BEIJING & CAMBRIDGE, Mass.– CANbridge Pharmaceuticals, Inc. (“CANbridge,” stock code 1228.HK), a China-based global biopharmaceutical company committed to the research, development and commercialization of transformative rare disease and rare oncology therapies, announced top-line results from a Phase 1 single ascending dose (SAD) study of CAN106, a novel, long-acting, anti-C5 complement recombinant human monoclonal antibody that is under development for the treatment of complement-mediated diseases, in 31 healthy volunteers in Singapore. This placebo-controlled study sequentially enrolled six dose cohorts (0.25, 0.75, 2, 4, 8, and 12 mg/kg CAN106) that were followed for at least 112 days. CAN106 was shown to be safe and well-tolerated with mostly mild or moderate adverse events and no drug-related serious adverse events (SAEs).
CAN106 showed dose-dependent and linear pharmacokinetic exposure with low inter-subject variability and a terminal elimination half-life of approximately 32 days. Within 24 hours of dosing, CAN106 led to dose-dependent reduction in free C5, a key complement protein required for activation of the terminal complement pathway, as well as inhibition of CH50, an ex vivo assay of serum hemolytic activity that measures the activity of the classical and terminal complement pathways. All subjects in the highest two dose cohorts (8 and 12 mg/kg) showed >99% reduction in free C5. Subjects in these two cohorts also had a >90% inhibition of CH50, which was sustained for 2 to 4 weeks, with the majority reaching the lower limit of CH50 activity quantification. The threshold of CH50 >90% inhibition has been used to indicate complete blockade of the classical and terminal complement pathways (Peffault de Latour R et al., Blood. 2015;775-783). The complement system is part of the innate immune system, which when dysregulated, is implicated in the pathophysiology of multiple rare diseases. C5 is a clinically validated target for several of complement-mediated diseases.
CANbridge has received an Investigational New Drug (IND) approval in China to commence a Phase 1b/2 study of CAN106 in patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare, acquired, and life-threatening disease in which the complement system destroys red blood cells (hemolysis). Market access to anti-C5 therapies is limited in many parts of the world. In China, there are currently no approved long-acting treatments for PNH. CAN106 was co-developed with WuXi Biologics under a rare disease strategic partnership. CANbridge holds the exclusive global development and commercialization rights and plans to develop CAN106 globally for PNH, as well as for other complement-mediated diseases which involve the activation of the C5 protein.
“We are extremely encouraged by this strong data showing that CAN106 was safe, well-tolerated and reduced free C5 levels in healthy volunteers by more than 99%, while also inhibiting CH50 by more than 90%,” said James Xue, Ph.D., Founder, Chairman and CEO, CANbridge Pharmaceuticals Inc. “These results suggest complete functional blockade of terminal complement activity, and importantly, provide the first human data validating CAN106 as a potential treatment for complement-mediated diseases. We look forward to advancing CAN106 in PNH as a first-in-class treatment in China, and as a best-in-class treatment in many markets, where PNH treatment options are few, and to expand CAN106 clinical development globally for other complement-mediated disease indications as either a first-in-class or best-in-class therapy.”
“The results of this Phase 1 compare well with other anti-C5 therapies and support the further clinical development of CAN106 in patients with PNH,” said Gerry Cox, M.D., Ph.D., Chief Development Strategist and Acting Chief Medical Officer at CANbridge. “CAN106 appears to have a favorable safety profile, high potency, and a long half-life supporting a potential extended dosing interval in PNH patients. CAN106 could provide a meaningful treatment option for PNH patients in China, where the standard of care is primarily steroid therapy, and in rare cases, bone marrow transplantation. There are no long-acting anti-C5 therapies approved in China, and market access is limited in many other countries as well.”
