Mirum Pharmaceuticals Inc

NASDAQ:MIRM

Earnings Call Analysis

Mirum Pharmaceuticals Sees Strong Growth and Expands Pipeline in Q3 2024.

In the third quarter of 2024, Mirum Pharmaceuticals reported remarkable growth, with net product sales increasing by 89% year-over-year to $90.3 million. This rise is attributed to strong demand for all three commercial medicines, particularly LIVMARLI, which saw a significant uptick in both U.S. and international markets. The company has raised its 2024 revenue guidance to between $330 million and $335 million. Additionally, Mirum received breakthrough designation for Volixibat in treating cholestatic pruritus, further emphasizing its strong pipeline. Recent regulatory progress includes a priority review for Chenodiol's indication in CTX, with a PDUFA date set for December 28, 2024.

An Outstanding Quarter for Mirum Pharmaceuticals

Mirum Pharmaceuticals is celebrating another successful quarter, with net product sales reported at $90.3 million, reflecting an impressive 89% increase from the same period last year. This growth underscores the successful commercial execution of their three key medicines, notably LIVMARLI, which has seen strong international uptake, especially in treating cholestatic pruritus conditions.

Increased Revenue Guidance for 2024

Due to the robust performance of their commercial medicines, Mirum has raised its full-year revenue guidance for 2024 to a range of $330 million to $335 million, indicating continued optimism about their market positions and sales trends, especially for LIVMARLI and Chenodiol.

Breakthrough Designation for Volixibat

The company received breakthrough therapy designation from the FDA for Volixibat, aimed at treating cholestatic pruritus in patients with primary biliary cholangitis (PBC). This designation is based on positive interim results from their VANTAGE study, highlighting the continued unmet need in PBC treatments. This approval enhances Mirum's pipeline opportunities and illustrates their commitment to addressing rare disease needs.

Continued Pipeline Progress and New Developments

In addition to Volixibat's success, Mirum has advanced its clinical studies in both PBC and primary sclerosing cholangitis (PSC), maintaining on-track enrollment guidance. Excitingly, the planned Phase 3 EXPAND studies evaluating LIVMARLI in additional cholestatic pruritus settings have commenced, expanding potential label indications. Furthermore, Mirum plans to initiate a Phase II study for MRM-3379, targeting Fragile X syndrome, a significant addition to their neurology-focused pipeline.

Growing Commercial Impact and Market Expansion

Mirum's commercial team reported strong sales growth for LIVMARLI, particularly in the U.S., where sales reached $43.5 million. The demand is expected to grow further following recent pricing and reimbursement advancements, particularly for PFIC in Europe. The potential market for Chenodiol-CTX is estimated at 1,000 to 2,000 prevalent patients in the U.S., with only 10% currently diagnosed, presenting a significant opportunity for Mirum to increase awareness and, consequently, their sales.

Financial Discipline Amid Growth

Despite reporting a net loss of $15 million or $0.32 per share for the quarter, Mirum continues to showcase financial discipline and independence. Positive operating cash flow was achieved for the first time this quarter, highlighting the company’s progress in achieving sustainable financial performance while advancing their product development pipeline. As of September 30, their cash and investments totaled approximately $293.8 million.

Strategic Future and Continued Commitment to Rare Diseases

Looking ahead, Mirum remains focused on leveraging its strengths in rare disease management to explore new high-impact therapeutic initiatives. The recent in-licensing of MRM-3379 demonstrates their commitment to diversifying their portfolio and addressing under-served areas within genetic neurology. The management team is confident about future prospects as they continue to expand their market presence and further develop innovative treatments.

Earnings Call Transcript 2024-Q3

[Operator]

Hello, everyone, and welcome to the Mirum Pharmaceuticals Third Quarter 2024 Financial Results and Business Update. My name is Seb, and I'll be the operator for your call today. [Operator Instructions].



I will now hand you over to Andrew McKibben, Vice President of Investor Relations and Finance. Please go ahead.

[Andrew McKibben, executive]

Thanks, Seb, and good morning, everyone. I'd like to welcome you to Mirum Pharmaceuticals Third Quarter 2024 Conference Call. I'm joined today by our CEO, Chris Peetz; our President and Chief Operating Officer, Peter Radovich; 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 third quarter 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-Q and subsequent SEC filings for more information.



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

[Christopher Peetz, executive]

Thanks, Andrew, and good morning, everyone. It has been another outstanding quarter for Mirum with strong commercial execution and advancing pipeline, we have made excellent progress across our 2024 strategic objectives, accelerating our growth as a leader in rare disease.



As a reminder, our goals this year have been to drive continued growth across our 3 commercial medicines, expand the labels for both LIVMARLI and PFIC in Chenodiol and CTX leverage the strength of IBAT inhibition in the adult settings of PSC and PBC and continue expanding our portfolio of medicines for rare diseases. We have delivered on all of these this year. Specifically, in the third quarter, all 3 commercial medicines saw continued growth with net product sales of $90.3 million, an 89% increase from the third quarter of 2023.



This very strong quarter was driven by the continued underlying trends across the brands with increased PFIC and international uptake for LIVMARLI. With this strong execution from our commercial team, we are increasing our 2024 guidance to $330 million to $335 million in full year net product revenue.



We have also made excellent progress with our pipeline. Volixibat has been granted breakthrough designation for cholestatic pruritus in PBC based on the VANTAGE study interim results. As a reminder to qualify for this designation, the FDA requires preliminary clinical evidence that indicates that the drug may demonstrate substantial improvement over existing therapy on at least one clinically significant endpoint. This designation emphasizes the continued unmet need in PBC and the strong early treatment effects seen in the interim results, which have now been accepted as a late-breaking abstract at the upcoming American Association for the Study of Liver Diseases meeting.



Our clinical studies in PBC and PSC remain on track with our enrollment guidance and the Phase 3 EXPAND studies evaluating LIVMARLI in additional settings of cholestatic pruritus is now underway. For Chenodiol, I'm pleased to announce we received priority review for our NDA in CTX with the PDUFA date of December 28. And finally, I'm also happy to share that we've expanded our early development pipeline with the addition of MRM-3379, a candidate for the treatment of patients with Fragile X syndrome.



Fragile X syndrome is a rare genetic disorder that is a leading cause of intellectual disability that affects approximately 50,000 male patients across the U.S. and Europe with no approved therapies. Strategically, this program aligns well with the capabilities we are building in rare genetic neurology to support Chenodiol and CTX. We will continue to look for opportunities to leverage our industry-leading rare disease expertise in patient settings where there's a clear need for high-impact medicines. I'm proud of all of our progress to date in 2024 and the potential ahead for Mirum.



I'll now turn the call over to Peter to go over the commercial business. Peter?

[Peter Radovich, executive]

Thanks, Chris. I'm pleased to say that we had another strong quarter with total net product sales of $90.3 million. For LIVMARLI, total global net product sales grew to $59.1 million in the third quarter. U.S. sales were $43.5 million, while international sales were $15.6 million. In the U.S., we continue to see solid growth in Alagille syndrome and are seeing added contribution from PFIC as reimbursement has come through earlier than we expected.



Internationally, we continue to see strong underlying demand growth in Alagille syndrome from both our core markets and our distributor partners despite pricing headwinds. With LIVMARLI now approved in PFIC in Europe, pricing and reimbursement negotiations are underway. We also saw continued steady growth from CHOLBAM and Chenodiol, which had $31.2 million of net product sales in the third quarter, and the commercial team is looking forward to our PDUFA date for CTX in December.



Overall, it's been a tremendous year for the commercial business. We continue to grow our impact for Alagille syndrome patients. We expanded the label for LIVMARLI, allowing us to extend our reach to the PFIC community. We effectively navigated price negotiations in Europe, and we successfully integrated the bile acid portfolio, leading to record sales. With the increased full year guidance of $330 million to $335 million, we look forward to ending the year on a high note and continuing our strong execution into 2025.



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

[Joanne M. Quan, executive]

Thanks, Peter. It was a productive quarter for our pipeline, and I'm excited to share our progress. First, I want to highlight the progress we're making with Volixibat. We're thrilled with the breakthrough therapy designation for Volixibat as a potential treatment for cholestatic pruritus in patients with PBC. This designation highlights the significant burden patients face and the need for an effective treatment.



The decision was based on the positive interim analysis of the Phase 2B VANTAGE study, which showed statistically significant improvement versus placebo in pruritus for PBC patients treated with Volixibat. I'm happy to share that we will be presenting this data as a late breaker at AASLD, the Liver Meeting next week. For both the PSC and PBC programs, we've had great engagement with investigators and advocacy groups over the last few months. We're happy with how both studies are progressing and remain on track to have full enrollment by the second half of 2025 for PSC and in 2026 for PBC.



Moving on to EXPAND. As a reminder, the study represents an exciting potential label expansion opportunity for LIVMARLI in additional settings of cholestatic pruritus. We have started opening sites and are excited to start screening patients. Looking toward the end of the year, we're on track for our December 28 PDUFA date for Chenodiol-CTX. This is an exciting step forward in extending our presence in rare genetic neurology.



Next, I'm thrilled by the opportunity in Fragile X syndrome with MRM-3379. Fragile X syndrome, or FXS, is the most common monogenic cause of intellectual disability and is also characterized by anxiety and language delays. It is an X-linked disorder and males tend to be more severely affected. MRM-3379 is a selective phosphodiesterase or PDE4D inhibitor, and this mechanism has shown proof of concept in Fragile X in the clinic. We believe MRM-3379's brain penetrant profile is differentiating, and we plan to evaluate its potential in males with FXS in a Phase II study.



We plan to start this study next year. I'm pleased with the progress we made this quarter across our different assets and look forward to providing updates in the future.



I'll now turn it over to Eric. Eric?

[Eric Bjerkholt, executive]

Thanks, Joanne. Earlier today, we issued a press release that included financial results for the third quarter, which I'll briefly summarize. Overall, we continued our trend of strengthening quarter-over-quarter financial performance. I'm excited to announce that in Q3, we achieved positive operating cash flow for the first time.



Net product revenue in the third quarter 2024 was $90.3 million compared to net product revenues of $47.7 million in the third quarter last year. Total operating expenses for the quarter ended September 30 were $103.9 million, which includes R&D expense of $31.7 million, SG&A expense of $50.5 million and cost of sales of $20.8 million.



The total operating expense for the quarter included approximately $18 million of noncash stock-based compensation and depreciation and amortization expense, of which approximately $6 million was included in cost of sales. For the quarter ended September 30, net loss was $15 million or $0.32 a share. Our cash, cash equivalents and investments was $293.8 million as of September 30, a reduction of $1.6 million from the previous quarter.



The third quarter cash used included the payment of a $10 million milestone to Takeda upon European approval of the LIVMARLI PFIC indication. The upfront fee for MRM-3379 was $7.5 million, which we will pay in the fourth quarter with cash on hand. Under the deal terms, we are subject to a $7.5 million Phase III start milestone and certain regulatory and sales-based milestones.



In summary, we continue to grow the commercial business and advance and enhance our drug development pipeline, all while remaining financially independent and fiscally disciplined.



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

[Christopher Peetz, executive]

Thanks, Eric. It has been a great quarter for Mirum. Our commercial programs are performing well with strong growth resulting from increased full year guidance. Our pipeline is delivering with volixibat's recent breakthrough designation and the initiation of the EXPAND study for LIVMARLI and added MRM-3379 with a planned Phase II start next year. And the Mirum team has driven all of this with financial discipline, setting us up for a strong finish to the year.



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

[Operator]

[Operator Instructions] First question is from Gavin Clark-Gartner from Evercore ISI.

[Gavin Clark-Gartner, analyst]

Congrats on all the progress. So I just wanted to focus in on Fragile X. So first question here, maybe just for those who are less familiar, what's the current registrational endpoint in Fragile X? Is it on behavioral or cognitive clinical endpoints? And is there any opportunity to pursue an accelerated path?

[Christopher Peetz, executive]

Gavin, thanks for the question. I'll actually turn it over to Joanne to talk about our strategy and thinking on endpoints.

[Joanne M. Quan, executive]

Yes. Gavin, thanks for the question. Our thinking is that we can use the NIH toolbox as a registrational endpoint. Obviously, we've just acquired the program, so we haven't had further discussions with the FDA, but we do think this is a very viable path forward. We recognize that in the past, different endpoints have been used, and I think that's also been problematic for the field. And if you look at the history, there really have been no positive studies other than for [indiscernible], which is also a PD4 inhibitor.



However, with our molecule, we think that there's the selectivity and really the high brain penetration actually provides some advantages in developing forward. So we're really excited in terms of moving this forward and do think that there's a viable path forward with the FDA.

[Christopher Peetz, executive]

And just to add one comment on the NIH toolbox endpoint. This is the patient conducted test and similar to all of the programs that we have here at Mirum, leaning on the patient-reported outcomes and our experience with that on what -- is part of what gets us excited about this program and the clinical plan.

[Gavin Clark-Gartner, analyst]

Got it. That's helpful. And are you planning to have any engagement with regulators prior to initiating the Phase II? Or will next engagement likely be end of Phase II meeting?

[Joanne M. Quan, executive]

Yes. Thanks, Gavin, for the follow-up. We will be engaging with the FDA early next year on this program.

[Operator]

Our next question is from Jessica Fye at JPMorgan.

[Jessica Fye, analyst]

I had a couple -- first, on volixibat, can you share a little more detail on the data we should expect from the late-breaking presentation at AASLD from the VANTAGE interim? How much of an update will this be? What would you focus the street on? And what subgroups, if any, will you present? That's one.



Second, LIVMARLI, it looks like growth was really solid quarter-over-quarter, year-over-year. I think last year, 3Q, you talked about seasonal headwinds. Did you see any of that this year?



And then lastly, on business development in the context of this latest in-licensing, how do you see the company evolving with this asset kind of going beyond the kind of rare liver disease kind of legacy focus? And do you expect to kind of remain active on the BD front on the back of this in-licensing?

[Christopher Peetz, executive]

Thanks, Jess, for the question. I'll touch on the quick comment on volixibat and BD strategy and let Peter speak to the commercial trends. On for the volixibat late breaker, we're just a handful of days away from these being released. So just kind of point you towards that and the update is coming soon with data there. Real focus, the top line is already out there, right, that we've seen just really strong response on pruritus. That is the registrational endpoint we're pursuing. So still very excited about this data and excited to share the update.



On BD strategy, I think just to take a step back and put the 3379 addition to the -- as an early-stage program, we do see this as one of several steps that we've been pursuing now for years here at Mirum with a team that's been focused on rare disease, in particular, rare genetic disease and programs that are overlooked that can add a lot of value.



So the 3379 program is a great example of that, where it fits well with our capabilities in terms of how genetic diseases get diagnosed and treated on the development side, a thoughtful approach to endpoints and patient-reported outcomes. And really as the last comment I'll make is I see this as kind of a bookend of example of things that we look at between the transaction last year, bringing on commercial products. You see this as kind of the earlier end of the spectrum in terms of where we focus our time for BD strategy.



And with that, maybe I'll pass it over to Peter on the commercial side.

[Peter Radovich, executive]

Yes. With regards to the LIVMARLI trends, Jess, as you mentioned, in 2023, we did comment on a bit of a slowdown in some of the summer months with LIVMARLI. It really has not been something we observed at all in 2024. This quarter was really solid continued growth in Alagille syndrome in line with kind of what we've been seeing with Alagille syndrome and a strong kind of launch performance from PFIC in the U.S. as well as strong growth in international.

[Operator]

Our next question is from Mani Foroohar from Leerink Partners.

[Unknown Analyst]

You have Brian on for Mani. Congrats on the quarter. I guess a few on 3379. Can you just provide any specifics around the deal terms such as royalties or future milestones that we should expect for this program? And then more specifically on the OpEx line, do you expect this program to impact OpEx moving forward? Or is it pretty negligible?



And then just one on the commercial front. Can you share any color on where you're seeing this acceleration in PFIC is coming from? So whether that be new patient starts or switches from a competitor and what that means for growth moving forward?

[Christopher Peetz, executive]

Great. Brent, thanks for the question. I'll pass it off to Eric and Peter to touch on both questions.

[Eric Bjerkholt, executive]

Yes. Thanks. So I did provide some comments on the financial terms in my commentary that we just went through. So the upfront was $7.5 million and really the only sort of pre-regulatory approval milestone is the $7.5 million Phase III stock milestone. Our royalties, we're not going to comment on, but they're very typical for a deal of this stage. So pretty modest.



In terms of the increase in spend, it's too early to be too specific because we're early in terms of developing our plans for this asset, both on the clinical side as well as the manufacturing side. But to give you just a rough sense in terms of percentage of our R&D spend, you could think about it being sort of in the mid-teens percentage-wise.

[Christopher Peetz, executive]

Yes. And just to kind of put that in perspective of how we looked at bringing this program into Mirum, see it as very much an efficient early-stage program that is quite targeted investment to get to proof of concept. So the Phase II design and investment into that from the deal terms to the clinical spend, really not a big step in terms of the amount of dollars spent.

[Peter Radovich, executive]

And yes, Brian, to your question on what's driving the PFIC performance. I think an overarching comment is really reimbursement. Our market access and reimbursement team did a great job securing coverage for PFIC kind of sooner than we would anticipate based on even our Alagille approval as well as other rare disease approvals when you usually expect a few more quarters of new-to-market policies where reimbursement might be slower to come online. So that came online faster than we thought.



In terms of sources of demand, we've talked in the past about our expanded access clinical trial rollover patients being in about the low 20s in the U.S. that were ready to be rolled over after launch. And then we are seeing de novo demand. Probably the majority of those are IBAT naive, and we are seeing some switches as well.

[Operator]

Our next question is from Dae Gon Ha from Stifel.

[Dae Gon Ha, analyst]

Congrats on the quarter, looking pretty bright ahead. I guess a couple of questions from me as well. Just thinking about the OpEx growth or I guess, not OpEx, but the revenue guidance increase. Just curious if it is primarily driven by Alagille growth ahead in Q4? Or is it really going to be about PFIC as we think about modeling purposes?



When we think about EXPAND, Joanne, can you expand a little bit more? You said sites are opening. But in terms of outlook on cadence of patient enrollment and any kind of time line that you envision in terms of enrollment completion, that would be great.



And then lastly, on the MRM-3379. Just curious about your overall strategy on the neurology side. I mean, Fragile X is the starting point here. But are you thinking about expanding on the PDE4 inhibition for other indications? Is there anything that's lower-hanging fruit after Fragile X?

[Christopher Peetz, executive]

Thanks for the question. Maybe, Joanne, you want to start with the EXPAND question from there?

[Joanne M. Quan, executive]

Yes. Thanks for the question. In terms of EXPAND, we're right on track in terms of where we are, in terms of the study start. So we have sites up and running, and we expect to start screening shortly. Our guidance in terms of enrollment time line has not changed from before. So we expect to roughly 18 months or so and then [indiscernible] from there. So that's really right on track.

[Dae Gon Ha, analyst]

And then on the sales trends?

[Peter Radovich, executive]

Yes, Dan. So yes, we obviously raised our guidance to $330 million, $335 million in terms of what drives that. We continue to see strong Alagille growth in the U.S. kind of in line with historical trends. And yes, the uptick that we saw in Q3 and that is kind of coming forward in our guidance in Q4 is really driven by the PFIC launch in the U.S.

[Christopher Peetz, executive]

And just to kind of touch on the broader opportunity for PDE4D. There may be potential in other indications, but we're approaching this first in a very focused way to get to proof of concept in Fragile X in the Phase II program before we consider kind of putting broader dollars against it. So really looking forward to generating that first proof-of-concept data and what that can mean for Fragile X patients, and we'll go from there.

[Operator]

The next question is from Brian Skorney at Baird.

[Brian Skorney, analyst]

On the PDE4D, I know Shionogi is run a Phase III with Xanthomas in Fragile X. And so I'm just kind of wondering, is the Phase II data with that sort of the basis of the licensing deal here? And then can you maybe compare and contrast your molecule with the Shionogi one? And would you anticipate initiating Phase II before the readout of that study next year? Or would you maybe wait on those results to decide on potential endpoints and powering?

[Christopher Peetz, executive]

Yes. Thanks for the question, Brian. That did weigh into how we looked at the program. The Phase II proof-of-concept data from that program, I think, are quite interesting. I'll let Joanne speak to a little bit of the differentiation we see. But first, in terms of study start timing, see these as somewhat independent, though we are obviously monitoring that program [indiscernible]. But given the differentiated profile, I think that we could see stronger results than what comes out of that program.



I'll let Joanne speak to some of what we liked about this to bring it into the pipeline.

[Joanne M. Quan, executive]

Yes. Brian, thanks for the question. The molecule we have is highly selective. And I think one of the key differentiation points from the other molecule is just the high brain to plasma ratio simply because what we're trying to do is alter the cyclic cGMP levels within the brain. And so we think that our molecule has some potential advantages here. So I think that's a key differentiation point. And obviously, we'll keep that in mind as we look at results for the [indiscernible] program. We're excited about the potential for MRM-3379 and other potential applications [indiscernible].

[Operator]

The next question is from David Lebowitz from Citi.

[David Lebowitz, analyst]

Can you compare the decisions to in-license the Travere assets with 3379 and what you are thinking in general about your strategy relative to business development going forward?

[Christopher Peetz, executive]

Thanks, David. I can give a little bit of color, and I'll turn it over to Peter to talk about some of the things that we're active looking -- the spaces we're active looking at and kind of how the search came to both of these products. But the way I put some perspective on these 2 transactions and frankly, actually the founding transaction of Mirum and acquiring LIVMARLI and volixibat is really looking for overlooked value that the Mirum team can grow and expand on.



And the spectrum of types of transactions we've looked at from commercial to Phase I/Phase II ready is where I think our team has really deep expertise in rare disease, in particular, in rare disease settings that are genetically driven, where you can use patient-reported outcomes, have a lot of experience with that. And so on the commercial side, gives us the ability to drive financial performance, and on the clinical side, gives us the ability to build future growth into the company. So see those quite different transactions working together really well to build out the profile of Mirum.



I'll turn it over to Peter to talk about kind of what we look at.

[Peter Radovich, executive]

Yes. I mean I think you can -- it's a great question. You can look at these 2 transactions. The transaction with Travere for the bile acid products came by way of us being in the pediatric liver space, knowing what may be underappreciated and create significant value for health care professionals, patients, caregivers, and that led to our insight there, and we're happy with the performance that we've had in over a year of having these products in our hands, continuing to grow these to record highs.



And I think one point about Chenodiol, interestingly, is most of the prescribers are neurologists. And so really, for over the last year, we've kind of been in this neuro field, even though it's a bile acid replacement product, the manifestations are neurologic, and that's kind of gotten us into this field and the medical conferences, et cetera, where we kind of sort of gained insight and what may be another underappreciated program in 3379. So I think one theme is just high impact for patients and underappreciated rare disease programs.

[Operator]

The next question comes from Steve Seedhouse at Raymond James Financial.

[Timur Ivannikov, analyst]

This is Timur Ivannikov on for Steve Seedhouse. Congrats on the quarter. We have a couple of questions about Fragile X. So first one is, do you have plans to enroll patients younger than 18 years old? And at what point could you enroll those patients? And then in terms of the molecule specifics, do you know how much more CM activity you can achieve in the brain? That is how much is the xanthomas leaving on the table versus normal?

[Christopher Peetz, executive]

Yes. I'll start and let Joanne finish on some of the details, but I appreciate the question here. We are planning to interact with FDA early next year to finalize some of the Phase 2 elements, but do have some initial thinking on what we're going to propose. Caveat that with -- we'll update it with regulatory input.

[Joanne M. Quan, executive]

Yes. Thanks for the question. In terms of the age range, it's typical in these kinds of programs to start with adult patients and then try to step down in age. And that's the basic approach that we will have as well. Currently, we have information from the prior Phase 1 program, which included a fairly large number of adult healthy volunteers and elderly patients. And so we'll use that strategy and then step down in age. And that we think going down in age will be particularly helpful for Fragile X because most patients with Fragile X are diagnosed around age 3. So having something for children will be particularly impactful for this disease.



In terms of how much more central nervous kind of system activity, that's a pretty difficult thing to gauge. We do know that our brain-to-plasma ratio is actually quite a bit higher than the xanthomas. So we think that, that will give us some big advantages here. Obviously, the proof will be in the pudding in terms of looking at results, but we're pretty confident that this is an important differentiating feature for 3379 compared to any of the other compounds that are in the clinic.

[Operator]

The next question is from Mike Ulz at Morgan Stanley.

[Michael Ulz, analyst]

Maybe just one on chenodiol and CTX now that you sort of have a PDUFA date late December. Maybe just remind us what the potential market opportunity is there and what impact getting that in the label might have on sales?

[Peter Radovich, executive]

Thanks for the question, Mike. Yes. So we're really, really excited about the potential approval and the opportunity to be out there with active promotion. Just a reminder, while chenodiol is approved under a different indication and available under emergency use here for CTX, this will be a chance to have it on label and with active promotion.



We think the best literature estimates suggest there's about 1,000 to 2,000 prevalent patients in the U.S. with maybe only about 10% of those diagnosed. So a lot of our effort on disease state awareness and then ultimately, upon approval promotion will be try to increase that diagnosis rate. And to the extent we can increase it even a little bit, I think it could have a meaningful impact on the current sales trajectory you see reflected in our numbers today.

[Operator]

The next question comes from John Wolleben from JMP.

[Unknown Analyst]

This is Catherine on for John. I just have a quick question about kind of what you're seeing ex-U.S. and just global expansion for LIVMARLI, if you could comment on that. And then any updates to your views on the PFIC launch, given how strong the quarter has been?

[Christopher Peetz, executive]

Thanks for the questions, Catherine. Yes, the one comment I'd make on PFIC overall, this is early days and seeing good initial demand. But some of this was really just pull forward of reimbursement. So that's -- we do see this step-up as really being a stronger quarter than others because of that earlier reimbursement. But I'll let Peter speak to some of the international aspects.

[Peter Radovich, executive]

Yes. Yes, absolutely. I mean we've now have pricing and reimbursement approval in Alagille in the four major EU markets plus several midsized markets. So really proud of the execution our team has delivered there and distributor partners around the world continue to find more Alagille syndrome patients that we could potentially benefit with LIVMARLI. So the Alagille launch in Europe and international markets continues to go well. And yes, the PFIC approval came recently. So that is obviously not reflected in international sales now, maybe as you move into the back half of next year, mid to back half of next year with pricing and reimbursement coming on.

[Operator]

The next question comes from Ed Arce from H.C. Wainwright.

[Wing Yip, analyst]

This is Thomas Yip asking a couple of questions for Ed. So first question, perhaps following on the previous question. Can you give us more details on payer discussions for PFIC in the U.S. and EU? I suppose specifically, what percentage of target prescribers have you reached so far?

[Peter Radovich, executive]

Yes. I mean the beauty of PFIC really in every market we're active in is the prescribers are the same as Alagille syndrome and maybe even a subset of those, quite frankly. So I think we've -- at this point, in the U.S. launch of PFIC reached substantially all of them and have seen nice interest in the profile and great demand and sales as you're seeing in the Q3 numbers.



Early days in Europe, I think as we certainly about reaching Germany and places where we can launch more quickly, but I think we'll be reaching the vast majority of our PFIC providers as we move into next year and as the individual countries, pricing and reimbursement comes closer to where PFIC conversations are.

[Wing Yip, analyst]

And then perhaps another question for LIVMARLI. Just wondering if you can discuss enrollment progress for the EXPAND study or perhaps any initial investigator feedback that you have so far?

[Christopher Peetz, executive]

Thanks, Thomas, for the question. I mean I can just touch on that briefly in that sites are just now being opened. So we have sites open and starting to screen patients. So too early to comment on the initial progress there. But I will remind you that the whole idea for the study and the study design really came from prescriber interest and investigator interest and looking to get compassionate use access for patients that are -- that kind of fit within the protocol of the study. So this is an indication that's driven by physician and patient demand to add it to the LIVMARLI label. So still see a lot of that same dynamic that led us to put the study together in the first place.

[Wing Yip, analyst]

Understood. Perhaps one more question from us. So with in-licensing of the 3379, does that mean lucatinib disorder is now a target for Mirum or just rare genetic diseases in general?

[Christopher Peetz, executive]

Yes. Thanks for the question there. I mean, overall, it doesn't change what we're looking for. And we see rare disease itself as somewhat of a therapeutic area because of the commonality and how patients are diagnosed in these genetic conditions, the thoughtful approach that you need on endpoints, that all plays across all of these different settings.



And on the commercial team side, have commercialized and are active with a number of different therapeutic areas and prescribers. So while we see there's opportunities to build in some of these subspecialties we do see opportunity outside of them as well because we've shown that we can add value across a number of different settings, both clinically and commercially.

[Operator]

This concludes the Q&A session. I'll now hand the call back to Chris Peetz, CEO, to conclude the call.

[Christopher Peetz, executive]

Great. Thanks, everyone, for joining us today, and have a great day. Goodbye.

[Operator]

Thank you all for joining today's Mirum Pharmaceuticals Third Quarter 2024 Results Call. You may now disconnect.