BioCryst Pharmaceuticals, Inc (BIRMINGHAM, Alabama), a leader in the use of crystallography and structure-based drug design for the development of novel therapeutics, announced the initiation of the first phase II study to evaluate BCX-4208/R3421, an orally available, small molecule, second generation transition-state analog inhibitor of purine nucleoside phosphorylase (PNP). Patients with moderate-to-severe plaque psoriasis will be treated with BCX-4208, an enzyme essential for the proliferation of activated T-cells with the potential to address unmet medical needs for a broad spectrum of autoimmune diseases as well as for acute transplant rejection.

The phase II study is a double-blind, placebo-controlled, randomized trial, comprising three arms, each enrolling 20 patients with moderate-to-severe psoriasis. Two arms will receive the active drug in different dosage strengths, and patients in the third arm will receive placebo. Patients in all three arms will be dosed once daily for 6 weeks. The study, led by Roche Pharmaceuticals, will be conducted at multiple centers across the US.

BCX-4208 was originally licensed from Albert Einstein College of Medicine of Yeshiva University, in New York City, and from Industrial Research, Ltd, in New Zealand. In 2005, BioCryst announced a partnership with Roche to develop and commercialize BCX-4208 for the treatment of T-cell-mediated autoimmune diseases and acute rejection in transplantation. Roche holds exclusive worldwide rights to BCX-4208, and BioCryst retains copromotion rights in the US for several indications.

Inhibition of PNP produces selective suppression of T-cells without significantly impairing the function of other cells. Inhibition and/or elimination of activated T-cells could have a significant beneficial effect on autoimmune diseases such as psoriasis, rheumatoid arthritis, multiple sclerosis, and Crohn's disease, which appear to have activated T-cells as a major part of their pathogenesis. According to BioCryst, the potency of BCX-4208 has the ability to modulate T-cell activity for an extended period of time and thus might be suited for the treatment of diseases requiring long-term, chronic administration of a PNP inhibitor.

—A. Techman