Chris Peetz
Analyst · SVB Leerink. Mari, your line is open. Please proceed with your question
Thanks, Ian. Good morning or good afternoon to everyone. Thanks for bearing with our technical difficulties getting kicked off. With our PDUFA date of September 29 for maralixibat, our focus is squarely on the realization of this upcoming potential launch. Alagille syndrome is the leading genetic cause of pediatric liver transplant, many of these driven by the severe pruritus and systematic burden of disease. And these patients are waiting for new treatment options. We estimate that Alagille syndrome alone may be a more than $500 million opportunity for maralixibat, and we are launch-ready and now have assembled the team and financial resources for successful commercialization, all while expanding our pipeline of potentially registrational studies in other rare liver diseases. Mirum is focused on advancing life-changing medicines. Today, we will recap and provide context around some of our most exciting recent steps as we continue to realize our vision of being the leading rare liver disease company. I will cover our regulatory and pipeline updates as well as the additional value we continue to build within Mirum’s clinical programs. Peter will share updates on commercialization and Ian will summarize our financial highlights. With our PDUFA date for maralixibat in cholestatic pruritus associated with Alagille syndrome next month, our team is ready to launch upon a potential approval. Our regulatory review remains on track, and we’ve been able to accommodate all inspections to date, and the FDA has continued to indicate no plans for an advisory committee. If approved in the U.S., maralixibat would serve as the first treatment approved for patients with Alagille syndrome. In the ICONIC study, which served as our pivotal study, highly significant improvements in pruritus were observed with more than 80% of participants achieving a 1 point reduction in score. We have 6 years of follow-up data and see durable responses in trial participants across the extensions of all 3 randomized studies of maralixibat in Alagille syndrome. An approval and subsequent commercial launch would mark an important milestone for Mirum and more critically, an important milestone for patients living with this terrible disease. We remain committed to further building on the body of evidence supporting maralixibat potential in Alagille syndrome. In June, we presented an integrated safety analysis of maralixibat in patients with alagille syndrome at the EASL Congress. These data resulted from 5 years of maralixibat treatment across 86 patients and continues to reinforce our understanding of the drug’s safety and tolerability profile in patients with alagille syndrome. Maralixibat was well tolerated in these patients for more than 5 years with the most common treatment-emergent adverse events reported in diarrhea and abdominal pain. In ICONIC, diarrhea incidence was at similar rates between maralixibat and placebo during the placebo-controlled portion of the study. Also in June, we presented maralixibat transplant-free survival data for progressive familial intrahepatic cholestasis Type 2 or PFIC2 at the World Congress of Pediatric Gastonerology, Hepatology and Nutrition Annual Meeting. As detailed in our presentation, maralixibat treated patients who achieved 75% serum bile acid reductions were shown to have 100% 5-year native liver survival. These PFIC2 data are under review with the European Medicines Agency. Building on that, our Phase 3 MARCH-PFIC study continues to advance well, with greater than 65 patients randomized with PFIC subtypes 1, 2, 3 and 4 across two cohorts. As a reminder, MARCH-PFIC evaluates a higher dose of maralixibat and has been shown to drive greater bile acid serum. We plan to extend enrollment and expect top line data in the second quarter of 2022. Further broadening our efforts in pediatric liver disease, our Phase 2b EMBARK study evaluating maralixibat and biliary atresia is progressing nicely as well, and we anticipate top line data in 2023. In adult liver disease, we are excited about advancing our clinical programs for volixibat, which we believe is another potentially transformative treatment for several cholestatic liver diseases. Earlier this year, we launched a Phase 2b VISTAS study for adults with primary sclerosing cholangitis and the Phase 2b OHANA study that will evaluate volixibat in intrahepatic cholestasis of pregnancy. A Phase 2b study in primary biliary cholangitis is targeted for later this year. We have incorporated regulatory feedback into the design of these volixibat studies, all of which are potentially registrational. We expect interim analyses for the VISTAS and OHANA studies to occur next year. And before handing off to Peter to discuss launch readiness, I want to touch on Mirum’s commitment to ensuring broad global access to maralixibat for alagille syndrome patients. To facilitate the international reach of maralixibat, we recently entered into an exclusive licensing agreement with GC Pharma to develop and commercialize maralixibat in South Korea. This builds on our partnership with Cambridge Pharmaceuticals in Greater China, which we announced in April. Both GC Pharma and Cambridge are leaders in rare disease and share our passion to advance life-changing medicines and we will pursue expedited approval pathways for maralixibat for Alagille syndrome based on our U.S. filing package. We see the high interest level of our partners as testament to the potential of maralixibat for pediatric cholestasis patients. On that note, I will turn it over to Peter, who will provide an overview of our launch readiness activities. Peter?