Mirum Pharmaceuticals, Inc. (MIRM) Earnings Call Transcript & Summary

[Audio Gap] of ultra-rare cholestatic liver diseases. Approximately 1/2 of enrolled patients have biliary atresia, and patients were randomized to receive maralixibat or placebo during a 20-week placebo-controlled treatment period. Now let me walk you through the results in more detail. Starting with the primary endpoint. EXPAND demonstrated a statistically significant and clinically meaningful improvement in pruritus with maralixibat. Pruritus was assessed using a caregiver reported scale ranging from 0 to 4 corresponding to no itch and very severe itch, respectively. Across weeks 13 through 20, patients treated with maralixibat experienced a mean reduction in pruritus of 1.81 points from baseline. Putting the magnitude of this reduction in context of the 2.65 mean baseline value makes it particularly impressive. This reduction with maralixibat compares to 0.83 points for placebo, representing a placebo-adjusted treatment difference of 0.98 points and a p-value of 0.0004. The secondary endpoints further reinforce the primary efficacy findings and the biologic rationale underlying maralixibat mechanism of action. Serum bile acids were reduced by 70% with maralixibat compared with 3.5% with placebo, corresponding to a treatment difference of 69% and a p-value of less than 0.0001. Taken together, these findings demonstrate meaningful improvement in a symptom that matters greatly to patients and their caregivers supported by substantial reductions in the bile acid need to drive cholestatic pruritus. I want to spend a little more time on biliary atresia, where there are currently no approved treatment options. This was the largest patient stock group in EXPAND and the results closely mirrored the positive results observed in the overall study population. In the prespecified biliary subgroup, maralixibat achieved a mean reduction in pruritus from baseline of 2.15 points compared with 1 point for placebo, corresponding to a placebo-adjusted treatment difference at 1.15 points and a p-value of 0.0002. Importantly, the treatment effects deserved in patients with biliary atresia were highly consistent with the -- with other cholestatic liver diseases enrolled in EXPAND. Across both groups, we observed meaningful improvements in pruritus accompanied by substantial reductions in some bile acids. Now turning to safety. Maralixibat demonstrated a safety profile in EXPAND that was consistent with our prior clinical experience and no new safety signals were identified. Treatment emergent adverse events were reported in 96% of patients in both the maralixibat and placebo groups. Serious treatment emergent adverse events occurred in 20% of maralixibat treated patients and 18.5% of placebo-treated patients. There was one discontinuation from the study on the maralixibat arm and none in the placebo arm. Consistent with the mechanism of IBAT inhibition and our prior clinical experience with maralixibat, the most reported adverse events were diarrhea and abdominal pain, occurring in 64% and 20% of maralixibat treated patients, respectively. Importantly, no patient discontinued treatment due to diarrhea. Overall, we're very encouraged by these results. EXPAND met its primary endpoint and all prespecified secondary, while maralixibat demonstrated a safety profile consistent with our prior clinical experience. More broadly, EXPAND as to a growing and remarkably consistent body of evidence supporting IBAT inhibition as a therapeutic approach for cholestatic pruritus. Across 5 positive clinical studies in multiple cholestatic liver diseases, we continue to see meaningful reductions in pruritus accompanied by improvements in bile acid biology. Taken together, these findings reinforce our belief that targeting bile acid biology can deliver clinically meaningful benefit to patients suffering from post pruritus, regardless of the underlying disease. Now I'll turn it back to Chris.

Thanks, And we're very pleased with these results and excited about the potential to bring maralixibat to these additional settings. From here, our focus turns to the planned supplemental NDA submission in the first half of next year. This label expansion opportunity comes on top of the continued growth we're seeing in LIVMARLI in patients with allogesyndrm and PFIC. In today's update adds to an already remarkable year for LIVMARLI pipeline. The AtebrIos launch an FOP is on track to kick off this month, and we're excited about early feedback on the approval. This is an exciting growth opportunity for Mirum's rare genetic disease business. . And brilogatide's recent positive AZURE-1 readout gives us confidence in the upcoming AZURE-4 study readout later this quarter. Those two studies will be the basis of the planned BLA in the first half of next year. And volixibat provides further opportunity for the rare liver business. Avista's results earlier this year in PSC were granted breakthrough designation. We're moving forward with our strategy to interact with FDA ahead of an NDA submission planned in the first half of next year. Further, the VANTAGE study in PBC is on track for top line data next quarter. We're closing out the year with a lot of momentum and very excited about what lies ahead for Mirum. And with that, operator, please open the call for questions.

[Operator Instructions] Your first question comes from the line of Yigal Nochomovitz with Citigroup. We will take another question instead from Ryan Deschner with Raymond James.

Congrats on the readout today. On the roughly 70% reduction in serum bile acids, specifically regarding the biliary atresia patients, how clinically meaningful do you interpret this result to be? And I have a follow-up.

Thanks for the question. I would interpret that roughly 70% reduction as being very clinically meaningful. We have observed across multiple cholestatic liver diseases now that this degree of reduction is associated with improvements in pruritus that are also clinically meaningful. And we've observed the same thing here in the overall population and in the biliary atresia patients as well.

Appreciate it. And where do you expect pricing on a per patient basis to shake out relative to LIVMARLI and Alagi and PFIC. And could this be another situation where revenue could grow over time, specifically driven by the actual growth of the patients.

Thanks for the color, Ryan. First comment is no change in the pricing strategy for LIVMARLI, but pass it over to Peter to talk about launch expectations.

Yes, Ryan. The price for LIVMARLI has already established. So the unit pricing is kind of set, therefore, the kind of indication pricing is a function of dose and consumption. So this would be about a 50% more dose than the indication, which is about $400 to $500 net annualized per year. So that would be the kind of expand dosing for the protocol. And yes, you would expect to see weight-based dosing and dose changes over time with weight gain.

Your next question comes from the line of Josh Schimmer with Cantor Fitzgerald. We will take a question instead from Kalpit Patel with Wolfe Research.

Many congrats on clearing the study. Couple from us, one for the label. What's the minimum maximum ages that you're planning to seek a label for? And then second, have you looked at the percentage of pediatric patients who achieved a sustained 1 point or greater reduction from baseline over weeks 13 to 20? And if you have done that analysis, can you break that out for the BA and non-BA patients?

Thanks for the question, Kalpit. First on label, I expect from an age perspective, this to be pretty similar to what we see for Allegan PFIC, where there's a lower ends defined in basically infancy, a young childhood with no expectation on an upper end is how we expect this to be the case here. And just as a reminder, the inclusion criteria is our best indicator of how that indication statement plays out, which is effectively a definition of exclusion. So cholestatic pruritus, excluding some of the larger indications. And then I would pass it over to Rob, maybe to talk about what we've seen on some of the response rates on Edge.

Thanks, Chris. We saw a remarkably consistent results in terms of itch response. But in answer to your specific question, in the biliary atresia subgroup, roughly 90% of patients had at least a 1-point improvement in pruritus. And in the for all population, this was about an 8% response rate. So quite clinically meaningful improvement with maralixibat treatment.

Your next question comes from the line of Jessica Fye with JPMorgan.

This is Adam on for Jess. Just could you elaborate what are the remaining steps between now and the sNDA submission, please?

Thanks for the question. Pretty typical post readout where we'll be filing this data, putting it into a write-up with all the follow-up analyses to a supplemental NDA filing, really straightforward overall in getting to that in the first half of next year. Thanks for the question.

Your next question comes from the line of Brian Skorney with Baird.

Congrats on the data. I wanted to get your thoughts on the non-biliary atresia opportunity here. You enrolled about 50% of the study in non-BA and I think BA should be a pretty well population. Was there any stratification in the study to think about? Or do you think that there would be sort of 50-50 in terms of patient flow in the commercial setting of addressable BA patients and non-BA patients? And -- do you have any thoughts on sort of the penetration of diagnosis of the non-BA orphan cholestatic patients? Do you think it could be greater than the 2,000 BA patients when all is said and done once more diagnosis is pushed?

Yes. Thanks for the question, Brian. I mean it's a really good question. I mean the way I would think about it here, I mean, this study had 24 sites from U.S. and around the world. And roll it for a little over a year. And as you note, about half the patients were biliary atresia, half the patients were other. These were pediatric investigators. So I think that's important to know. It's kind of representative of kind of the practice dynamics and setting there. So in terms of how large that other bucket could be the non-biliary atresia bucket could be, I think that the actual study enrollment here is probably the best guide. As far as diagnosis, yes, biliary atresia is very well diagnosed, substantially all patients are diagnosed with infants. The basket of other, I think it's pretty variable depending on the indication. But certainly, we'd be hopeful that as you see often in new product introductions, as awareness of a new product but grows and there's something to do about pruritus and high bile acids, then hopefully, recognition and diagnosis would increase in those settings.

Your next question comes from the line of Joseph Thome with TD Cowen.

Congrats on the data. Maybe just we have the data out there, and you did mention the updated PFIC patient metrics on the last quarterly call. How are you seeing the breakdown any contribution between Alloga PFIC and the sort of other cholestatic disease bucket in your $1 billion plus LIVMARLI expectation from a revenue perspective? And then second, if you could just talk about your expectations for how quickly this could come to market? Would this be prior review situations there? Or kind of what's the base expectation given your interactions with the FDA?

Thanks for the question, Joe. Yes. On the latter part of it first, we would see this as a candidate for priority review, just given the unmet need in the setting. And I'll pass it over to Peter to talk about the breakdown of the $1 billion-plus piece.

Yes, I think the first message overall is this readout really gives us confidence in the plus part of that $1 billion-plus peak guidance that we have here, you see a lot of different ways to get there from these components the update we're providing in the materials today. If you look just at the biliary atresia component of the EXPAND study, it's about 1,000 addressable patients in the U.S., 2,000 U.S. plus Europe, that's comparable to Algea. Actually, when you think about the addressable population of -- maybe the two differences from algae dose here is different. It's about 50% higher. So that does play through the price. And then, of course, no competition in biliary atresia, although we've had pretty limited effects of competition in syndrome. So I think as you think about peak sales, the biliary treating opportunity would be the least as large as the Thanks for the question

Your next question comes from the line of James Condulis with Stifel.