Cytokine PharmaSciences Inc (KING OF PRUSSIA, Pennsylvania), a privately-held, global biopharmaceutical company, announced development of an orally active form of semapimod, its anti-inflammatory cytokine compound. Semapimod, a synthetic guanylhydrazone that inhibits the activity of various kinases including Raf kinase (a key enzyme in the MAPK/ERK signal transduction pathway), is a potential treatment for inflammatory and autoimmune diseases such as rheumatoid arthritis, Crohn's, and psoriasis.

Semapimod has previously been tested in clinical trials only as an intravenous (IV) infusion and the newly developed oral form is hoped to significantly enhance its acceptability to patients and physicians. Despite early signals of efficacy, the phase II studies the company conducted in Crohn's disease were dose-limited by local reactions (ie, phlebitis) to the semapimod-HCl formulation. These reactions led to the need to develop a less irritating IV form, thus the company responded by developing a new salt form of semapimod with a dramatically improved solubility and tolerability profile, ultimately resulting in the new orally available formulation. The new oral form of semapimod has demonstrated its ability to reduce cytokine levels in a preclinical sepsis model. Cytokine PharmaSciences recently obtained a patent (US Pat. No. 7,244,765; July 17, 2007) on these new salts, giving considerable patent life for the reformulated product. The company is ready to move these new salts into clinical trials and is seeking a partner to assist with its development plan.

Semapimod's inhibition of Raf kinase decreases phosphorylation of MEK, thereby also inhibiting phosphorylation of p38 MAP kinase. This halts production of several important inflammatory cytokines, including TNF-α, IL-1, and IL-6. Preclinical studies have demonstrated semapimod's efficacy in animal models of inflammatory and proliferative diseases, including endotoxic shock and toxicity, pancreatitis, ischemia and stroke, necrotizing enterocolitis, and neointimal formation.

Cytokine PharmaSciences licenses technologies from academia and other sources, develops products from those technologies and out-licenses the products to third parties for marketing.