Mirum Pharmaceuticals, Inc. Common Stock Study update

Please go ahead. Thank you, Kelsey, and good morning, everyone.

I'd like to welcome you to Mirum's conference call to discuss top-line results from the Phase III EXPAND study of LIVMARLI, or maralixibat, in ultra-rare settings of cholestatic pruritus. For prepared remarks, I'm joined today by our Chief Executive Officer, Chris Peetz, and our Chief Medical Officer, Rob Myers. Also joining us for the Q&A portion of the call are Peter Radovich, our President and Chief Operating Officer, and Eric Bjerkholt, our Chief Financial Officer. Earlier today, Mirum issued a press release announcing these results. A copy of that release and our SEC filing, along with a presentation summarizing the data, are available on 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 and financial guidance. These statements represent our judgment and knowledge 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 about these risks and uncertainties. With that, I'd like to turn the call over to Chris and Rob for some brief remarks before we open the call for Q&A.

Chris? Thanks, Andrew, and welcome everyone for another great update from the Mirum pipeline.

Today marks another important milestone in our effort to bring LIVMARLI to more patients living with ultra-rare cholestatic liver diseases. We are excited to announce that the Phase III EXPAND study demonstrated a statistically significant and clinically meaningful improvement in pruritus. In addition to meeting the primary endpoint, the study met all secondary endpoints, including showing a highly significant reduction in pruritus in biliary atresia patients. Results in biliary atresia are notable, as there are no approved medicines in this setting, and we estimate about 2,000 biliary atresia patients across the U.S. and Europe suffer from pruritus. Our next step is a planned supplemental NDA submission in the first half of next year. Stepping back, EXPAND is a great example of how we think about building Mirum.

We start with patient need, pair it with scientific potential, and then apply efficient execution to bring meaningful medicines to those patients. That approach has now translated into our fourth positive study readout this year, and we see continued opportunity for the Mirum business model ahead. Today, fewer than 5% of rare diseases have an approved treatment. We believe focused companies like Mirum can play an important role in changing that. Finally, before I turn it over to Rob, I'd like to thank the patients, investigators, and study teams around the world who made EXPAND possible.

Rob? Thanks, Chris. My first few weeks at Mirum have been exciting, and I'm thrilled to be here.

From the outset, the rationale behind EXPAND was straightforward. Many patients suffer from cholestatic pruritus due to rare liver diseases that are simply too uncommon to support traditional disease-specific development programs. As a result, many of these patients have historically had little or no opportunity to participate in registrational clinical trials. EXPAND was designed in alignment with and at the request of the FDA to address this challenge. Rather than studying a single disease, the trial enrolled patients with different rare cholestatic liver diseases that share a common underlying biology and a symptom that can profoundly impact quality of life, cholestatic pruritus driven by impaired bile flow. This innovative approach allowed us to generate meaningful data in patient populations that might otherwise never be studied individually. Importantly, the results strongly support that strategy.

The primary efficacy population in EXPAND included 46 pediatric patients with moderate to severe pruritus across a range of ultra-rare cholestatic liver diseases. Approximately one-half of enrolled patients had 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 zero to four, 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's 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 acids believed 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 subgroup in EXPAND, and the results closely mirrored the positive results observed in the overall study population. In the pre-specified biliary atresia 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 of 1.15 points and a P value of 0.0002. Importantly, the treatment effects observed in patients with biliary atresia were highly consistent with those with other cholestatic liver diseases enrolled in EXPAND. Across both groups, we observed meaningful improvements in pruritus accompanied by substantial reductions in serum 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 1 discontinuation from the study in the maralixibat arm and none in the placebo arm. Consistent with the mechanism of IBAT inhibition in 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 pre-specified secondary endpoints, while maralixibat demonstrated a safety profile consistent with our prior clinical experience. More broadly, EXPAND adds 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 cholestatic pruritus, regardless of the underlying disease. Now I'll turn it back to Chris.