CMC Strategies For The Development Of A Bispecific Antibody Platform for Cancer Immunotherapy

By Jianzhong Hu, YZY biopharma

Compared to the development of typical monoclonal antibody (mAb) drugs, the development of bispecific antibodies (BsAbs) can present many challenges in product expression, purification, product stability, and scale up of the manufacturing process. Therefore, in addition to efforts made with molecular design, CMC strategies are critical for developing and marketing bispecific drugs.  

A Growing Future For Bispecific Antibodies

Bispecific antibodies is an emerging and potentially highly profitable area of next-generation antibody products. They are engineered immunoglobulins with the ability to bind to two different epitopes on the same or different antigens. Therapy with immunoglobulin G (IgG)-like BsAbs shows active immunization against specific tumors, which in the future could lead to increased use of this format to provide long-lasting antitumor immunity in the organism.¹

There are currently more than 200 BsAbs in clinical trials, with two already available on the market (Hemlibra and Blincyto), bringing in total sales of nearly $1 billion in 2018.² A recent analysis predicts the estimated market opportunity for BsAbs to surpass $8 billion by 2025.² The potential of BsAbs and their promise in cancer immunotherapy is garnering attention from both big and small pharma companies. Wuhan YZY Biopharma, located in Wuhan, China, has two bispecific candidates in Phase I clinical studies and several other candidates in the pre-clinical or discovery stage. Its lead product candidates were developed using YZY’s proprietary bispecific antibody platform, YBODY^®, which uses engineered Fc to promote heterodimer formation. The potency of the antibody can be greatly enhanced by recruitment of T cells.