Positive preliminary clinical results of Beihai Kangcheng complement inhibitor

Recently, Beihai Kangcheng announced that its long-acting recombinant humanized monoclonal antibody CAN106 targeting complement protein C5 has achieved positive top-line results in a single-dose-ascending (SAD) Phase 1 clinical trial
.
Data The study data demonstrated the effective blockade of complement C5 by CAN106, and it was safe and well tolerated and was approved by the NMPA for a phase Ib/II clinical trial for the treatment of paroxysmal nocturnal hemoglobinuria (PNH)
.
Thirty-one healthy volunteers were randomized into six dose groups (0.
25, 0.
75, 2, 4, 8, and 12 mg/kg CAN106) and followed for at least 112 days
.
The final results confirmed that CAN106 was safe and well tolerated with no drug-related serious adverse events (SAEs)
.
CAN106 showed good dose-dependent and pharmacokinetic properties with a terminal elimination half-life of approximately 32 days
.
CAN106 resulted in a dose-dependent reduction in free C5, a key protein required for activation of the terminal complement pathway, and potent inhibition of CH50 within 24 hours after administration
.
All subjects in the highest two dose groups (8 and 12 mg/kg) showed >99% reduction in free C5
.
Subjects in both cohorts also had >90% inhibition of CH50, and this inhibition persisted for 2 to 4 weeks
.
A CH50>90% inhibition threshold indicates complete blockade of the classical terminal complement pathway
.
(Peffault de Latour R et al.
, Blood.
2015; 775-783)
.
The complement system is a part of the innate immune system, and many rare diseases are related to the dysregulation of the complement system.
C5 is a clinically proven effective target for the treatment of diseases related to the dysregulation of the complement system
.
At the same time, Beihai Kangcheng's clinical trial application in China has been approved to conduct a phase Ib/II trial for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in China
.
PNH is a deadly rare disease in which hemolysis occurs due to dysregulation of the complement system, destroying red blood cells
.
In many countries, anti-C5 treatment options are limited, and in China, there is currently no approved long-acting antibody therapy for PNH
.
Beihai Kangcheng and WuXi Biologics jointly developed CAN106 under the framework of the rare disease strategic partnership
.
Beihai Kangcheng holds the exclusive global development and commercialization rights to CAN106 and plans to develop CAN106 globally for PNH and other complement-mediated diseases involving C5 protein activation
.
Xue Qun, Ph.
D.
, founder, chairman and CEO of Beihai Kangcheng, said, "These strong data demonstrate that CAN106 is safe and well-tolerated, reducing C5 levels to over 99% in healthy volunteers, while maintaining Inhibits CH50 by >90%
.
We are very encouraged
.
These results demonstrate complete functional blockade of the C5-mediated complement system by CAN106 and, importantly, provide the first validation of CAN106 as a potential treatment for complement-mediated diseases We expect to advance CAN106
as a first-in-class PNH therapy in China and a best-in-class PNH therapy in other markets where PNH treatment options are very limited At the same time, we will also promote the global clinical
development of CAN106 in other complement-mediated diseases to become a first-in-class or best-in-class therapeutic drug
.
” Beihai Kangcheng Dr.
Gerry Cox, Chief Strategy Officer and Acting Chief Medical Officer, said: "This trial has good results compared to other anti-C5 therapies and supports further clinical studies of CAN106 in patients with PNH.

CAN106 has a favorable safety profile, high activity and long half-life.
, supporting the likely prolonged dosing interval in PNH patients
.
The standard treatment for PNH in China is mainly steroid therapy and, in rare cases, bone marrow transplantation, and CAN106 could provide a meaningful treatment option for PNH patients in China
.
There are currently no approved long-acting anti-C5 therapies in China, and in many other countries there are limited treatment options to gain market access
.
The study was titled, "Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) Study of CAN106 Intravenous (IV) Single Ascending Dose (SAD) in Healthy Subjects)", was a single-center, single-dose escalation study in 31 healthy subjects (23 receiving CAN106 and 8 receiving placebo)
.
This study was designed to evaluate the safety and tolerability of single escalating doses of CAN106, characterize the PK and PD properties of CAN106, and evaluate the immunogenicity of CAN106 injection
.
Study drug doses ranged from 0.
25 mg/kg to 12 mg/kg, with follow-up from 112 to 196 days
.
About CAN106 CAN106 is an innovative long-acting recombinant humanized monoclonal antibody that binds and neutralizes C5, a complement system protein, thereby preventing the formation of the membrane attack complex (MAC), which causes cell lysis ( destruction) and other symptoms associated with PNH
.
When C5 protein is cleaved into C5a and C5b, MAC is activated, and the specific binding of CAN106 to C5 can block this process
.
CAN106 exhibited favorable PK/PD profile, safety profile and tolerability, suggesting its potential to effectively inhibit certain complement-mediated diseases
.
About Paroxysmal Nocturnal Hemoglobinuria (PNH) Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and fatal complement system disorder
.
The complement system is a part of the immune system that removes microorganisms and damaged cells by attacking cell membranes, but imbalances in its regulation can lead to some diseases
.
PNH is a typical complement-related disorder that causes severe anemia, thromboembolism, gastrointestinal pain and dysfunction, fatigue, pulmonary hypertension, renal impairment, and ultimately death
.
It is estimated that in Western countries, 1 to 2 people per million people suffer from PNH each year
.
According to the "Guidelines for the diagnosis and treatment of rare diseases (2019 edition)", in Asia, about 10 people per million people suffer from PNH every year
.
However, the treatment options for this disease are currently only allogeneic bone marrow transplantation and anti-C5 monoclonal antibodies (eculizumab and raflizumab), and only eculizumab has been approved in China, but because of its relatively High treatment costs are still out of reach for Chinese PNH patients
.