ChemoCentryx Inc. agreed to advance a preclinical-stage chemokine receptor program in concert with Forest Laboratories Inc.
The new partners will collaborate to develop small-molecule therapeutics for autoimmune and inflammatory disorders such as rheumatoid arthritis and multiple sclerosis with a focus on CCR1, a chemokine receptor involved in inflammation. The program's most advanced compound, CCX634, could enter Phase I studies within the next year.
"I think Forest is looking for ways not only to expand its pipeline, but to reach farther back into the pipeline progression," ChemoCentryx President and CEO Thomas Schall told BioWorld Today. "They were seeking a number of potential opportunities in the earlier spectrum, including late preclinical-stage types of partnerships, and I think we helped fill that niche for them with a very high-value program."
The New York-based pharmaceutical firm gained a worldwide license to ChemoCentryx's small-molecule candidates, and will take the lead role in the drugs' subsequent clinical development and commercialization. More specifically, Forest will provide funding for a joint research program for up to three years, during which it will have exclusive rights to all subsequently developed CCR1 antagonists.
"CCR1 has been validated in both preclinical and animal models of arthritis," Schall said, "and there is some emerging human data both at the tissue level and at a level of looking at patients and the involvement of CCR1 in regulating immune cell trafficking in the joint space. We believe that the distribution of CCR1 on inflammatory cells that are highly relevant to the pathology of rheumatoid arthritis makes it an ideal target."
For its part, privately held ChemoCentryx will receive an up-front payment in the form of an undisclosed amount of cash coupled with an equity investment from Forest, which is purchasing preferred stock as part of the transaction.
Data from pharmacokinetic and toxicity studies proved eye-catching to potential partners, said Markus Cappel, ChemoCentryx's vice president of business development. While other suitors came to the company with interest in an alliance, he said Forest offered the best direction to move the program forward, given its track record in clinical development, regulatory proceedings and marketing. Cappel also pointed to a synergy between his company's chemokine-related research and Forest's keen interest in chemokines and the CCR1 receptor.
"The chemokine system really acts as a master controller of the broader immune response," Schall said. "So in any autoimmune or chronic inflammatory pathology, there's likely to be some chemokine-chemokine receptor interaction that can be targeted."
He stressed that targeting such receptors is a very specific process, avoiding interaction with and suppression of the rest of the immune system. In vivo findings have elucidated CCX634's high selectivity for its target receptor.
Schall noted that though the lead compound is qualified and validated, it still needs to go through further studies to facilitate an investigational new drug application, as well as scale-up processes related to manufacturing. San Carlos, Calif.-based ChemoCentryx and Forest will cooperate on further late preclinical development.
ChemoCentryx, which has raised about $51 million to date through venture capital financing and government grants, also will receive research and milestone payments, as well as "significant" royalties for resultant products. The company retains an option to co-fund certain U.S. clinical development activities, which would increase its royalties on U.S. sales, as well as an option to co-promote products to certain U.S. physician specialists.
"The partners have done extensive due diligence before entering the collaboration," Cappel told BioWorld Today. "I think this clearly shows that we can come to our partner with what we call a pharma-quality-like compound that allows them to move this into the clinic as expeditiously as possible."
Beyond its new relationship with Forest, ChemoCentryx's lead compound is the subject of a partnership with Tularik Inc. An oral treatment for psoriasis, T487 is in a Phase II study under the direction of its South San Francisco-based partner. The compound descended from another discovered by ChemoCentryx, CCX395. Tularik also plans to begin a Phase II study to evaluate whether T487's target plays a role in rheumatoid arthritis.
Elsewhere in its pipeline is Traficet-EN, an orally active drug it has advanced into Phase I trials for inflammatory bowel disease. The product targets a chemokine receptor protein implicated in Crohn's disease and ulcerative colitis, the two principal forms of inflammatory bowel disease. Schall said the product would move into Phase IIa studies later this year.
Other programs include emerging drug candidates for cancer. Named the CCX700 series, the molecules target a chemokine receptor recently identified at ChemoCentryx that Schall said controls vascular genesis of tumors during their formation. He added that the program could lead to clinical-stage studies late next year.
Earlier-stage research is focused on other chemokine receptor targets, and small molecules specific to them, for cardiopulmonary inflammation and skin diseases.