Roivant Sciences (ROIV) Status Update summary

Program Overview and Clinical Rationale

• Brepocitinib is a first-in-class dual selective TYK2/JAK1 inhibitor, aiming to set a new standard of care for dermatomyositis and other autoimmune diseases, with a pivotal VALOR study readout expected in 2H 2025.

• The molecule has demonstrated robust efficacy and a well-established safety profile in over 1,500 patients across multiple positive phase II studies for various autoimmune indications.

• The VALOR trial is the largest dermatomyositis (DM) study ever, enrolling 241 patients globally, focusing exclusively on DM with both skin and muscle involvement.

• Brepocitinib’s dual inhibition targets key cytokine pathways implicated in DM, potentially offering broader efficacy than single JAK or monoclonal antibody therapies.

• Upcoming milestones include VALOR readout, proof-of-concept data in cutaneous sarcoidosis, and pivotal data in non-infectious uveitis through 2027.

Disease Burden and Unmet Need

• DM affects 40,000–50,000 US adults, causing significant disability, muscle weakness, pain, and reliance on mobility aids.

• Over 80% of DM patients receive chronic high-dose steroids, leading to major adverse effects such as osteoporosis, diabetes, infections, and mood disorders.

• Current therapies, including steroids and immunosuppressants, are often inadequate, with many patients experiencing persistent symptoms, flares, and side effects.

• DM skin disease severely disrupts quality of life, with 82% reporting daily life disruption and 65% experiencing emotional symptoms.

• There is a critical need for new, effective, and safer treatments, as no modern approved therapies exist for DM.

VALOR Study Design and Endpoints

• The trial tests two doses of brepocitinib (15 mg and 30 mg) versus placebo over 52 weeks, with a mandatory steroid taper to minimize placebo response and assess steroid-sparing effects.

• Primary endpoint is mean Total Improvement Score (TIS) at week 52; secondary endpoints include responder rates (TIS 40/60), time to response, and steroid reduction benchmarks.

• Additional endpoints include CDASI for skin disease and DMOMS for combined skin and muscle assessment.

• VALOR is 90% powered to detect a clinically meaningful difference in TIS between brepocitinib and placebo.

• The study mandates steroid tapering, with >85% of patients achieving >50% reduction and >40% eliminating steroids entirely.