JAK3 - Pharmacopeia

JAK3 - Dermatology & Ocular Disease

Need: Psoriasis is a debilitating disease resulting in significant lost time from work and often resulting in additional clinical manifestations of disease such as psoriatic arthritis. Current systemic treatments are limited by toxicity whereas current topical treatments have limited efficacy in severe disease. Dry eye is an ocular inflammation resulting in decreased production of fluids from the tear gland and causing irritation and diminished vision. Dry eyes are a common source of discomfort in adults age 40 or older.

Potential: Topical administration of a JAK3 kinase inhibitor for psoriasis could inhibit T-cell proliferation with the potential advantage of limited systemic side effects. Treatment of dry eye is aimed at reducing conjunctival inflammation and restoring normal tear film to minimize dryness. Local administration of a JAK3 kinase inhibitor would selectively reduce cytokine-induced inflammation in the conjunctiva.

Therapeutic Target: A member of the Janus family of tyrosine protein kinases, JAK3 plays a critical role in T-cell proliferation via cytokine signaling pathways. Local administration of a selective JAK3 inhibitor represents a potential therapeutic approach for T-cell and cytokine mediated dermatological and ocular diseases. These include psoriasis, which is characterized by hyper-proliferation of T-cells which present themselves in inflamed skin lesions, and dry eye, which is a cytokine-based inflammation of the ocular surface.

Program Status: Pharmacopeia has identified a series of potent JAK3 inhibitors that are immunoregulatory in preclinical models of T-cell activities. Lead candidates for psoriasis show good skin permeation. Additional studies are in progress to advance compounds toward preclinical development.

* Pharmacopeia has partnered with Wyeth for all other indications and routes of delivery.