use for biliary atresia, and those results are quite strikingly positive for treatment of their pruritus. And of note, this is a different patient group than was studied in the earlier EMBARK study. So, these are biliary atresia patients that have likely had a Kasai when they were quite young, and then they continue on. We do know that over time, patients will progress in terms of their disease and often require liver transplant, and as part of that progression of the disease, they will develop pruritus. And so, we do have an abstract with a handful of cases where there's been quite good treatment outcomes using IBAT inhibition. So that's partly what gives us confidence in conducting a study like the EXPAND study that ultimately -- there is an unmet need and also that we do have a product that can really address that.

Understood. Perhaps one follow-up on that. Should we expect to see some kind of interim data from this study perhaps in medical conference posters?

Actually, we do not plan to do an interim analysis for the study. Our plan is to complete enrollment in 2026 next year. So, if any -- if we did an interim, it would actually slow things down. So, we do think we're on track to completing enrollment in 2026 and look forward to sharing the results when they're available for the full study.

Understood. Thank again for taking my questions.

Thank you.

Thank you, Thomas.

This concludes our Q&A. I'll now hand back to Chris Peetz, CEO, for any final remarks.

Great. Thank you all for joining us today, and have a great afternoon. Thanks.