Mirum Pharmaceuticals - Q2 2024

Transcript

Operator (participant)

Good afternoon, everyone, and welcome to the Mirum Pharmaceuticals Q2 2024 Financial Results and Business Update. My name is Carla, and I will be coordinating your call today. During the presentation, you will have the opportunity to ask questions by pressing Star followed by one on your telephone keypad. If you change your mind, please press Star followed by two. I will now hand you over to Andrew McKibben, Vice President of Investor Relations and Finance, to begin. Andrew, please go ahead.

Andrew McKibben (VP of Investor Relations and Finance)

Thanks, Carla, and good afternoon, everyone. I'd like to welcome you to Mirum Pharmaceuticals Q2 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 Q2 of 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?

Chris Peetz (CEO)

Thanks, Andrew, and good afternoon to everyone. I'm excited to share with you the outstanding progress we've made this quarter with our commercial medicines and pipeline. It's been a strong quarter across the board, with continued growth, important regulatory achievements, and positive volixibat interim results. On the commercial side, adoption of our medicines continues to grow, with total net product sales of $77.8 million across LIVMARLI, Chenodal, and Cholbam, representing a 139% increase from the Q2 of last year. Building on this strength, we've also achieved important regulatory milestones for our commercial medicines. We submitted our NDA for Chenodal and CTX, which, if approved, will allow us to take additional steps to reach this underdiagnosed population and provide an opportunity for orphan exclusivity.

For LIVMARLI, I'm very happy to say that we are now approved for cholestatic pruritus in PFIC in the U.S. and for the treatment of PFIC in Europe. We recently announced a U.S. label update to reduce that age to 12 months and older. We're looking forward to bringing LIVMARLI to PFIC patients, given the impressive clinical impact that we've seen in this population. I'm also excited to announce the initiation of another potentially label-enabling study for LIVMARLI in cholestatic pruritus. I'll let Joanne speak to some of the details, but in short, cholestatic pruritus is not limited to Alagille syndrome, PFIC, PSC, and PBC. We see multiple additional rare disease settings where patients develop cholestasis and experience significant pruritus.

Supported by high interest from physicians and compelling response case studies, we are launching the EXPAND study to bring LIVMARLI to patient communities that would otherwise be challenging to study individually. Collectively, across these settings, we estimate there are at least 500 patients in the U.S. alone that would be eligible for this indication. And finally, we took an important step towards advancing volixibat towards potentially pivotal data with the positive interim readouts of the VISTAS PSC and VANTAGE PBC studies. Our VISTAS PSC study exceeded the pre-specified efficacy threshold and is continuing enrollment to the full study readout. With no approved therapies in PSC, we are positioned to bring the first medicine to this patient community.

The interim results of the VANTAGE study in PBC were also very encouraging, with a statistically significant improvement in pruritus and a patient population that spans first and second-line PBC. I'm happy to say that enrollment is progressing well for both programs. It was a packed Q2 for Mirum. So to dive into the details, I'll turn the call over to Peter to start with our commercial business. Peter?

Peter Radovich (COO)

Thanks, Chris. I'm pleased to report another strong quarter across all three commercial products, and we continue to track well towards our full year revenue guidance of $310 million-$320 million. Starting with LIVMARLI, total global net product sales grew to $47.2 million this quarter, which represents a 45% increase compared to the same quarter last year. In the US, sales were $35.5 million, while international sales were $11.7 million. Growth continues to be driven by new Alagille syndrome patient additions, comprised of both prevalent patients and newly diagnosed, a dynamic we expect to persist going forward. We're also beginning to see prescriptions for PFIC patients, and our recent label expansion to include patients 12 months and older, provides incremental opportunity, given that PFIC is generally diagnosed when children are young.

Internationally, LIVMARLI demand growth was strong, and I'm pleased to say that we achieved a favorable outcome in our price negotiations with Germany. Stemming from this, we saw some price reference impact on international sales in Q2. We expect this to run its course in the next quarter or two. We were also very happy with the European Commission's recent endorsement of LIVMARLI for PFIC, three months and older, which highlights the significant benefit of LIVMARLI for these patients. Lastly, we saw nice demand growth from Cholbam and Chenodal in the Q2, where we recognized net product sales of $30.5 million. Overall, I'm thrilled with the continued strong commercial performance in the first half of the year and proud of the Mirum team's continued execution.

We are on a solid path to achieve our full year guidance of $310 million-$320 million and continued growth.

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

Joanne Quan (Chief Medical Officer)

Thanks, Peter. We had an exceptional quarter, highlighted by the impressive interim analyses for the VISTAS study in PSC and the VANTAGE study in PBC. I'll give a quick recap of the results. Starting with the VISTAS study in PSC, we set a pre-specified threshold for continuation based on both efficacy and safety. The blinded interim analysis met this threshold, and our independent data review committee recommended proceeding with the 20 milligram BID dose, and that the study continue without any changes. The blinded analysis confirms a meaningful treatment effect and also allows us to include these patients in the total patient number for the final analysis. We're happy with how the study is enrolling and anticipate completing enrollment in the second half of 2025. Moving on to the VANTAGE study in PBC, we're thrilled with the interim results.

Both doses of volixibat showed a substantial and statistically significant reduction in itch, an approximately 2.3-point improvement over placebo. Based on this, the VANTAGE study will also continue with the 20 mg BID dose, consistent with the VISTAS study. The results support volixibat's potential as an important advance for patients suffering from cholestatic pruritus. We also observed reductions in serum bile acids and improvements across multiple dimensions on the PBC-40, most notably fatigue. We look to complete enrollment in 2026 for this larger study. Overall, these results are significant for PBC patients, suggesting that volixibat has the potential to set a new standard in addressing the burden of cholestasis. We've already ramped up enrollment efforts and are targeting up to 100 total sites. Shifting gears a bit, I would like to talk about the new phase 3 EXPAND study.

Mirum has received a number of requests for compassionate use for LIVMARLI in patients with cholestatic pruritus across a variety of ultra-rare indications. We believe these conditions share a common pathogenic mechanism, cholestasis, leading to elevated serum bile acids, which results in persistent pruritus. Based on the good responses we've seen in some individuals receiving compassionate use, we are optimistic that LIVMARLI can play a significant role in the treatment of pruritus for these patients. EXPAND is a randomized, double-blind, placebo-controlled study evaluating LIVMARLI for treatment of pruritus over 20 weeks. EXPAND study will enroll patients with cholestatic pruritus associated with a range of conditions such as biliary atresia, secondary sclerosing cholangitis, and other less common conditions. Our target is to enroll approximately 45 patients, and we expect to complete enrollment in 2026. I look forward to providing further updates on VISTAS, VANTAGE, and EXPAND in the coming quarters.

I'll now turn it over to Eric to discuss our financial results. Eric?

Eric Bjerkholt (CFO)

Thanks, Joanne. Earlier today, we issued a press release that included financial results for the Q2, which I'll briefly summarize. Net product revenue in the Q2 2024 was $77.8 million, compared to net product revenues of $32.5 million in the Q2 last year. Total operating expense for the quarter ended June 30 were $102 million, which includes R&D expense of $32.7 million, SG&A expense of $49.2 million, and cost of sales of $20.2 million. The total operating expense for the quarter included approximately $17.7 million of non-cash charges, of which $5.7 million was included in cost of sales. For the quarter ended June 30, 2024, net loss was $24.6 million or $0.52 per share.

Our cash, cash equivalent, and investment was $295.4 million as of June 30, 2024, a reduction of $7.4 million from the end of the prior quarter. Cash used in the Q2 included the payment of a $10 million milestone to Takeda upon FDA approval of the LIVMARLI PFIC indication. With our robust commercial performance and continued financial discipline, we are in an excellent position to support the development of our pipeline and growth of our commercial business. Now, I'll turn the call back over to Chris for final comments.

Chris Peetz (CEO)

Thanks, Eric. It's been a great first half of the year. I'm proud of the Mirum team and our strong execution. We are well positioned to continue to advance our four strategic priorities: to grow our commercial business, expand the indications of our approved medicines, advance volixibat in adult cholestasis, and continue to look for opportunities to grow the pipeline. With that, operator, please open the call for questions.

Operator (participant)

We will now begin the question and answer session. If you would like to ask a question, please press star followed by one on your telephone keypad. If you change your mind, please press star followed by two. When preparing to ask your question, please ensure your devices are muted locally. Our first question comes from Dae Gon Ha from Stifel.

Dae Gon Ha (Analyst)

Hey, good afternoon, guys. Thanks for taking our questions, and congrats on the progress. Two from us, one commercial, and one clinical, I guess. Starting with commercial, as we look at the approval label across Alagille and PFIC in the U.S., it's kind of a palindrome between LIVMARLI and Bylvay. So I was hoping if you could maybe comment a little bit on what you've learned from perhaps Bylvay's experience in Alagille that you can implement to broaden LIVMARLI's reach within the PFIC segment before further label expansion can come down the pike. And then in terms of clinical side, Joanne, enrollment progressing favorably sounds great. Is there any initiative for you to perhaps accelerate enrollment into VISTAS and VANTAGE trials? Thanks so much.

Chris Peetz (CEO)

... Thanks, Dae Gon, for the question. You know, on the, you know, first kind of a comment on the, the labeling and label expansion we've seen for LIVMARLI. And can circle back for any follow-up questions, but what I think you're asking is just how the sequencing has gone for LIVMARLI, and it's played out really well. I think we're in a position of kind of very strong leadership in Europe, where we're the only product approved for both indications. In the US, we're now we see it as very equal footing, where we're now approved for both indications. Initial reception has been quite strong, and you know, the data for LIVMARLI in both indications, we think tells a really compelling story for prescribers, and that's what we're seeing play out in the real world.

So in terms of that kind of label sequencing, I think it's largely played out and to the favor of LIVMARLI. And then I'll let Joanne maybe comment on the enrollment strategies.

Joanne Quan (Chief Medical Officer)

Yeah. Yeah, thanks for the question. You know, like I said, we're happy with how the enrollment is going. You know, as you've noticed, we've been very excited by the interim analysis results on the PBC and the PSC, and we share that with our investigators, and they share the excitement on that and really are seeing the potential impact that this has as a medicine for both patient populations. You know, we're continuing to work with our existing sites and continuing the expansion as we previously talked about. So, you know, we're happy with where our enrollment is going.

Dae Gon Ha (Analyst)

Great. Thank you very much.

Chris Peetz (CEO)

Thanks for the questions.

Operator (participant)

The next question comes from Anif Roho from Leerink Partners.

Anif Roho (Analyst)

Hey, guys. Thanks for taking the question. A couple of quick ones. First, when we think about the novel expansion population in cholestatic pruritus, can you give us a sense of how you think about the duration of that study and the time horizon in which we might see results, recognizing it's a little bit of a heterogeneous population? And then we have a commercial quick follow-up.

Chris Peetz (CEO)

Yeah, sure. Thanks for the questions. And maybe Joanne, and then let Peter take the follow-up.

Joanne Quan (Chief Medical Officer)

Sure. So, you know, we are just launching the study now. And as we said, we plan to complete enrollment in 2026. It is a bit of a heterogeneous group of patients, but we expect that, you know, some patients will have biliary atresia as a cause, some secondary sclerosing cholangitis, and then a variety of other causes. This is really based on our experience in compassionate use. So, you know, we're actually pretty confident in terms of our understanding the role of IBAT inhibitors in treatment of cholestasis, and think that this extends its, this potential use to a wide variety of patients who, you know, for each of these, it would be difficult to study.

So we're excited to study them all in this EXPAND study and get some results and hopefully support some wider use.

Anif Roho (Analyst)

That's helpful. And then when you think about sort of more on the commercial side, obviously, there's a little bit of a some element of seasonality in this market, and so the pendulum swings one way early in the year and tends to swing the other, certainly around three Q, as we saw a couple of years ago. How should we think about the tempo of new patient adds and any sort of operational details we should think about in terms of seasonality across the next few quarters, looking forward?

Chris Peetz (CEO)

Yeah. Thanks for the question. I mean, one, you know, one thing to just kind of remind on, reflecting back to Q1, you know, we did see in the US with LIVMARLI and the bile acid products impact on our Q1 number from the Change Healthcare cyberattack. So that's one thing to keep in mind as you think about quarter-to-quarter trends here. And, you know, as far as seasonality goes, across three products, I can't say that we've identified, you know, you know, any real seasonality in these products. I mean, they're, you know, kind of ultra-rare to rare products with, you know, relatively low underlying volume, which can lead to kind of quarter-to-quarter variability, quite frankly. But whether that occurs in one quarter versus another, I can't say that there's a really strong effect there.

Okay. And on what time horizon should we expect sort of the, sort of OUS pricing reference dynamics to play out? Is that something we should think about sort of recurring and sort of eroding itself, playing out over the course of the next couple of quarters? Is that primarily a Q2, Q3 event? Like, how should we think about baking that into sort of how we model?

Yeah, exactly. We saw the effect in Q2, we expect it in Q3, and, you know, our expectation is by the time you're into Q4, that effect is gone and all of the kind of demand volume growth that we're seeing flows through to the top line.

Anif Roho (Analyst)

Perfect. Thanks, guys. I know you got a bunch of people in the queue. I'll hop off.

Chris Peetz (CEO)

Thanks for the questions.

Operator (participant)

Our next question comes from Gavin Clark-Gartner from Evercore ISI.

Speaker 13

Hi, guys. This is Yeshwanth for Gavin. Thanks for taking our question. We just have two. The first one, could you just touch on the level of confidence in that 45-patient sample size for EXPAND, and maybe how you powered the study, and then one follow-up after that?

Chris Peetz (CEO)

Yeah, Yeshwanth, thanks for the question. I think I'll, I'll let Joanne kind of comment a bit, but I think the one thing to kind of say to give some context here is that now, at this point, using IBAT in these cholestatic settings. I think we've, we've seen a pattern here that you can drive really dramatic response if you're at the right dose on bile acid and cholestasis. So the thinking behind this study design is based on having actually seen that same profile play out in a number of compassionate use patients. So good, really strong evidence from the individual case studies that in aggregate basically make this population. So feel good about launching the study. That's why we designed it, and that's what compelled us to put it together.

Maybe Joanne can speak a little bit about sample size.

Joanne Quan (Chief Medical Officer)

Yeah, thanks for the question. So, you know, the sample size was, you know, based on powering, based on the, our primary endpoint, which is an observer-rated visual. So this is a scale that we understand well, based on our previous experience, you know, from prior studies with, with LIVMARLI. So we feel pretty confident that this is an appropriate, sample size for us to see, a solid treatment effect.

Speaker 13

Awesome. Thank you. And then one follow-up. Was there any data from EMBARK that makes you confident enrolling BA patients in this trial?

Chris Peetz (CEO)

I'll pass that back to Joanne.

Joanne Quan (Chief Medical Officer)

Sure. Yeah, well, thanks for the question. You know, I think it's important to note that the patient population that we're enrolling in EXPAND is actually quite different than the one that we're, that we did enroll in EMBARK. With EXPAND, we're really, you know, taking patients, really at any point of their journey. And for biliary atresia, many of these patients will have had a Kasai a number of years ago, but over the course of time, their condition deteriorates, and they may develop with liver failure. So this is quite a different population than EMBARK, where we took really incident patients around the time that they had a Kasai. So this is quite a different patient population, and on top of that, we're including other causes of cholestatic colitis with chronic liver disease.

Chris Peetz (CEO)

Yeah. Yes, I'd also add on that in those compassionate use case studies, there have been biliary atresia patients, and they're, you know, quite a bit older than the EMBARK age, where they're enrolled as infants. And you do see that, a kind of hallmark response to IBAT treatment. So, I think we've now figured out how to dose these medicines and what settings to advance them in.

Speaker 13

Super helpful. Thank you so much.

Chris Peetz (CEO)

Yep. Thanks for the questions.

Operator (participant)

The next question comes from Jessica Fye from J.P. Morgan.

Jessica Fye (Analyst)

Hey, guys. Good afternoon. Thanks for taking my questions. I had a few. First, where should we look for presentation of the interim PBC data for volixibat, and what kind of additional details should we expect when you present those results? For example, are there subgroups where we should expect to learn more? Could we see itch results broken down by severity of diseases defined by ALP levels or additional data on liver biomarkers or more details on the improvements observed in the fatigue dimension of the PBC 40? And then separately, on the business development front, can you provide a bit of color about just what type of assets and which disease areas are most interesting to you? And lastly, can you just comment on your IP estate across LIVMARLI and volixibat in terms of what IP you currently have and any pending applications? Thank you.

Chris Peetz (CEO)

Thanks, Jess, for the questions. I can kind of. Maybe I'll take a shot at the first and the last, and pass it over to Peter to talk about our BD strategy. Yeah, first comment on the, you know, further data from the PBC study. We're preparing an abstract. We'll work on getting it submitted for an upcoming congress, and can't really predict, when and where that lands and what's in it. So, you know, just say that we're looking at a number of the elements that you talked about there, to consider for that, abstract. And then on, intellectual property, actually, I'll direct you to our, our corporate deck.

In the backup slides, we have a summary of that that's been recently added, and highlight the a 2040 family of granted and pending patents that really tie back to the quite unique dosing profile for IBAT in general and LIVMARLI and volixibat in particular. That's led to all of these great advances we've seen across the programs that we're talking about here. And there's more detail in this, in the backup of our public materials there, that you can reference. Maybe Peter can talk about BD strategy. Sure. Yeah, thanks for the question, Jess. We, you know, we're focused on rare disease. We really like rare pediatric opportunities. You know, essentially asking ourselves the question, programs where we could add a lot of value, underappreciated programs.

We have a really strong development, regulatory, commercial group in rare disease, so looking, you know, looking in that kind of a corridor. We have a high bar. We're very disciplined. We have a really strong base business with a great runway of catalysts in front of it. So we take, you know, we take a lot of scrutiny to these opportunities.

Jessica Fye (Analyst)

Thank you.

Chris Peetz (CEO)

Thanks for the questions.

Operator (participant)

The next question comes from Mike Ulz, from Morgan Stanley.

Speaker 13

Hi, this is Rohan for Mike. Thanks for taking our questions. Just in PFIC, do you expect to pursue a label expansion to patients below 12 months? And then can you just talk about how many patients are typically diagnosed that are below 12 months and what the opportunity there is? Thanks.

Chris Peetz (CEO)

Thanks, Rohan, for the question. You know, overall, we feel that our label now with this PFIC expansion down to 12 months, it's in a really strong place. Similar to what we do with Alagille, we're evaluating the potential to submit yet another sNDA based on the infant data that's now mature. But frankly, haven't come to a decision on that yet. So it's something that we could pursue, though feel that we're in a position now where we capture most of the LIVMARLI targeted patients for both Alagille syndrome and PFIC.

Speaker 15

Thank you.

Chris Peetz (CEO)

Thanks for the question.

Operator (participant)

The next question comes from David Lebowitz from Citi.

David Lebowitz (Analyst)

Thank you very much for taking my question. Now, with respect to the EXPAND trial, given the heterogeneous population, how do you think the FDA would view it from a label expansion perspective?

Chris Peetz (CEO)

Thanks for the question, David. I'll ask Joanne maybe to talk a little bit about some of the thinking that went into that, and discussion with FDA.

Joanne Quan (Chief Medical Officer)

Yeah. Thanks, David, for the question. You know, interesting that you asked the question that way, because, in fact, the study came about because the FDA actually had suggested it. You know, we were receiving compassionate use request, and so the FDA at one point said, "You know, why don't you put these into a study?" So, the EXPAND study has been designed, you know, keeping that input in mind. And so, you know, we do think the commonality is really cholestatic pruritus, you know, cholestasis, elevated serum bile acids, and we know the effect that it has, that ought to have on pruritus in that setting.

So, we're pretty confident in terms of, you know, our ability to execute the study and really in terms of the result that we'll see, once it gets executed.

David Lebowitz (Analyst)

Got it. Thanks for taking my question.

Chris Peetz (CEO)

Thanks for the question.

Operator (participant)

The next question is from Steven Seedhouse, from Raymond James Financial Inc.

Steven Seedhouse (Analyst)

Yeah, good afternoon, thanks for the questions. Just on Expand, how are you going to be measuring pruritus? 'Cause it seems like this trial would include pediatric and adult patients, depending on the condition. So I'm just curious how you're going to standardize measuring the endpoint across disease types.

Joanne Quan (Chief Medical Officer)

Yeah, thanks for the question. We have an observer-rated itch score, which has been validated and which we do have experience with in prior studies. And that's really designed for a pediatric population. So, you know, it's right of you to recognize that in a pediatric versus adult population, we can have different endpoints. But, you know, we feel pretty confident in terms of the design of the study and the selection of the endpoint, and the fact that we have experience with this endpoint and know how to use.

Chris Peetz (CEO)

Yeah, and just to kind of, you know, follow up on that, that pediatric data set, that's the primary cohort, 45 patients. That, you know, that's where the kind of primary analysis is. So the adults scores will be part of a supplemental cohort, and think of the analysis plan designed in that way. Primary is based on the pediatric score.

Steven Seedhouse (Analyst)

Ah, okay. And so the adults would be self-reported itch, or would there be a second observer?

Joanne Quan (Chief Medical Officer)

Yeah, so it would-

Steven Seedhouse (Analyst)

How does the endpoint measure look?

Joanne Quan (Chief Medical Officer)

Right. So, for the adults, it's a self-reported endpoint.

Steven Seedhouse (Analyst)

Okay.

Joanne Quan (Chief Medical Officer)

That's one reason for us having them in a separate cohort. Based on our discussions with clinicians, you know, and just our experience with compassionate use, we do believe the majority of the patients will be pediatric. But we do think there will be some adult patients, and so we're studying them in a supplemental cohort, and we'll analyze those, too.

Steven Seedhouse (Analyst)

Okay, and then the formulation here, is this just gonna be the same liquid formulation that's commercially available? Or-

Chris Peetz (CEO)

That's right. Yep.

Steven Seedhouse (Analyst)

Okay. And then just, last question, and thanks for the multipart question. Are biliary atresia patients that enrolled in EXPAND that were maybe pruritic, either on enrollment, and that's... Or excuse me, that enrolled in EMBARK, eligible to enroll in EXPAND? Or is anyone who's been treated compassionately eligible to enroll in this study, or are you excluding anyone with prior exposure to LIVMARLI?

Chris Peetz (CEO)

Well, first, just on the, you know, to reiterate on the differences in the setting, the Embark population was so young. They were too young even really to recognize pruritus for the most part. You don't see that show up until basically what would've been the very end or even after the time period that Embark was looking at. So it is a very distinct setting to go after these, you know, what are gonna be, think of as, getting towards grade school-aged children, for a lot of instances.

Steven Seedhouse (Analyst)

So just to follow up on that, Chris, if there are patients that responded by bile acids or bilirubin or some metric in EMBARK, are they eligible to enroll in EXPAND if they're a biliary atresia patient?

Chris Peetz (CEO)

I mean, the comment I'd make there-

Steven Seedhouse (Analyst)

Yeah.

Chris Peetz (CEO)

The EMBARK study results recall there that, you know, we really, in that setting, you're not seeing a response signal, right? So those patients are either had successful Kasai procedures, you wouldn't expect them to progress again for several years, or they had a transplant already. So it's kind of, we didn't even see it as a really relevant question. We can circle back on... I don't know the exclusion criteria off the top of my head right now, but-

Joanne Quan (Chief Medical Officer)

Yeah

Chris Peetz (CEO)

... it was, it's just such a different patient population. You wouldn't see those necessarily connect.

Steven Seedhouse (Analyst)

Okay, makes sense. Thanks so much.

Chris Peetz (CEO)

Yep.

Operator (participant)

The next question comes from Brian Skorney, from Baird.

Speaker 12

Hi, this is Charlie on for Brian. Just a couple questions on the bile acid portfolio. Previously, it was sitting around, you know, low to mid-20 per quarter. So just wondering... You know, you said it's demand growth, but what you're seeing, if you could give a little more detail there, as well as if you're planning for any other opportunities to expand, the value you're getting out of Cholbam. Thank you.

Chris Peetz (CEO)

Yeah, thanks for the question. I'll ask Peter to give some color.

Peter Radovich (COO)

Yeah, you know, and I think I'd kinda go back to, with the bile acid products that, you know, if you're looking at Q1 versus Q2, just a reminder that Q1 was artificially low because of the cyberattack that occurred that impacted, you know, pharmacy claim processing in the US. So that's just one dynamic to keep in mind. And we, you know, we do expect kind of steady demand growth, kind of in line with historical averages and what you've seen over time with, you know, reminding you that there is quarter-to-quarter variability with these products. And in terms of Cholbam expansion, yeah, that we think the Cholbam label is a, is in a great, great spot.

It, you know, facilitates the use and reimbursement of that product across the various settings where it's been established. So, you know, no, no, no, you know, no major plans right now to focus on expansion there.

Chris Peetz (CEO)

Thanks for the question, Charlie.

Operator (participant)

The next question comes from Jon Wolleben from Citizens JMP.

Jon Wolleben (Analyst)

Hey, thanks for taking the questions. A couple on PFIC for me. Wondering, you know, without talking about sales here, you know, any, you know, metrics on the PFIC launch in the US, things are going well, things that you guys could improve upon, throughout the rest of the year? And then with the label expansion recently, can you discuss the added risk of the propylene glycol toxicity? Any observation of that in the clinical trials, or is this just a risk that FDA wanted to include?

Chris Peetz (CEO)

Yeah, I'll kind of break that up between Peter and Joanne to talk about the commercial and safety aspects.

Andrew McKibben (VP of Investor Relations and Finance)

Yeah, yeah. Thanks for the question. Certainly real happy with how we've come out of the gate with PFIC. Have seen... We had, you know, a number of patients, you know, transition from our clinical trial expanded access programs to commercial product. That's proceeded very well, as well as de novo prescriptions for PFIC patients come in. You know, we've talked about it before, that we expect, you know, revenue contribution from PFIC in 2024 to be, you know, pretty, pretty modest given reimbursement. We expect a fair bit of free drug shipment this year for PFIC. It is contemplated, you know, a little bit in our, in our guidance, but, you know, really expect 2025 to be, where PFIC starts contributing more. So, you know, good, good start.

And then with regards to the propylene glycol and the clinical development program, I'll let Joanne speak to that.

Joanne Quan (Chief Medical Officer)

Yeah. Thanks for the question. Just to be clear, we have not seen PG toxicity in our clinical studies. And in the context of the PFIC label expansion, we and the FDA looked pretty carefully and kind of combed through all of that patient experience data. You know, this concern from the FDA really arose in light of the younger patients being considered for the expansion. And, you know, we have seen warnings about PG toxicity with other labels, for instance, so this is not unique to us. You know, we do feel comfortable that the physicians who are prescribing this know their patients, they know what to look for, they're appropriately monitoring.

So we think from a practical perspective, that this is well handled in terms of the routine patient care.

Jon Wolleben (Analyst)

Got it. Thanks.

Chris Peetz (CEO)

Thanks for the question.

Operator (participant)

The next question is from Ed Arce, from H.C. Wainwright.

Speaker 14

Hi, everyone. This is Thomas Yip asking a couple questions for Ed. Thank you so much for taking our questions. Perhaps first, just wondering for Chenodal, how will you characterize the additional commercial opportunity in CTX as an on-label indication? I suppose in terms of quantity and also how relative to our Chenodal existing sales?

Chris Peetz (CEO)

Yeah. Thanks, Thomas, for the question. I'll ask Peter to comment on that, give some color on, again, the undiagnosed population for CTX.

Andrew McKibben (VP of Investor Relations and Finance)

Yeah, and you know, we as we look at the CTX opportunity, the, you know, best estimates from literature, market research, KOLs, probably somewhere between 1,000-2,000 prevalent patients with CTX in the United States, but only 10% of those are diagnosed right now, is the best estimate of what we see. So, you know, probably the biggest opportunity is if we can increase that 10% to something higher. So we are, you know, investing in disease state awareness, you know, initiatives, reaching out to physicians who may see these patients as they're presenting with various symptoms on their journey to a diagnosis. And trying to both increase the rate of diagnosis as well as speed up the time to get to the diagnosis.

And have seen a lot of interest from, you know, prescribers, you know, neurologists and other physicians kind of take interest in that. And then, you know, if Chenodal is approved by FDA and we're able to promote, you know, certainly the product has never been promoted before. So I think there'll be an opportunity out there, and even for the diagnosis patients in clinic, you know, raise awareness of the benefits of... potential benefits of Chenodal, support reimbursement, things like that.

Speaker 14

Mm-hmm. Understood. Thanks. And maybe one more from us. This one for volixibat. Regarding Vantage, Vantage in this case, has the FDA or the EMA reviewed the interim data that you have so far? Any feedback from any regulatory agency?

Chris Peetz (CEO)

Thanks, Thomas, for the question. You know, the in the cadence here of regulatory review, we have had a pre-IND discussion designing the studies, and the next opportunity would be after we have final results is what our plans are. So no kind of interim discussions on plans.

Speaker 14

Okay. Thank you. Thank you so much for taking my questions.

Chris Peetz (CEO)

Yeah, thanks for the questions.

Operator (participant)

That was our last question, so I will hand back over to Chris Peetz, the CEO, for any final remarks.

Chris Peetz (CEO)

Thank you, operator, and thank you all for joining us today. We appreciate the support for Mirum and our programs, and have a good evening. Bye.

Operator (participant)

This concludes today's call. Thank you for joining. You may now disconnect from the call.