Mirum Pharmaceuticals (MIRM) investor relations material

Study background and design

• Zilurgisertib is a selective oral ALK2 inhibitor evaluated for fibrodysplasia ossificans progressiva (FOP), a disease marked by heterotopic ossification due to ALK2 mutations.

• Phase 2 PROGRESS study included patients aged ≥12 years with active FOP and CAJIS score <24, randomized 1:1 to zilurgisertib 100 mg QD or placebo for 24 weeks, followed by an open-label extension.

• Primary endpoint was the proportion of patients with new HO lesions at week 24; secondary endpoints included number and volume of new lesions, change in total lesion volume, and number of new flares.

Patient demographics and baseline characteristics

• Mean age was 20.5 years for zilurgisertib and 22.0 years for placebo groups; majority were White or Asian.

• Baseline CAJIS scores were <18 for most patients; mean time since diagnosis was over 12 years.

• Median baseline HO lesion volume was similar between groups (270.0 cm³ for zilurgisertib, 265.6 cm³ for placebo).

Efficacy outcomes

• At week 24, 3.1% of zilurgisertib patients developed new HO lesions versus 16.7% for placebo, an 81% reduction (P=0.0986).

• Mean change in total lesion volume from baseline to week 24 favored zilurgisertib (-3.24 cm³ vs 24.64 cm³ for placebo, P=0.004).

• Fewer annualized new flares were observed with zilurgisertib (2.34 vs 4.55 for placebo by week 24).

• No patients on zilurgisertib had new lesions at week 48.