On November 24^th 2020, the IND application submitted for PD-L1/VEGF bispecific antibody HB0025 by Huabo Biopharm, a subsidiary of Zhejiang Huahai Pharmaceutical, was accepted by NMPA.

Huahai Pharmaceutical has declared four new antibody drugs, including VEGFR fusion protein, IL-17A antibody, 4-1BB antibody, and PD-L1/VEGF bispecific antibody.

Huabo Biopharma’s first macromolecular drug is a VEGFR fusion protein drug, which is a biosimilar to Regeneron’s Aflibercept and Kanghong Pharmaceutical’s Conbercept. Using receptor as ligand Trap is a common fusion protein drug design strategy, such as aflibercept for VEGF trap and TGFβRII for TGFβ trap. HB002 is less fused with VEGFR2 D3 based on aflibercept.

HB0025 is VEGFR1 domain 2 (that is, the structure of HB002) fused to the C-terminus of the heavy chain of the PD-L1 antibody (900388).

ImmuneOnco Biopharma and GeneScience Pharmaceuticals have also developed PD-L1/VEGFR fusion protein. IMM2510 from ImmuneOnco is similar in structure with HB0025, VEGFR1 D2 is fused to the N-terminus of the heavy chain of the PD-L1 antibody.

BT001 from GeneScience Pharmaceuticals is aflibercept (VEGFR1 D2-VEGFR2 D3) fused to the C-terminus of the heavy chain of the PD-L1 antibody.

Conclusion

In February 2020, PD-L1antibody form Roche Tecentriq combined with VEGF antibody Avastin has achieved breakthrough in the treatment of liver cancer, which is significantly better than sorafenib, with 42% reduction in risk of death. The combination or bispecific antibody of PD-(L)1 and VEGF has become a competing trend for domestic pharmaceutical companies. Hengrui pharmaceutical, Junshi Biosciences, BeiGene, Innovent are actively developing the combination therapy of PD-1 and VEGF antibody biosimilars. At the ESMO Asia Annual Conference, Innovent verbally reported the progress of its combination therapy, compared with sorafenib, the first-line treatment of liver cancer reduces the risk of death by 43.1%, which is equivalent to Roche's data

In terms of bispecific antibodies, the PD-1/VEGF antibody AK112 of Akeso has made the furthest progress, Immuneonco and Huahai have just submitted IND application. In addition, Doer Biologics has developed a PD-L1/TGFβ/VEGF triantibody, Zelgen Biopharmaceuticals has developed PD-L1/VEGF/TBN-P triantibodym etc.