Bispecifics are a class of engineered antibody and antibody-like proteins that can simultaneously bind to two different targets, showing promise as next generation biotherapeutics. Their potential lies in delivering a drug with two payloads, instead of one, and also in the flexibility of creating antibodies with different pairs of targets to address multitudes of treatments. However, large-scale manufacturing of bispecific biologics is more complex than regular antibody production, often ending up with low yield, aggregated or unstable products. This has posed a great challenge for the bispecifics field and has limited the development of bispecific drugs in the past two decades, with only over ten approved bispecific antibody drugs on the market today.
Through years of research, we have developed a world-class Fc-based heterodimer bispecific platform called CRIB (Charge Repulsion Induced Bispecific) to overcome CMC (Chemistry, Manufacturing and Control) issues for Fc based bispecifics. It is our belief that the closer the structure of a bispecific is to a natural antibody, the better for manufacturing of bispecifics. The CRIB platform enables the formation of a bispecific antibody with identical format and size of a regular antibody.
Adjust multiple different interactions
Break down homodimer interaction
No in vitro reconstitution – straightforward production
KN026 is an anti-HER2 bispecific antibody independently developed by Alphamab Oncology using the proprietary Fc-based heterodimer bispecific platform technology (CRIB). KN026 can bind two non-overlapping epitopes of HER2 simultaneously, leading to a dual HER2 signal blockade, and the molecular structure is identical to that of a natural IgG antibody. KN026 is produced using conventional antibody manufacturing processes, with product yield and quality reaching leading levels.
* Wei H, Cai H, Jin Y, et al. Structural basis of a novel heterodimeric Fc for bispecific antibody production. Oncotarget, 2017, 8(31): 51037.
