CCX507 Reduces Colitis in Inflammatory Bowel Disease Models
MOUNTAIN VIEW, CA and ORLANDO, FL, USA UI May 21, 2013 I ChemoCentryx, Inc. (CCXI) announced data showing that CCX507, a next generation orally available inhibitor of the chemokine receptor known as CCR9, exhibited excellent pharmacokinetics and was well tolerated in a Phase I trial in healthy subjects. Preclinical data were also presented, showing that CCX507 markedly inhibited the recruitment of T cells to the intestine and significantly reduced colitis and colitis-associated wasting in inflammatory bowel disease models. The data, which were presented in a poster presentation at the Digestive Disease Week 2013 conference in Orlando, further strengthen the rationale for the use of a CCR9 antagonist in inflammatory bowel disease (IBD).
“We are encouraged by both the clinical and preclinical data for CCX507, which further highlight the potential utility of CCR9 inhibitors in inflammatory bowel disease,” said Thomas J. Schall, PhD, President and Chief Executive Officer of ChemoCentryx. “Given our expertise in the CCR9 and IBD field, we believe that CCX507, which was discovered and developed by ChemoCentryx researchers, provides another potent and selective compound to our CCR9 franchise and to the ChemoCentryx portfolio. We look forward to continued development of CCX507 and maximizing its potential as an important new treatment option for IBD.”
The chemokine receptor known as CCR9 and its chemokine ligand, CCL25 (also called TECK), play a key role in attracting inflammatory cells to inflamed GI tissue. Previous studies have demonstrated the therapeutic potential of CCR9 inhibition, including studies with the Company’s most advanced drug candidate, vercirnon (also known as Traficet-EN(TM), CCX282 or GSK1605786), which showed that the CCR9 inhibitor was effective in the treatment of moderate-to-severe Crohn’s disease patients, including those with colonic involvement. Vercirnon, now partnered with GlaxoSmithKline, is in four Phase III clinical trials, with data expected from the pivotal SHIELD-1 Phase III clinical trial expected in the second half of 2013. The de novo CCR9 inhibitor CCX507 is wholly owned by ChemoCentryx.
Phase I CCX507 Clinical Results
In the Phase I single-ascending dose study, healthy patients were given three different doses of CCX507: 3 mg, 10 mg, or 30 mg. CCX507 exhibited dose-proportional pharmacokinetics, and appeared to be well tolerated. No serious adverse events were reported, and no withdrawals from the trial due to adverse events were reported.
Preclinical CCX507 Results
ChemoCentryx reported positive preclinical results for CCX507 in three separate models of IBD. Employing an adoptive transfer model utilizing mice expressing a large proportion of T cells that recognize a single defined antigen stimulus, CCX507 administration resulted in a significant reduction in the number of intra-epithelial lymphocytes (IELs) in the intestine after an oral challenge with the defined antigen. Also, in a genetic model of colitis, CCX507 treatment reduced the extent of weight loss resulting from the disease, and significantly reduced the inflammatory and fibrotic changes to the colon over several months of treatment. Finally, in a T cell transfer model of colitis, CCX507 also protected against weight loss and colon inflammation when compared to vehicle (placebo) treated controls. The Company’s researchers also noted that in both human and in animal models, the chemokine protein that binds and activates CCR9 (the chemokine known as CCL25 or TECK), was present in colon tissue and was markedly upregulated in colon tissue from patients with colitis, and also in animals that were advancing from mild to severe disease.
About ChemoCentryx
ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer. The chemokine system is a biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. The Company’s most advanced drug candidate, vercirnon (also known as Traficet-EN, CCX282 or GSK1605786), a specific CCR9 inhibitor, completed a multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn’s disease, where it demonstrated the ability to induce a clinical response and to maintain clinical remission, and is now in Phase III clinical development. The Company’s lead independent drug candidate, CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. Other clinical programs include CCX354 (also known as GSK2941266), a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis, CCX168, a C5aR inhibitor in Phase II clinical development for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, as well as CCX872, a CCR2 inhibitor, and CCX507, an inhibitor of CCR9, both of which are in Phase I clinical testing. ChemoCentryx also has several programs in advanced preclinical development.
SOURCE: ChemoCentryx
Post Views: 90
CCX507 Reduces Colitis in Inflammatory Bowel Disease Models
MOUNTAIN VIEW, CA and ORLANDO, FL, USA UI May 21, 2013 I ChemoCentryx, Inc. (CCXI) announced data showing that CCX507, a next generation orally available inhibitor of the chemokine receptor known as CCR9, exhibited excellent pharmacokinetics and was well tolerated in a Phase I trial in healthy subjects. Preclinical data were also presented, showing that CCX507 markedly inhibited the recruitment of T cells to the intestine and significantly reduced colitis and colitis-associated wasting in inflammatory bowel disease models. The data, which were presented in a poster presentation at the Digestive Disease Week 2013 conference in Orlando, further strengthen the rationale for the use of a CCR9 antagonist in inflammatory bowel disease (IBD).
“We are encouraged by both the clinical and preclinical data for CCX507, which further highlight the potential utility of CCR9 inhibitors in inflammatory bowel disease,” said Thomas J. Schall, PhD, President and Chief Executive Officer of ChemoCentryx. “Given our expertise in the CCR9 and IBD field, we believe that CCX507, which was discovered and developed by ChemoCentryx researchers, provides another potent and selective compound to our CCR9 franchise and to the ChemoCentryx portfolio. We look forward to continued development of CCX507 and maximizing its potential as an important new treatment option for IBD.”
The chemokine receptor known as CCR9 and its chemokine ligand, CCL25 (also called TECK), play a key role in attracting inflammatory cells to inflamed GI tissue. Previous studies have demonstrated the therapeutic potential of CCR9 inhibition, including studies with the Company’s most advanced drug candidate, vercirnon (also known as Traficet-EN(TM), CCX282 or GSK1605786), which showed that the CCR9 inhibitor was effective in the treatment of moderate-to-severe Crohn’s disease patients, including those with colonic involvement. Vercirnon, now partnered with GlaxoSmithKline, is in four Phase III clinical trials, with data expected from the pivotal SHIELD-1 Phase III clinical trial expected in the second half of 2013. The de novo CCR9 inhibitor CCX507 is wholly owned by ChemoCentryx.
Phase I CCX507 Clinical Results
In the Phase I single-ascending dose study, healthy patients were given three different doses of CCX507: 3 mg, 10 mg, or 30 mg. CCX507 exhibited dose-proportional pharmacokinetics, and appeared to be well tolerated. No serious adverse events were reported, and no withdrawals from the trial due to adverse events were reported.
Preclinical CCX507 Results
ChemoCentryx reported positive preclinical results for CCX507 in three separate models of IBD. Employing an adoptive transfer model utilizing mice expressing a large proportion of T cells that recognize a single defined antigen stimulus, CCX507 administration resulted in a significant reduction in the number of intra-epithelial lymphocytes (IELs) in the intestine after an oral challenge with the defined antigen. Also, in a genetic model of colitis, CCX507 treatment reduced the extent of weight loss resulting from the disease, and significantly reduced the inflammatory and fibrotic changes to the colon over several months of treatment. Finally, in a T cell transfer model of colitis, CCX507 also protected against weight loss and colon inflammation when compared to vehicle (placebo) treated controls. The Company’s researchers also noted that in both human and in animal models, the chemokine protein that binds and activates CCR9 (the chemokine known as CCL25 or TECK), was present in colon tissue and was markedly upregulated in colon tissue from patients with colitis, and also in animals that were advancing from mild to severe disease.
About ChemoCentryx
ChemoCentryx, Inc. is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing orally-administered therapeutics that target the chemokine and chemoattractant systems in order to treat autoimmune diseases, inflammatory disorders and cancer. The chemokine system is a biological network that regulates inflammation via a collection of secreted chemokine molecules, or ligands, and their specific cell surface receptors. Based on its proprietary drug discovery and drug development platform, ChemoCentryx has generated multiple clinical and preclinical-stage programs, each targeting distinct chemokine and chemoattractant receptors with different small molecule compounds. The Company’s most advanced drug candidate, vercirnon (also known as Traficet-EN, CCX282 or GSK1605786), a specific CCR9 inhibitor, completed a multi-national clinical trial, called PROTECT-1, in patients with moderate-to-severe Crohn’s disease, where it demonstrated the ability to induce a clinical response and to maintain clinical remission, and is now in Phase III clinical development. The Company’s lead independent drug candidate, CCX140, a CCR2 inhibitor, has been shown to be safe and well tolerated while demonstrating clinical activity on glycemic indices in a Phase II clinical trial in type 2 diabetics, and is now in Phase II clinical development for the treatment of diabetic nephropathy. Other clinical programs include CCX354 (also known as GSK2941266), a CCR1 inhibitor which successfully completed a Phase II clinical trial for the treatment of rheumatoid arthritis, CCX168, a C5aR inhibitor in Phase II clinical development for the treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, as well as CCX872, a CCR2 inhibitor, and CCX507, an inhibitor of CCR9, both of which are in Phase I clinical testing. ChemoCentryx also has several programs in advanced preclinical development.
SOURCE: ChemoCentryx
Post Views: 90
