Also in the area of inflammatory bowel disease, our drug candidate CCX507 is a second-generation inhibitor of the chemokine receptor known as CCR9. CCX507 is selective for CCR9 relative to all other chemokine receptors, orally bioavailable, and has an excellent preclinical safety profile. We have completed Phase I clinical development and we plan to move CCX507 forward to Phase II clinical trials, potentially in conjunction with a strategic partner.
A Phase I clinical trial of CCX507 showed that it was safe and well-tolerated in healthy volunteers at all doses tested, and blocked CCR9 on circulating leukocytes. Preclinical data have also demonstrated that CCX507, in combination with an anti-α4β7 or anti-TNF blocking antibody, markedly reduced the severity of colitis more effectively than monotherapy treatment with either drug alone.
Inflammatory bowel disease (IBD) refers to two diseases – ulcerative colitis and Crohn’s disease – both characterized by inflammation of the gastrointestinal tract. Ulcerative colitis is inflammation of the large intestine.
Building on our expertise in the area of CCR9 inhibitors and inflammatory bowel disease, we initiated a de novo discovery program under which we have designed a series of novel molecules that we believe represent the next generation of CCR9 inhibitors. Our lead next generation CCR9 inhibitor, CCX507, has demonstrated in preclinical models that combination therapy with an anti-α4β7 blocking antibody resulted in a more significant reduction in the severity of colitis than monotherapy treatment with either CCX507 or an anti-α4β7 blocking antibody alone.
Orally Administered CCR9 Inhibitor CCX507 Effectively Blocks CCR9 in Circulating Human Leukocytes. Lisa Seitz, Lisa Lohr, Joanne Tan, Antonia Potarca, Shichang Miao, Daniel J. Dairaghi, Trevor Charvat, Andrew Pennell, Penglie Zhang, Thomas J. Schall, Pirow Bekker. Presented at: Digestive Disease Week, 2013
CCX507, an Orally Bioavailable Second Generation Antagonist of the Chemokine Receptor CCR9. M. J. Walters, K. E. Ebsworth, P. Zhang, J. P. Powers, D. Dairaghi, L. Ertl, B. Zhao, Y. Wang, S. Miao, L. Lohr, J. C. Jaen, P. Bekker, T.J. Schall. Presented at the United European Gastroenterology Week Meeting, 2013
Small Molecule Inhibition of Chemokine Receptor ‘CCR9’ Combined with Anti-alpha4beta7 Blocking Antibodies Confers Synergistic Protection against Piroxicam-Accelerated Colitis in Mice. J.B.L. Tan, K.E. Ebsworth, L. Ertl, D. Canivel, P. Zhang, , P. Bekker, & T.J. Schall. Presented at the American College of Gastroenterology Meeting, 2014