Roivant Sciences (ROIV) Study Update summary

Program Introduction and Rationale

• Mosliciguat is a once-daily, inhaled soluble guanylate cyclase (sGC) activator targeting pulmonary hypertension associated with interstitial lung disease (PH-ILD), a large population with high unmet need and limited treatment options, affecting up to 200,000 patients in the US and Europe.

• The drug is designed for direct lung delivery via dry powder inhaler, minimizing systemic side effects and V/Q mismatch, and offers anti-inflammatory and anti-fibrotic benefits beyond vasodilation.

• Mosliciguat's mechanism allows it to work independently of heme and nitric oxide, maintaining efficacy in oxidative environments common in PH-ILD.

• The product was in-licensed from Bayer by Pulmivant/Roivant, with robust IP protection extending to 2042 and additional patents expected into the mid-2040s.

• The collaboration with Bayer involves a $14 million upfront payment, up to $280 million in milestones, and tiered royalties, with no equity or other considerations.

Clinical Data and Competitive Landscape

• Phase 1b ATMOS study data showed mosliciguat achieved up to ~38% mean-max reduction in pulmonary vascular resistance (PVR), among the highest seen, with a favorable safety profile in 170 subjects dosed.

• Mosliciguat’s single-dose PVR reduction exceeded 30%, outperforming both approved and investigational therapies, including TYVASO and riociguat, and is expected to show even greater efficacy with repeat dosing.

• Safety data revealed no significant changes in blood pressure or heart rate, minimal cough, and mild adverse events, contrasting with high rates of cough and discontinuation seen with inhaled prostacyclins.

• Mosliciguat’s inhaled, lung-targeted delivery avoids systemic vasodilation, a key advantage in PH-ILD where systemic agents have failed due to oxygenation risks.

• The competitive landscape includes TYVASO, seralutinib, and Merck’s MK-5475, but mosliciguat is differentiated by its efficacy, safety, convenience, and first-in-class inhaled activator status.

Phase II Study Design and Development Strategy

• The global Phase 2 PHocus/FOCUS study will imminently enroll ~120 PH-ILD patients, using a 2:1 randomization (drug:placebo), with rapid uptitration to maximum dose and a 24-week blinded period.

• The primary endpoint is PVR change at week 16, with secondary and exploratory endpoints including six-minute walk test, NT-proBNP, and time to clinical worsening.

• Enrollment criteria require elevated baseline PVR (>4 Wood units), allow background PDE5 use, but exclude current TYVASO use; prior TYVASO exposure is permitted.

• The study is designed for efficiency, with the expectation that a single registrational trial could suffice for approval, following the precedent set by TYVASO.

• Expansion into other pulmonary hypertension subtypes is possible, but current focus remains on PH-ILD due to its large market and clear regulatory path.