ChemoCentryx Announces Positive Results in Phase II ANCA-Associated Vasculitis CLEAR Trial of Orally Administered Complement 5a Receptor Inhibitor CCX168

ChemoCentryx, Inc.,

, a clinical-stage biopharmaceutical company developing orally-administered therapeutics to treat autoimmune diseases, inflammatory disorders, and cancer, today announced positive top-line data from its' Phase II CLEAR trial with CCX168 in patients with anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis, or AAV. CCX168 is a potent orally-administered small molecule that is a selective inhibitor of the complement C5a receptor, or C5aR. CCX168 is the lead drug candidate in the Company's orphan and rare disease program. The Phase II CLEAR was designed to assess whether high dose chronic steroids used in the standard of care (SOC) regimen in AAV could be sharply reduced or eliminated, without compromising efficacy, by replacement with CCX168, a specific inhibitor of the C5aR. The complement component C5a and its receptor are thought to activate the autoimmune cells that destroy the blood vessels in AAV. Steroid elimination is desirable because steroids are strongly implicated in infections and other serious adverse events resulting in premature death in AAV, as well as long term toxicities, and cumulative organ damage. The CLEAR trial met its primary endpoint based on the Birmingham Vasculitis Activity Score (BVAS) response at week 12 in patients receiving CCX168, compared to those patients receiving the high dose steroid-containing standard of care. Specifically, all treatment groups receiving CCX168 demonstrated a statistically significant (P=0.005) non-inferior clinical efficacy outcome when compared to SOC. The study contained two CCX168 treated groups: one group which received CCX168 with a low dose of steroid (i.e. one third the steroid in the SOC), in which the BVAS response was 86% at week 12 vs 75% for SOC; P=0.005 for non-inferiority. A separate group received CCX168 in the absence of any steroid; in this group the response was 81% (P=0.02 for non-inferiority). SOC treatment included a placebo to CCX168, and all treatment groups received a standard background immunosuppressant (cyclophosphamide or rituximab) as well. The primary endpoint of BVAS response was prospectively defined as a decrease from baseline of at least 50% in BVAS plus no worsening in any body system. BVAS measures AAV disease activity across all organ systems and is the most widely used and clinically validated outcome measure in AAV clinical trials. The greater the reduction in BVAS score, the greater the disease improvement. Other beneficial changes were noted, including in pre-specified secondary endpoints: CCX168 exhibited a more rapid onset of improvement than SOC treatment, as evidenced by beneficial changes in proteinuria (measured as urinary albumin:creatinine ratio, or UACR); also rapid beneficial reductions from baseline in BVAS, as well as reductions in the levels of MCP-1 (a marker of kidney inflammation) found in the urine; Improvements in estimated glomerular filtration rate (eGFR) and hematuria were seen in all three treatment groups, indicating these disease activities did not require high dose chronic steroid administration to be controlled; Improvements in "Quality of Life" (as defined by the visual analogue scale of the EuroQOL-5D-5L measurement) were seen in CCX168 treatment groups, but not in the SOC group Taken together, these results indicate that CCX168, a target-specific complement inhibitor, can replace chronic steroids in the treatment of AAV with at least equal efficacy. CCX168 also appeared safe and well tolerated in the trial. There were no observations that would prevent further clinical development of CCX168. The Company has also recently completed the long-term toxicology program with CCX168. The results provide support for chronic dosing of CCX168 in future clinical trials. "For my patients with AAV, I would absolutely welcome a safer treatment with a rapid onset of action, retained existing efficacy outcomes, and which also would enable me to eliminate steroids from the current treatment regimen," said David Jayne, M.D., from Addenbrooke's Hospital in Cambridge, UK, and the principal clinical investigator for the trial. "High dose steroids are associated with a high incidence of morbidity, including infections, and since no steroid sparing therapies are approved today, I believe that there remains a significant need for additional, safer therapeutic options for AAV patients. As a C5aR inhibitor, CCX168 also has the potential for both steroid sparing and improved long-term kidney outcomes." "We are extremely pleased with the CLEAR trial results in 67 patients with AAV, particularly the ability of CCX168 to eliminate the need for chronic steroid administration, thus greatly lessening the harmful side-effects associated with long-term steroid usage. Based on these results, we believe CCX168 could change the treatment paradigm for patients with AAV," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "This is an important milestone for ChemoCentryx. We also look forward to upcoming results from the CLASSIC trial that, together with the results from the CLEAR trial, will collectively enable End-of-Phase II meetings with regulatory authorities, and initiation of our Phase III development program later this year."