Avidia, Inc. (MOUNTAIN VIEW, Calif), a privately-held biopharmaceutical company focused on discovering and developing a new class of small, assembled human therapeutic proteins called Avimers™ (from avidity multimers), announced that it has initiated dosing of the first patient for a phase I clinical trial of its Avimer drug candidate C326, an inhibitor of interleukin-6 (IL-6), for the treatment of Crohn's disease. The placebo-controlled, single– and multiple–dose-escalation study is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic profile of C326 vs placebo in adults with Crohn's disease. The trial is being conducted in Australia.

"This trial marks Avidia's transition from a research-based company to a clinical development organization, less than 2 years after we started the IL-6 inhibitor program, demonstrating the capability of our Avimer technology to deliver new therapeutic product candidates," said Peter Van Vlasselaer, PhD, Avidia's CEO.

Avimers are single-protein chains, generally smaller than 25 kD in size, and are composed of multiple, modular binding domains generated from the exon shuffling of a large family of human extracellular receptor domains. Each modular binding domain is designed to bind to a particular target site. The modular binding domains can bind simultaneously to sites on a single protein target and/or to sites on multiple protein targets. Avimers can be expressed in the cytoplasm of Escherida coli and then properly folded upon air oxidation, resulting in yields approaching 1.5 g/L in high-cell-density fermentations.

Avimer C326 consists of an immunoglobulin G (IgG)-binding domain fused to the N-terminus of a 3-domain IL-6-binding region, resulting in a 19-kDa heterotetrameric Avimer. Attachment of the IgG-binding domain confers an expected human serum half-life of ~178 hours based on allometric scaling from pharmacokinetics studies in cynomolgus monkeys, which compares favorably with the half-lives of several approved biotherapeutics and is consistent with the potential for once- or twice-monthly dosing. Each IL-6 binding domain binds independently to different epitopes on IL-6 and the energetic contributions of each domain are additive, yielding a subpicomolar IC50 in cell-based assays and a dose-dependent abrogation of the acute phase response of mice to injected IL-6. In addition to Crohn's disease, IL-6 levels are raised in a variety of autoimmune and inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, systemic onset juvenile idiopathic arthritis, and systemic lupus erythematosus.

Avimers with sub-nanomolar affinities have been obtained against four additional potential therapeutic targets: cMet, CD28, CD40L, and BAFF.

—A. Techman