Mirum Pharmaceuticals, Inc. Q4 FY2023 Earnings Call

Good afternoon, everyone. Thank you for being here for Mirum Pharmaceuticals' Q4 and Year End 2023 Financial Results and Business Update. My name is Tia and I will be moderating today's call. During the presentation, all lines will be muted, but we will have a question-and-answer session at the end. Now, I will hand the call over to Andrew McKibben, Vice President of Investor Relations and Finance. Please go ahead.

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 the subsequent reports filed with the SEC. With that said, I'd like to turn the call over to 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 the 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 III study to patients with a potential label expansion. We're also preparing for the submission of the positive RESTORE Phase III results of CHENODAL and CTX in the first half of the year, an important label-enabling opportunity. And we also made great progress with the VISTAS and VANTAGE studies for volixibat in PSC and PBC. Patients for the interim analysis 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'm 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 diseases. 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 from 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.

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 among 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 and 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.

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 13th 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're also looking forward to our upcoming interim analysis in our VISTAS PSC study and our VANTAGE study in PBC patients. We are on track for the interim analysis to readout 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'm 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.

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 31st, 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 31st 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 31st 2023, net loss was $160.9 million or $3.94 per share. Net loss for the year included non-cash 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 31st 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 31st 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 set 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.

We would now begin the Q&A session. The first question comes from the line of Jessica Fye with JPMorgan. Please proceed.

Hey. This is Nick on for Jess. Congrats on the quarter. And thanks for taking our question. 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 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 kind of 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 on 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 has just 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, we haven't seen a measurable impact from those at all 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?

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

Pruritus is a significant concern in both diseases. We have a wide patient population involved in the volixibat studies, and our approach is broader compared to some competitors focusing on biochemical abnormalities. We have received FDA agreement that outlines our registrational endpoint, and both studies are positioned for registration following the interim analysis. We are confident in the study design, the drug, our dose selection, and our progress at this stage.

Great. Thanks.

Thanks for the questions.

The next question comes from the line of Gavin Clark-Gartner with Evercore ISI. Please proceed.

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?

I'm happy to answer your question. We shared some of that information last year. It's expected that it is a weight-based product. Regarding LIVMARLI, we have indeed observed weight-based dose adjustments reflecting the growth we've seen.

All right. 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?

Yes. Good 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 demand 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.

Thank you. The next question comes from the line of Mani Foroohar with Leerink Partners. Please proceed.

Hi. Good afternoon. This is Lili Nsongo on behalf of Mani. I apologize for not being able to hear the previous discussion, especially the answer to the question I caught. This relates to the growth anticipated for LIVMARLI in terms of weight-based increases as patients age. Additionally, could you elaborate on how we should consider weight and dosage for new patients compared to existing ones?

Yes, the question was about whether we see adjustments to dosage as patients continue therapy over time. We do observe that happening. There was a recent poster presentation discussing this. It's a dynamic we see with the treating physicians. Was the microphone working this time?

Yeah. 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 and 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 III data for CTS and potential approval next year for CTS. I think there's an opportunity. CHENODAL has never been promoted for CTS before. So I think there's an opportunity to find more patients through disease awareness and hopefully increasing the diagnosis rate. One thing we know about CTS 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 your questions.

The next question comes from the line of Mike Ulz with Morgan Stanley. Please proceed.

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.

Thanks for the question Rohit. On the regulatory front 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.

Yes. 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 I think that will certainly help us. The physician prescribing universe is essentially identical to the Alagille audience so there's really no need for a 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 to LIVMARLI, who would be eligible to rollover to commercial on approval.

Thank you.

Next question.

The next question comes from the line of Steve Seedhouse with Raymond James. Please proceed.

Yes, hi. This is someone on for Steve Seedhouse. Our first question is about the gross margin. I believe you mentioned there was an inventory charge related to the acquisition in the fourth quarter. What are your expectations for gross margin in 2024 and possibly the operating expense 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 sort of traditional cost of goods, it consists of the actual cost of product and royalties. So that will continue at approximately the same sort of 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. 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.

Yes, thank you.

The next question comes from the line of David Lebowitz with Citi. Please proceed.

Hi. Thanks for taking our call. We wanted to ask about the blinded PSC interim analysis. Besides the dose selection, would you share any other data points on a 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 clinical pivotal 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 kind of 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. As a follow-up to that, could you tell us a bit more about any other possible scenarios that might occur if the efficacy does not meet the specified threshold on a blinded basis?

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

Okay. Thank you for the insights.

Yes, thanks for the questions.

Thank you. The next question comes from the line of Brian Skorney with Baird. Please proceed.

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?

Yes. Thanks for the question. I'll let Joanne speak a little bit to kind of the registrational plan for PBC.

Yes. In terms of the interim, we will focus on the top line, specifically pruritus and safety. As you know, pruritus is a significant issue for this patient population, and there are currently no specific therapies available. We are quite confident that the design of this study addresses an important unmet medical need at this time.

Yes. 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.

Thank you. The next question comes from the line of Ed Arce with H.C. Wainwright. Please proceed.

Hi everyone. Thanks for taking my questions and congratulations on another strong quarter. I have three questions, if I may. Firstly, regarding the VANTAGE study in PBC. As you've mentioned, it's a blinded data readout focusing on pruritus versus placebo and its statistical significance. I'm curious if you are considering specific thresholds of pruritus activity, not just to advance, but also in the context of the competitive landscape and where you'd like to see those levels. Secondly, could you elaborate on the PFIC opportunity for 2024, specifically your sales expectations and the pace of sales growth for the remaining quarters of this year? Lastly, I apologize, but I missed the information when Peter was reviewing the numbers for LIVMARLI, both in the U.S. and internationally, as well as the bile acid products for the fourth quarter. Thank you.

Thank you for the question. I want to recap one of the points regarding VANTAGE and then hand it over to Peter to discuss PFIC and review some of the sales figures. Our focus with VANTAGE and volixibat in PBC centers on therapy lines and the expected labeling of various agents. Most patients are first-line, and a significant number experience pruritus, which represents our primary unmet need. We believe demonstrating a notable impact on this pruritus will be clinically significant. We'll consider this perspective when analyzing the interim data to decide on the next steps and continue progressing to the pivotal phase of the study. Now, I'll turn it over to Peter for the next discussion points.

I apologize, I'll try to speak more clearly. Regarding our revenue expectations for PFIC in 2024, if we receive approval in March, we plan to work closely with payers to integrate LIVMARLI into their new market policies. For 2024, we anticipate a significant amount of free drug support with PFIC, with more substantial contributions expected in 2025. This is somewhat similar to what we experienced during the initial launch of Alagille, where early quarters had a high path for the drug. In terms of our Q4 numbers, LIVMARLI generated $41.4 million globally, with $31.4 million from the U.S. and $10 million internationally. Additionally, bile acid products accounted for $28.1 million in 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?

Yes. What we saw in the Alagille launch is that occurred in a quarter or two generally is what we saw. And so, yes, I think that's probably consistent with our expectation for those 2025 or so.

Thank you very much. Thank you. The next question comes from the line of Jonathan Wolleben with Citizens JMP. Please proceed.

This is Catherine on for Jon. I had two kind of quick questions. One is a follow-up on volixibat and just kind of, 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 SG&A growth, like what else is being done to sort of get the word out there about PFIC there’s mostly patients already know that it's coming.

Thanks for the questions. And just to kind of recap the PBC positioning one more time here. The VANTAGE study includes first-line patients, and when you look at the eligibility criteria for the PPAR programs for example and how decide 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, PPARs and OCA for example. So, quite excited about the positioning there. I'm going to pass it over to Peter for part two here.

Yes. Regarding PFIC, there hasn't been any promotion until an approval is granted. It’s important to note that only a very small number of physicians are involved in the care of these patients. In the US, there are likely around 100 physicians across the entire country who treat PFIC patients. Major medical conferences have presented data from both Phase III and Phase II studies over the years, so there is relatively high awareness of this data. With the approval and commercialization of Alagille, there is significant confidence in LIVMARLI's clinical profile, along with familiarity in prescribing it and using our patient support services like the Mirum Access Plus program and co-pay support. This is a fair summary of the current situation.

Thanks so much.

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 for today. Before ending the call, I do want to put a plug-in for Rare Disease Day tomorrow, today 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 in research and rare disease tomorrow and have a great evening. Goodbye.

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