Incyte Corp (WILMINGTON, Delaware), a drug discovery and development company with a growing pipeline of oral compounds to treat inflammation, HIV, cancer, and diabetes, announced positive clinical proof-of-concept results with its wholly-owned, internally developed, lead JAK2 (Janus-associated kinase 2) inhibitor, INCB18424, in rheumatoid arthritis (RA) and psoriasis. Incyte reported positive preliminary results obtained from an ongoing 28-day phase IIa, placebo-controlled, dose-ranging trial of oral INCB18424 in RA, and results from a 28-day phase IIa trial with the topical form of INCB18424 in mild-to-moderate psoriasis patients.

Three of four patients completing the RA study met ACR50 criteria, two of whom also met ACR90 criteria, one within 2 weeks. Two patients receiving placebo did not shown significant responses. The drug showed good tolerability at the current dose of 15 mg BID. Incyte expects to initiate a 3-month phase IIb oral RA trial in the second half of 2008.

Results from the phase IIa trial with the topical form of the agent in mild-to-moderate psoriasis patients, indicate that it provides at least comparable efficacy to the potent topical steroid, Diprolene® (betamethasone dipropionate, Schering Corp). The agent continues to be well-tolerated in this study and, assuming its safety profile continues in ongoing required safety studies, Incyte intends to begin a 3-month psoriasis phase IIb trial with topical INCB18424 in the second half of 2008, and a 28-day phase IIa trial in psoriasis with oral INCB18424 in the first half of 2008.

The JAK family comprises four nonreceptor tyrosine kinases: JAK1, 2, 3, and TYK2. JAK1, JAK2, and TYK2 are expressed in multiple tissues, whereas JAK3 is restricted to the hematopoietic system. These enzymes are critical components of signaling mechanisms utilized by a number of growth factors and cytokines (following their binding to specific receptors on the cell surface), including inflammatory cytokines such as IL-6, -12, and -23. JAKs in turn, activate the signal transducer and activator of transcription proteins that transmit the growth and activation signals to the nucleus. INCB18424 is a potent JAK1 and 2 inhibitor that is greater than 100x selective against a broad panel of kinases (including 10x to 40x selectivity over the JAK3 enzyme) and has broad applicability in a number of autoimmune diseases (where it is expected to be effective in patients refractory to anti-TNF therapies), malignant hematologic conditions, and solid cancers.