Synonyms: AGEN-1423 | AGEN1423 | GS-1423

Compound class: Antibody

Comment: Dalutrafusp alfa is a bispecific antibody-fusion protein that was designed as a checkpoint modulator for immuno-oncology. It was invented by Agenus (as AGEN-1423), and has been licensed to Gilead for clinical development (as GS-1423). The antibody portion of dalutrafusp targets the adenosine degrading enzyme ecto-5'-nucleotidase (NT5E/CD73; produces an immunosuppressive effect in the tumour micoenvironment), and this is fused via a peptidyl linker to the extracellular domain of transforming growth factor beta receptor 2 (TGFBR2) which acts as a molecular trap for both TGFβ1 and TGFβ3. NT5E and TGFβ are two significant resistance pathways that allow tumours to escape immune surveillance.
In the absence of a peer reviewed disclosure, analysis of patent documents suggests that dalutrafusp alfa may be closely related to the anti-CD73-TGF trap fusion protein BA037 that is claimed in Agenus' patent WO2019173692A2 [1]. The CDRs in the sequences of the anti-NT5E/CD73 mAb region from the dalutrafusp alfa INN document match SEQ IDs presented in the patent.