Boan Biotech's Anti-PD-L1/TGF-β Bispecific Antibody BA1201 Approved for Clinical Trials in China

Shanghai, December 14, 2021—Luye Pharma Group announced that the clinical trial application for BA1201, an anti-PD-L1/TGF-β bispecific antibody developed by its subsidiary Boan Biotech, has been approved by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA).

BA1201 is an anti-PD-L1/TGF-β bispecific antibody fusion protein for treating advanced solid tumors and other indications. This product is also Boan Biotech's first bispecific antibody as an investigational new drug(IND) approved by the NMPA for clinical trials. The Phase I clinical trial approved is to evaluate the safety, tolerability, pharmacokinetic properties, and preliminary efficacy of BA1201 for the treatment of advanced solid tumors.

Different from the monoclonal antibodies against a single target, bispecific antibodies can bind to two antigens at the same time and regulate two signaling pathways related to cancer treatment, thus having unique advantages in cancer immunotherapy. BA1201 includes an anti-PD-L1 antibody infused with TGF-β Type II Receptor domain at its C terminal. BA1201 can not only inhibit PD-L1/PD-1 signaling pathway but also inhibit TGF-β/TGF-βRII signaling pathway, making it more potent than anti-PD-L1 monoclonal antibodies. This drug can eliminate immunosuppression and restore the immune system to target tumor cells for killing.

In the tumor microenvironment, programmed cell death ligand-1 (PD-L1) and transforming growth factor-β (TGF-β) are usually highly expressed. By binding to PD-1 on lymphocytes, PD-L1 inhibits the proliferation and activation of lymphocytes, induces their apoptosis, and then leads to the immune evasion of tumor cells. TGF-β not only drives tumorigenesis, but also serves as an important factor for immunosuppression. It mediates the drug resistance of tumor cells against the anti- PD-1/PD-L1therapy. Blocking the immunosuppressive signals induced through PD-L1 and TGF-β simultaneously can produce a synergy effect for cancer therapy.

Preclinical studies showed that BA1201 had a high affinity and significant antitumor activity in several mouse models. Compared with a reference product, BA1201 had a lower IC50 (50% inhibiting concentration) on PD-L1 positive cells, a good stability and a lower risk for cardiotoxicity.

Dr. Dou Changlin, President of R&D and COO of Boan Biotech, said: "Developing a bispecific antibody is more complex and involves a higher technical barrier compared with developing a conventional monoclonal antibody. Boan Biotech has multiple years of expertise and the ability to innovate efficiently and collaboratively. We believe this will help us accelerate the development of BA1201 and expand our portfolio with more valuable products."