ABOUT BREPOCITINIB

Priovant’s lead molecule is brepocitinib, a potent dual inhibitor of TYK2 and JAK1. By selectively inhibiting both TYK2 and JAK1, brepocitinib is optimized to suppress signaling of a wide range of TYK2- and JAK1-dependent cytokines linked to autoimmunity, including type I and type II interferon, IL-6, IL-12, and IL-23.

Oral brepocitinib has been evaluated in 14 completed Phase 1 and Phase 2 studies, including five placebo-controlled Phase 2 studies. All five of these placebo-controlled Phase 2 studies generated statistically significant and clinically meaningful efficacy results. Oral brepocitinib’s safety database includes over 1,000 exposed subjects and suggests a safety profile similar to those of approved JAK inhibitors.

Priovant is developing brepocitinib across multiple severe autoimmune diseases with few approved therapies and pathobiologies aligned with the distinctive benefits of dually inhibiting both TYK2 and JAK1. The company’s lead indications are dermatomyositis and systemic lupus erythematosus (SLE). Priovant recently initiated VALOR, a single registrational Phase 3 study evaluating brepocitinib in dermatomyositis patients, with top-line results expected in the second half of 2025. An ongoing study in SLE designed to serve as one of two registrational studies is expected to generate top-line results in the second half of 2023. Priovant is also developing brepocitinib in hidradenitis suppurativa, an inflammatory skin disease, and non-infectious uveitis, an inflammatory ocular disease.

ABOUT DERMATOMYOSITIS

Dermatomyositis is an immune-mediated disease of the skin and muscles. Patients with dermatomyositis usually present with a characteristic skin rash and debilitating muscle weakness, which may lead to significant functional impairment and/or disfigurement. Substantially increased risk of interstitial lung disease, malignancy, and heart failure contribute to an estimated five-year mortality rate of 10-40%. Existing dermatomyositis therapies are associated with serious safety risks and burdensome administration, and many patients will not respond adequately. There is accordingly a substantial unmet need for novel, efficacious and convenient therapies that address the underlying pathophysiology of dermatomyositis.

Priovant is currently running the VALOR Study to evaluate the use of brepocitinib in dermatomyositis patients. Clinical evidence from a previous investigator-initiated study of tofacitinib, an approved JAK1/2/3 inhibitor, and over 100 off-label case reports suggests that JAK1 inhibition is efficacious in dermatomyositis. Since dermatomyositis pathobiology is driven by dysregulations in cytokines whose signaling is mediated by both TYK2 and JAK1, there may be potential for greater efficacy for brepocitinib compared to tofacitinib, selective JAK1 inhibitors, and selective TYK2 inhibitors.

ABOUT SLE

SLE is a clinically heterogeneous autoimmune disease that can impact nearly all major organ systems. While there are two approved targeted biologics for SLE, many patients respond inadequately. Like dermatomyositis, SLE pathobiology is characterized by dysregulations in type I interferon and other TYK2- and JAK1-mediated proinflammatory cytokines, suggesting that brepocitinib may be a particularly effective disease-modifying agent due to its dual inhibition of TYK2 and JAK1. Brepocitinib is currently being evaluated in an ongoing large Phase 2b study in SLE, designed to serve as one of two registrational studies. Top-line results are expected in 2H 2023.