Synonyms: Ezeli® (China) | SHR-1701 | SHR1701

retlirafusp alfa is an approved drug

Compound class: Antibody

Comment: Retlirafusp alfa (SHR-1701) is a bifunctional fusion protein that comprises an anti-programmed death ligand 1 (PD-L1) monoclonal antibody fused to two copies of a N-terminally truncated extracellular domain (ECD) of human transforming growth factor beta receptor type 2 (TGFBR2). The TGFβR2 domain acts as a ligand trap for the receptor's endogenous ligand. Based on evidence that both the TGFβ pathway and the PD-PD-L1/PD-1 immune checkpoint are associated with tumour immune evasion, simultaneous targeting of these pathways was predicted to control tumour growth by restoring and enhancing anti-tumour immune responses [1,5,8,10]. This mechanism is also proposed to overcome tumour resistance to PD-1/PD-L1 inhibitors [2].

Peptide sequence alignments suggest that retlirafusp alfa is one of the claims in patent US11274142B2 [4]: the heavy and light chains are 100% identical to SEQ IDs 11 and 12, the truncated TGFβR2 ECD (amino acids 22-136) is identical to SEQ ID 14, and linker used matches the structure (G₄S)₄G that is used for the construct named "Fusion protein 10" [structure Ab-(G₄S)₄G-ECD(22-136)] in the patent. Unfortunately no binding affinity values for interactions with PD-L1 or TGFβ ligands are presented for this construct in the patent data tables or figures. Retlirafusp alfa is similar in structure and function to bintrafusp alfa (M7824), and indeed M7824 is used as a comparator in the patent discussed above.