GlaxoSmithKline (GSK) (LONDON, UK) and ChemoCentryx, Inc.(MOUNTAIN VIEW, Calif.), a company focused on orally-administered, small-molecule therapeutics that target the chemokine and chemoattractant receptor systems, announced a worldwide multitarget strategic alliance to discover, develop, and market novel medicines targeting four chemokine and chemoattractant receptors for the treatment of a variety of inflammatory disorders, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), acute macular degeneration, and asthma.
ChemoCentryx will receive an upfront payment of $63.5 million comprised of cash and an equity investment in the form of a Series D financing. In addition, ChemoCentryx will receive research funding and will be eligible to earn milestone payments up to potentially $1.5 billion, across the six product options on the four targets, assuming successful development and commercialization. ChemoCentryx will also receive double-digit royalties on all collaboration product sales and will be able to increase royalties in certain instances by cofunding development through phase III clinical trials. Furthermore, under certain circumstances, upon an initial public offering by ChemoCentryx, GSK will invest in ChemoCentryx's common stock.
Under the terms of the agreement, ChemoCentryx will be responsible for the discovery and development of small molecule drug candidates targeting four specific chemokine and chemoattractant receptor targets through clinical proof-of-concept, at which point GSK will have exclusive options to license each product for further development and commercialization on a worldwide basis. The agreement encompasses ChemoCentryx's lead product candidate, Traficet-EN® (CCX282-B), a specific CCR9 (CC chemokine receptor-9) antagonist currently in a late-stage multinational clinical trial (PROTECT-1) expected to enroll more than 420 patients with moderate-to-severe Crohn's disease, as well as three ongoing pre-agreed preclinical research programs involving named but undisclosed chemokine and chemoattractant receptor targets. ChemoCentryx will retain the option to codevelop and to copromote Traficet-EN in IBD to certain physician specialists in the US.
In Crohn's disease, dysregulation of either the CCR9 chemokine receptor or its ligand, CCL25, is thought to selectively attract inflammatory T cells to, and subsequently attack, tissues in the digestive tract. In preclinical studies, Traficet-EN has shown efficacy in both therapeutic and prophylactic models of Crohn's disease and ulcerative colitis. Four phase I trials have been completed for Traficet-EN in healthy subjects showing the drug is well tolerated and appropriate for once- or twice-daily oral dosing. A double-blind, placebo-controlled, parallel group, two-stratum phase II clinical trial of the safety, tolerability, immunologic and clinical activity, and population pharmacokinetics of Traficet-EN in subjects with active, moderate-to-severe Crohn's disease demonstrated that Traficet-EN administered daily for 28 days was well tolerated and demonstrated clinical activity compared with placebo. PROTECT-1 is a 12-week, randomized, double-blind, placebo-controlled, registration-grade phase II trial, and will test three different dosing regimens of Traficet-EN. The study began in March 2006 and is expected to be completed by 2Q/2007.
ChemoCentryx has initiated a phase I clinical trial in its second clinical program that targets the chemokine receptor CCR2. The CCR2 receptor is thought to be of central importance to inflammatory diseases, such as RA, MS, pulmonary fibrosis, and kidney fibrosis, type 2 diabetes, and atherosclerosis. The company's lead development candidate for this target, CCX915, has demonstrated a favorable safety, efficacy, and pharmacokinetic profile in preclinical studies, including promising data in animal models demonstrating the potential of CCR2 in RA. Whereas MS has been selected as the lead indication for the CCR2 program, the company previously has stated its plan to pursue some of these other indications either on its own or with a development and commercialization partner.
In other preclinical stage studies, ChemoCentryx is optimizing an orally-available, highly potent and highly selective small-molecule antagonist of C5aR, the receptor for the complement protein C5a. C5a is thought to be a potent chemoattractant underlying the inflammation-induced damage in such autoimmune diseases as SLE, RA, and others. ChemoCentryx also is conducting preclinical studies of a novel, orally bioavailable, highly potent small molecule antagonist to CCR1, which binds the ligands macrophage inflammatory protein-1α (MIP-1α), RANTES, and monocyte chemotactic protein-3 (MCP-3), and is generally considered a prime therapeutic target for treating chronic inflammatory disorders such as RA and MS. Additionally, ChemoCentryx has a preclinical stage program focused on inflammatory skin disease.
Finally, ChemoCentryx simultaneously announced the recent completion of a Series C financing with participating investors including Jennison Associates LLC, HBM BioVentures, Orbimed Advisors, LLC, TECHNE Corporation, Alta Partners, and GIMV providing $17.7 million in additional capital.
— A. Techman
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