Mirum Pharmaceuticals (MIRM) Study Result summary

Interim study results and design

• Interim analyses for VISTAS (PSC) and VANTAGE (PBC) phase IIb studies of volixibat showed positive efficacy and safety outcomes, meeting prespecified thresholds for continuation and supporting advancement of both programs.

• VISTAS is a 28-week, double-blind, placebo-controlled, adaptive study in PSC; interim triggered at 45th subject's week 16 visit.

• VANTAGE mirrors VISTAS in PBC, with an open interim analysis; 30 subjects randomized across 20 mg, 80 mg, and placebo arms, and up to 200 patients planned for confirmatory analysis.

• Both studies will proceed with a 20 mg b.i.d. dose based on efficacy and safety.

• Enrollment for VISTAS expected to complete in H2 2025; VANTAGE to enroll up to 200 more patients, completing in 2026.

Efficacy outcomes

• In VANTAGE, volixibat arms showed a 3.8-point reduction in ItchRO score, a 2.3-point improvement over placebo (p=0.0026); both 20 mg and 80 mg doses showed LS mean changes of -3.84 and -3.79, p<0.0001 vs baseline.

• Statistically significant improvements in pruritus and fatigue were observed, with reductions in serum bile acids and PBC-40 fatigue domain noted.

• Pruritus reduction was rapid, observed as early as week one, with 75% of patients achieving >50% reduction in serum bile acids.

• Efficacy was consistent regardless of baseline ItchRO or alkaline phosphatase levels.

• VISTAS interim surpassed pre-specified efficacy and safety thresholds, supporting study continuation.

Safety and tolerability

• Safety profiles were comparable between 20 mg and 80 mg doses; most common event was mild to moderate, transient diarrhea (77% of volixibat arms), with one discontinuation due to diarrhea.

• Four serious adverse events occurred, including one on placebo; no new safety signals identified.

• No clinically relevant or meaningful changes in liver enzymes or laboratory tests observed.

• Nearly all patients completing the double-blind phase opted into long-term extension, indicating tolerability.

• Nonclinical data show minimal systemic exposure, supporting a favorable safety profile.