The Asia Biopharma Industry Innovation Summit 2021, hosted by Taas Labs, kicked off in Shanghai on October 28.
As an annual industry summit, T-Bio has become an annual communication feast for biomedical industry practitioners. It is committed to technological exchanges and biomedical industry development, promoting the innovation and industrial integration of biomedical innovation and scientific research forces, and further promoting the development of biomedical safety and pharmaceutical disciplines in China.
Dr. Joe ZHOU, Founder & President of Genor Biopharma, delivered an opening speech with the theme of "Current Status and Trends of Antibody Drug Development: BsAb." He shared his views on the changes in the biopharmaceutical industry, the current status of China's drug regulatory environment, and the opportunities and challenges in the development of biologic drugs. He also introduced the progress of Genor Biopharma bispecific/multi-specific antibodies.
Dr. ZHOU said that innovative drug molecules need to have a better curative effect, clearer treatment mechanism, better PK/PD characteristics, and the ability to provide new treatments. He also said that they need to be more cost-effective by adopting the most effective strategy to develop biological medicine and maximize the success rate.
In addition to considering efficacy, toxicity, CMC and molecular immunogenicity, the R&D of bispecific/multi-specific antibodies should be further refined into more aspects such as functionality, affinity, titer (the number of antigen binding sites), antigen properties, antibody size, Fc structure and chain-related issues. This will make bispecific/multi-specific antibodies a high barrier to get over.
Currently, we have multiple bi-specific and tri-specific antibody drug candidates, the highlights among which include candidates targeting CD20/CD3(GB261), PD-L1/CD55(GB262), EGFR/c-Met/c-Met(GB263T), and Claudin 18.2/CD3(GB264), none of which currently have approved drugs worldwide and all of them have been accepted as “Late Breaking Abstracts” by 2021 AACR. Additionally, we have GB265 (PD-L1/TIGIT，BsAb) and GB266 (PD-L1/LAG3/LAG3，TsAb) newly added to our pipeline.
GB261 is a highly differentiated CD20/CD3 bi-specific antibody developed in-house. GB261 is the first T-cell engager with very low CD3 binding affinity and maintaining Fc effector functions (ADCC and CDC). With similar binding affinity to CD20 as rituximab, GB261 significantly inhibits rituximab-resistant cancer cell proliferation by in vitro assays and in vivo models.
More importantly, GB261 induces low levels of cytokine production by hPBMC and in monkeys, indicating low occurrences of CRS. Thus, GB261 is a highly promising bispecific therapeutic antibody for B cell malignancies. It may ultimately provide a concept shift to better and safer T-cell engager antibody drugs for various cancers.
GB263T has been designed as a tri-specific antibody targeting EGFR and two different cMet epitopes. The tri-specific antibody has two Fabs to bind EGFR. Its Fc fragment has been mutated to enhance Fc functions. Thus, GB263T with highly differentiated design, exhibits multiple mechanisms of action to inhibit primary and secondary EGFR mutations and cMet signaling pathway simultaneously. The significant anti-tumor activities have been demonstrated by in vitro studies and in vivo animal models.
- GB263T potently blocked ligand-induced phosphorylation of EGFR and c-Met, and demonstrated better dual inhibition of EGFR and cMet signaling pathways compared to JNJ analogue (Fig. 1).
- GB263T effectively induced internalization of EGFR and cMet, and downregulated the expression levels of both EGFR and cMet (Fig. 1).
- GB263T strongly inhibited cell growth of Ba/F3 cells harboring EGFRexon20ins (Fig. 2), and resulted in dose-dependent inhibition of tumor growth by in vivo studies (Fig. 3).
- GB263T showed remarkable ADCC effects to kill cancer cells harboring resistance mutations in EGFR with c-Met expression or amplification.
- In addition, GB263T did not show any major toxicities in monkeys, even at a high dose of 100mg/kg given weekly for 4 weeks in a pre-tox study.
There was one main forum and three sub-forums in T-Bio 2021 focusing on antibody therapeutics, cell therapy, gene therapy, rare disease treatment, immunotherapy innovation and the pain points/latest scientific technology on R&D, manufacturing and clinical medicine. It attracted more than 20 industry leaders to share their experience, insights and application cases. More than 300 decision-makers and practitioners from more than 100 global biotechnology companies and members of the biomedical industry chain discussed industry prospects and cooperation opportunities.
