Biotie Therapies Corp (TURKU, Finland), a drug development company focusing on inflammatory diseases, dependence disorders, and thrombosis, announced top-line data from the, targeting vascular adhesion protein-1 (VAP-1). Agents that block VAP-1 interfere with leukocyte adhesion and migration and thus inhibit the cycle of inflammation. The study, conducted in a clinical pharmacology unit in the United Kingdom, investigated the safety, tolerability, and pharmacokinetic characteristics of single intravenous doses of the antibody in healthy volunteer subjects.
 
A total of 35 subjects were enrolled into the placebo-controlled study, 29 of whom received BTT-1023. The antibody was generally well tolerated and no serious adverse events were reported. Among the five subjects who received the highest dose, facial flushing was reported by two subjects with accompanying facial edema in one of the two. These were reported during or shortly after the infusion and, according to Biotie, are not uncommon events in association with intravenous administration of therapeutic protein drugs. No cytokine release or fever was observed in any subject. All adverse events were fully reversible and required no particular intervention.
 
Based on the positive data, Biotie intends to proceed to clinical studies with repeated doses of the antibody. The studies will be carried out in rheumatoid arthritis (RA) and psoriasis patients to establish appropriate dosing regimens for subsequent therapeutic studies and to provide initial information on the agent’s therapeutic potential. The dosing studies are expected to start at the end of 2008.
 
Biotie and F. Hoffmann La Roche have signed an option agreement for the antibody program targeting VAP-1. Under the terms of the agreement, Roche has paid an option initiation fee that grants it an exclusive, worldwide license agreement, excluding Japan, Taiwan, Singapore, New Zealand, and Australia where Seikagaku Corp has  licensed the product rights. The initial option right will end upon completion of phase I studies, which Roche may extend to later development points by paying additional fees.

VAP-1 is a homodimeric glycoprotein that belongs to a unique subgroup of cell-surface-expressed oxidases. VAP-1 is expressed on activated vascular endothelial cells and is involved in leukocyte adhesion and migration out of the circulation and into peripheral tissues. VAP-1 is upregulated during inflammation. Pathological accumulation of leukocytes in tissue is a common feature in many autoimmune diseases, such as RA, ulcerative colitis, and psoriasis.

VAP-1 belongs to a group of enzymes called semicarbazide sensitive amine oxidases (SSAOs). In humans and mice, three SSAOs are known: VAP-1, diamine oxidase, and retina-specific amine oxidase. Roche holds an exclusive option right to Biotie's VAP-1 SSAO enzyme small molecule inhibitor candidates in preclinical development.