Mirum Pharmaceuticals Inc (MIRM) 2023 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen. Thank you for joining today's Mirum Pharmaceuticals reports Q4 and year-end 2023 financial results and provides business update. My name is Tia, and I will be your moderator for today's call. (Operator Instructions)

It is my pleasure to pass the call over to Andrew McKibben, Vice President of Investor Relations and Finance. Please proceed.

Thanks, Tia, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals' fourth-quarter 2023 conference call. I'm joined today by our CEO, Chris Peetz; our President and Chief Operating Officer, Peter Radovich; our Chief Scientific Officer and Head of Research, Pam Vig; 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 fourth quarter and full year 2023. Copies of this news release and SEC filings can be found in the Investors section of our website.

Before we begin, I'd like to remind you that during the course of this call, we will be making certain forward-looking statements about Mirum and our programs based on management's current expectations, including statements regarding current and future business plans, development programs and regulatory expectations, strategies, prospects, market opportunities, and financial expectations.

Mirum is under no duty to update these statements, and they are subject to numerous risks and uncertainties. And actual results could differ materially from those results anticipated by these statements. Investors should read the risk factors set forth in Mirum's 10-Q for the quarter ended September 30, 2023, and in subsequent reports filed with the SEC.

With that said, I'd like to turn the call over to Chris. Chris?

Thanks, Andrew, and good afternoon, everyone. I'm excited to kick off an update on the many achievements for Mirum in 2023, another year of significant growth for us and cover highlights for what lies ahead for the company. Our continued progress in 2023 and opportunity ahead reflects the dedication of the Mirum team to making a difference in the lives of patients and their families around the world.

Over the year, we transformed our business with a broadened reach to patients in the US and internationally, achieving $179 million in net product sales and 142% year-over-year growth in total revenue. This was driven by continued strong growth for LIVMARLI and the expansion of our commercial portfolio with the acquisition and integration of CHENODAL and CHOLBAM.

We have now built a growing, self-sustaining, leading rare disease business that is positioned for a great 2024 and beyond. The last year has shown the value creation potential of our strategy to drive growth in our commercial medicines, unlock the potential of upcoming label expansion opportunities, leverage our expertise in cholestasis in adult settings, and continue to grow the pipeline.

Looking at the year ahead for execution on our strategy, overall, from the current commercial business, we expect to achieve $310 million to $320 million of net product revenue in 2024. This is expected to be driven by growth across all three commercially available medicines.

We also have multiple regulatory and clinical catalysts this year to advance our pipeline. For LIVMARLI and PFIC, we are on track for our PDUFA date on March 13. We're excited for the opportunity to bring the strong results of the March PFIC Phase 3 study to patients with the potential label expansion.

We're also preparing for the submission of the positive RESTORE Phase 3 results of CHENODAL and CTX in the first half of the year, an important label-enabling opportunity. And we've also made great progress with the VISTAS and VANTAGE studies for volixibat in PSC and PBC. Patients for the interim analyses have been enrolled, and we expect to conduct the dose selection interims of these adaptive studies in the first half of the year. We see the PSC program as an opportunity to bring the first-ever therapy to market for this progressive, burdensome disease.

I am proud of all of our progress in 2023 and the potential ahead for Mirum. We look forward to continuing to grow the impact of our programs, providing life-changing medicines to patients with rare disease.

Now before I turn the call over to Peter to discuss our commercial business, I wanted to welcome our new Chief Medical Officer, Dr. Joanne Quan, who joined Mirum in January. We are thrilled to have Joanne and her extensive leadership and scientific expertise helping to drive the value creation we see ahead for Mirum. We'll hear from her later on this call.

And for now, I'll turn the call over to Peter to discuss our commercial business. Peter?

Thanks, Chris. We are excited by the tremendous progress that we have made across our US and international businesses coming off of 2023, where we saw 138% growth in total net product sales compared to 2022. We are already seeing the benefits of our newly expanded pediatric hepatology franchise and enhanced offering amongst the patients and prescriber community.

I'm proud of the Mirum team's focus on patients while simultaneously driving the seamless integration of CHOLBAM and CHENODAL. And this is evident in the $69.6 million of total net product sales we achieved in the fourth quarter of 2023, which reflected growth across all three commercial medicines.

For LIVMARLI, total global net product sales grew to $41.4 million in the fourth quarter. Our US business saw $31.4 million and $111 million for the quarter and year, respectively, representing approximately 63% year-over-year growth. And internationally, we are seeing consistent strong uptake as well, but we continue to anticipate quarter-to-quarter variability in international revenue.

Moving on to CHENODAL and CHOLBAM, the fourth quarter was the first full quarter with these two medicines under Mirum's leadership. And I'm very happy with how quickly we have been able to transition these medicines into our business.

In the fourth quarter, we recognized net product sales of $28.1 million, the highest quarter to date for the bile acid products. And looking ahead, we expect steady growth for these two medicines in line with historical trends.

Taking all the strong dynamics in the business together, we expect net product sales to be $310 million to $320 million for 2024. This represents over 70% growth from 2023 with increased contribution from all commercially available medicines.

In summary, 2023 was a fantastic year for our team. As we expanded our portfolio to three commercial products, we grew our presence both in the US and worldwide. We continue to see the tremendous impact of all three products across their patient communities, and we look forward to further expansion in 2024 as we stay committed to our mission of delivering life-changing medicines to patients worldwide.

And with that, I'll turn it over to Joanne. Joanne?

Thanks, Peter. Before I begin, I'd like to say that I'm thrilled to join Mirum. This experienced team has accomplished so much in such a short period of time, and I'm excited to continue the momentum and progress in the treatment of rare diseases.

In 2024, we are looking forward to multiple regulatory and development milestones. From a regulatory perspective, we are tracking well towards our PFIC PDUFA date of March 13 and expect a decision for the EMA in the first half of the year.

Regarding CHENODAL and CTX, we're making good progress here as well. We've had positive interactions with the FDA, and no additional clinical studies are required to support our NDA submission, which is planned in the first half of 2024.

Turning to volixibat, we are also looking forward to our upcoming interim analyses in our VISTAS PSC study and our VANTAGE study in PBC patients. We are on track for the interim analysis to read out in the first half of this year. Note that the studies are now continuing to enroll patients, with the goal of supporting registration. As a reminder, the VISTAS PSC study will have a blinded interim analysis to support dose selection. Based upon the data, this will allow patients from the selected dose and placebo arms to be included in the pivotal data set.

For the larger indication of PBC, the study is designed so that we unblind and show the top-line results from the interim analysis, which will include data on pruritus improvement, change in serum bile acids, and safety. Both of these studies represent an important step towards addressing the accumulation of bile acids in broader patient groups with adult cholestasis, where a significant portion of patients are without adequate treatment options for their cholestasis and its severe symptomatic burden.

I am excited to be part of this team and look forward to sharing our progress with you this year. With that, I'll now turn the call over to Eric to discuss our financial results. Eric?

Thanks, Joanne. Earlier today, we issued a press release that included financial results for the quarter and full year, which I'll briefly summarize. Note, our 10-K filing is planned for next week as our auditors finalize the first 404(b) and other audit procedures for Mirum.

Total revenue in the fourth quarter 2023 was $69.6 million. And for the year ended December 31, total revenue was $186.4 million, including total net product sales of $178.9 million. This is compared to total revenues of $27.9 million and $77.1 million for the fourth quarter and full year 2022, respectively.

For operating expenses for the year ended December 31 were $293 million, which includes research and development expenses of $102.6 million, SG&A expenses of $145.9 million, and cost of sales of $44.5 million.

For the year ended December 31, 2023, net loss was $160.9 million, or $3.94 per share. Net loss for the year included noncash stock-based compensation expense of $35 million and intangible amortization of $10.4 million. This intangible amortization is largely reflected in our cost of goods sold. In the fourth quarter, COGS also reflected a reserve in excess of $5 million for inventory, primarily related to the bile acid acquisition.

For the year ended December 31, 2023, our cash used in operating activities was $70.9 million, down from $120.1 million the year before. We had cash, cash equivalents, and investments of $286.3 million as of December 31, 2023. We remain well-funded with a strong and self-sustaining business. Our increasing revenue base places us in an exceptional position to grow the business through clinical development and continued expansion of our global commercial presence over the coming years.

Now I'll turn the call back over to Chris for final comments.

Thanks, Eric. It has been a strong year for Mirum, finishing with the biggest-ever revenue quarter for LIVMARLI and the bile acid portfolio. We are poised for another great year in 2024 with three growing commercial products and with several clinical and regulatory catalysts as we strive to make continued advances for rare disease patients around the world. We look forward to keeping you updated on our exciting progress throughout the year.

And with that, operator, please open the call for questions.

(Operator Instructions) Jessica Fye, JPMorgan.

Hey, this is Nick on for Jess. Congrats on the quarter and thanks for taking our questions. Maybe looking at the 2024 net product sales guidance of $310 million to $320 million, can you maybe discuss a bit more about how much LIVMARLI growth is baked in there versus contributions from CHENODAL and CHOLBAM? And also, comment a little bit on LIVMARLI and Alagille, and maybe provide an update on what you're seeing on the competitive dynamics for Bylvay, if any?

Yeah, thanks for the question. And first, just from a starting point, we're not giving product level guidance at this point, but really great dynamics across the products. And I'll let Peter give a little color on what we're seeing across the business.

Yeah. And I think as you think about the component in some of the color commentary there, the bile acid product portfolio, we expect it to grow in line with historical trends, which have been kind of on the order of mid-single-digit year-on-year growth rates. And then looking into LIVMARLI growth case in the US, which has been strong over the last overall quarters of its marketing, expected to see it continue to move forward with that team. And then on the international side, we do expect quarter-to-quarter variability there for the LIVMARLI international sales.

And then your other question about competitive dynamics in Alagille, I think as you can see from the numbers here, it's really -- we haven't seen a measurable impact from those at all really. The LIVMARLI growth trajectory hasn't been impacted by that.

Great. And maybe just one more. Thinking about the VANTAGE study and how do Alagille patients go to first-line setting, second-line setting post-CDCA. Beyond the rate of pruritus observed across these two settings, can you maybe talk a little bit more about the differences in how it presents and/or maybe the severity of itch that is observed in these two patient populations?

Yeah. Joanne and I can speak to the difference between the line therapy.

Yeah. So as you know, pruritus is a big issue in both of these diseases. We have a broad patient population that we're accessing in terms of the volixibat studies. And actually, there's -- this is broader than, for instance, some of the other entrants in this space who are looking at biochemical abnormalities.

I'll remind you that we have agreement from FDA that provide us with the registrational endpoint, and both of these studies are actually positioned for registration after the interim analysis. So we feel pretty confident in terms of both the study design, the drug itself, our dose selection, and moving forward at this point.

Great, thanks.

Thanks for the questions.

Gavin Clark-Gartner, Evercore ISI.

Hi, this is Yesha on for Gavin. Just two questions for us. For the first one, for LIVMARLI, especially with the start of the year, just wondering if you have seen patients being reweighted for higher doses as they grow?

Happy to take the question. We have published some of that information last year. Not surprisingly, it is a weight-based product. And the growth that we've seen published probably with LIVMARLI, I think we have -- we did see weight-based dose adjustments.

Awesome. And then one more. For the EU business, do you have any commentary on potential implications of itch and refiling odevixibat in EU under a different brand name not with orphan status? And then I also want to confirm that there would be no reimbursement or access impact on LIVMARLI in the EU?

Thanks for your question. At this point, we're focused on getting access broadly across all international markets for LIVMARLI and Alagille and having great progress as we see demands continuing to grow across Europe and other international markets. Can't really speak too much to the Bylvay procedure other than that -- we're making great progress getting LIVMARLI really rolled out as standard of care in Alagille across all markets.

Great, thank you.

Thanks for the question.

Mani Foroohar, Leerink Partners.

Hi, good afternoon. This is Lili Nsongo on for Mani. I'm sorry I couldn't hear -- and apologies if it was asked earlier. I heard a question, but we couldn't hear the answer. This was regarding the growth expected for LIVMARLI in terms of weight-based increases as the patients get older. And to add to that, if you could comment in terms of how should we look -- or should we think about the weight and then the dosage for new patient versus existing ones?

Yeah. So the question -- just to make sure that I recap it here and ask for any color from Peter. Basically, the question there -- the original question was around, do we see adjustments to dose as patients that are on therapy over time per the label. And we do see that over time, I think where it's mentioned that there's been a recent poster presentation on it. So that is a dynamic that we see out with the treating physicians. And so were you able to -- did the microphone pick us up this time?

Yeah, we could hear you very clearly. Thank you. And as a follow-up, regarding the volixibat asset, could you maybe comment in terms of what the international growth opportunities are for those assets?

Yeah. So a question about CHENODAL/CHOLBAM growth opportunities. And I'll let Peter speak a little bit to the dynamic of what we have today and then also a little bit about the CHENODAL label expectations, expansion opportunity for CTX.

Yeah. I think with all products, we continue to see growth in line with historical trends, certainly with CHENODAL recently announced Phase 3 data for CTX and potential approval next year for CTX. I think there's an opportunity. CHENODAL has never been promoted for CTX before.

So I think there's an opportunity to find more patients through disease state awareness and hopefully increasing the diagnosis rate. One thing we know about CTX is maybe only about 10% of the patients are diagnosed and under management. So the opportunity there is to try to identify more patients and put them on therapy.

Thank you.

Thanks for the questions.

Mike Ulz, Morgan Stanley.

Hi, this is Rohit on for Mike. Thanks for taking our questions. Can you just talk about your expectations for the upcoming LIVMARLI PDUFA and PFIC, and any launch preface associated? And do you think that any patients are currently using it off-label? Thank you.

Yeah, thanks for the question, Rohit. On the regulatory front, we are where we expect to be, so excited about the PDUFA date coming up. And I'll let Peter speak a little bit to how we're preparing for that and some of the first opportunities we see there.

Yeah. We're really excited about the potential approval for LIVMARLI and PFIC. I think the March data reinforced the strong value proposition that LIVMARLI offers to our various stakeholder groups, and that will certainly help us. The physician prescribing universe is essentially identical to the Alagille audience, so there's really no need for meaningful operating expense increase to access it. And we do have a number of patients in the mid-20s who are receiving clinical rollover or expanded access -- LIVMARLI who would be eligible to roll over to commercial on approval.

Thank you.

Thanks for questions.

Steve Seedhouse, Raymond James.

Yes, hi. This is [Simurvani Kwan] on for Steve Seedhouse. So our first question is related to the gross margin. I think you mentioned there was an inventory charge related to the acquisition in 4Q. Just what are your expectations for gross margin in 2024 and perhaps also the OpEx trajectory in 2024?

For us, gross margin, we do expect that the intangible amortization will continue. I mean, it's largely related to the bile acid acquisition intangibles, which we're amortizing over 50 quarters. As far as traditional cost of goods, it consists of the actual cost of product and royalties so that will continue at approximately the same percentage of sales. And then we did have a larger than we expect going forward amortization -- or reserve for the inventory that came with the acquisition. So we might have some reserve in some quarters, but not to the extent we had in the fourth quarter.

In terms of overall operating expenses, R&D and SG&A, fourth quarter is probably pretty representative of what we expect the next few quarters.

Okay, thank you very much. And then just a question on your overall enrollment dynamics in VISTAS and VANTAGE. I think in VISTAS, your interim is only on 45 patients. So can you comment about the overall enrollment target dates? And do you see any differences between the studies in terms of the enrollment dynamics?

Thanks for the question. I mean, the simple answer here is we have patients in for the interim. We're continuing to enroll for part two now. And we'll be able to give better guidance for the full study enrollment at that interim when it comes up.

Okay. Appreciate it. Thank you very much.

Yeah, thank you.

David Lebowitz, Citi.

Hi, this is [Debanjana] on for David. Thanks for taking our call. We wanted to ask about the blinded PSC interim analysis. So beside the dose selection, would you share any other data points about blinded basis?

So we will be blinded in this interim and the phase design so that if it passes the threshold, it is designed to be predictive of a clinically meaningful and statistically significant positive pivotal analysis in the end. So that's all I can really share with you at this point, and it's really the special is developed based on what we know about the drug, this class of drugs, PSC in general and pruritus. So we feel pretty confident in terms of the design being robust and this being well set up to a [productive] registration study for us.

In terms of communication at the point of interim for the VISTA study, assuming a positive interim, we would communicate that the interim has occurred, and study continues as planned, which would be the extent of the information that we received here on the team as well.

Okay. So as a follow-up to that, could you tell us a bit more about -- I mean, while unlikely, is there any other scenario like that would see out of somehow like if you see that the efficacy is not crossing that threshold on a blinded basis that was [prespecified]?

So the study design in the event where that threshold is not met basically converts to an open interim analysis. We'd be able to look at the data, share top-line findings of it, and what the next steps are for the study in that scenario.

Okay. Thank you for the insight.

Yeah, thanks for the questions.

Brian Skorney, Baird.

Hi. On PBC, beyond pruritus, how are you thinking about the impact on outcomes and other markers in VANTAGE? And how can this help you make the case to physicians and patients?

Yeah, thanks for the question. I'll let Joanne speak a little bit to the registrational plan for PBC.

Yes. So in terms of the interim, we're just going to be looking at top line, so pruritis surveillance and safety as top line. And as you know, it is a big issue in this particular patient population for what's there's really no particular therapies. So we're pretty confident that this study, the way it's designed actually addresses an important unmet medical need at this point.

Yeah. And just to recap, one of the points made earlier, the eligibility criteria for the VANTAGE study does not have an alkaline phosphatase criteria. So it includes patients that are traditionally thought of as first line that has really only UDCA as on label and still experience the same rates and severity of pruritus as later lines of treatment. So a lot of unmet need across the PBC patient population.

Great, thanks.

Thanks for the question.

Ed Arce, H.C. Wainwright.

Hi, everyone. Thanks for taking my questions and congrats on another strong quarter. I have three, if I may. Firstly, on the VANTAGE study in PBC, as you said, it's a blinded data readout. Obviously, this is, as you mentioned, basically pruritus border versus placebo and whether it's stat sig. But I'm also wondering if there are specific thresholds of activity on pruritus that you're looking at, not just so much to proceed but also as you think about the competitive landscape, and where you'd like to see that come in.

Secondly, if you could speak a bit about the PFIC opportunity in terms of 2024, the sales, the speed of the sales ramp, what you're expecting the trajectory to be through the remaining quarters of this year.

And then lastly, I'm sorry, I didn't hear when Peter was reviewing -- I think it was Peter, the numbers for LIVMARLI both US and international as well as the bile acid products for the fourth quarter. Thanks so much.

Great, thanks for the question. Maybe I'll just hit on -- recap one of the points on VANTAGE, and then pass it over to Peter to talk about PFIC and recap some of those sales numbers.

The way we think about VANTAGE and volixibat in PBC, it really comes down to the highlight here on lines of therapy and where various agents are labeled and expected to be labeled. The majority of patients are first-line patients, and the majority of them have pruritus. So that's really the primary unmet need that we're going after. So showing a significant impact on that pruritus, we think, will be very clinically meaningful. And that's the lens that we're going to be taking towards that interim data when we look at it and make a decision on next steps and continuing to roll into the pivotal portion of the study.

With that, I'll pass it over to Peter on the next two points.

Yeah. Sorry, I'll try to speak up a little bit here. So on the PFIC 2024 revenue expectation piece, I think we'll be -- upon a potential approval here in March, we'll be spending a fair bit of time working closely with payers to get LIVMARLI positioned in their new-to-market policies. So I think if you think about 2024, we'd expect a lot of free drug or path with PFIC really coming in more in 2025. So somewhat similar to what we saw in the Alagille initial launch where the early quarters were high path drugs.

And then in terms of the numbers from Q4, LIVMARLI totaled $41.4 million worldwide, $31.4 million US, $10 million international, and then bile acid products were $28.1 million for Q4.

Great. And then maybe just a further clarification on PFIC. I appreciate the comments. Just wondering given that you mentioned earlier there's about 20-ish patients right now on expanded access, how soon would you expect those to be able to roll over onto commercial drug?

Yeah. What we saw in the Alagille launch is that occurred in a quarter or two generally is what we saw. And so, yeah, I think that's probably consistent with our expectation for those [25] or so.

Thanks so much.

Thanks for the questions.

Jonathan Wolleben, Citizens JMP.

Hi, it's Katherine on for John. I had two quick questions. One is I'm trying to follow up on volixibat and just how you guys see it fitting into the PBC paradigm in the setting of other approved agents that might potentially be effective. Also on pruritus, whether you see kind of the combo therapy, sort of a monotherapy for earlier patients?

And then also just as far as preparing for the PFIC launch, I know you said that there's not going to be too much of an investment as far as SGA growth. But like what else is kind of being done to get the word out there about PFIC or do most of these physicians already know that it's coming?

Thanks for the questions. And just to recap the PBC positioning one more time here, the VANTAGE study includes first-line patients that really are -- when you look at the eligibility criteria for the PPAR programs, for example, and how bezafibrates gets used outside the US, we are upstream of that setting where when a patient is biochemically controlled, they can still have substantial pruritus. So that's the area where IBAT can play a very unique role in being in front of the other second-line therapies, the PPARs and OCA, for example. So pretty unique positioning that we see for PBC.

I'd add on, in PSC, really exciting opportunity here where volixibat is positioned to be the first-and-only therapy for PSC by using pruritus as an endpoint, really gives an outcome to use for bringing a new therapy to these patients. So quite excited about the positioning there. And I'll pass it over to Peter for part two here.

Yeah. In regards to PFIC, obviously, there's been -- there's no promotion until an approval. But, I mean, I just kind of emphasize that it's a really small number of physicians that take care of these patients. In the US, I mean, you're probably talking about on the order of 100 physicians in the entire country that take care of PFIC patients. There have been presentations at the major medical conferences on the data, Phase 3 data, as well as the Phase 2 data going back for years. So I think there's a relatively high awareness of the data.

And certainly, from Alagille approval and commercialization, a lot of comfort with LIVMARLI's clinical profile, kind of familiarity with using it, prescribing it, working with our patient support hub, the Mirum Access Plus program, co-pay support, et cetera. So I think that's probably a fair summary of where things stand today.

Thanks so much.

Yeah. Thanks for the questions.

Thank you. There are no additional questions at this time. I will pass it back to Chris Peetz for any closing remarks.

Great. Thanks again for everyone for joining us today. Before ending the call, I do want to put a plug in for Rare Disease Day tomorrow. It's a day to build awareness for the more than 7,000 rare diseases impacting patients around the world and celebrate some of the meaningful advances in research that we've seen in recent years.

Tomorrow, as part of Rare Disease Day, we're excited to be able to share a manuscript published in Hepatology, featuring long-term data in patients with Alagille syndrome treated with LIVMARLI. So please join us in supporting the many advocacy groups that passionately lead efforts to support patients and research in rare disease tomorrow. And have a great evening. Good-bye.

That concludes today's conference call. Thank you. You may now disconnect your line.