AETX-R302 / Aethon Therap - LARVOL DELTA

Deciphering the molecular basis for pan-HLA recognition of divarasib-modified pMHCs by newly discovered hit-to-lead antibody AETX-R302 (AACR 2025) - "The potential of exploiting synthetic neoantigens is well demonstrated by antibody AETX-R114, which recognizes multiple hapten-peptides (sotorasib-conjugated KRASG12C peptides) presented by different HLAs. Collectively, the cryo-EM structures explain AETX-R302's unprecedented A2/A3 supertype cross-reactivity and its high specificity and affinity. This information will be exploited to develop TCEs that engage tumor-specific synthetic neoantigen targets with pan-HLA recognition."

Oncology • KRAS

Engineered antibodies that stabilize drug-modified KRASG12C neoantigens enable selective and potent cross-HLA immunotherapy. (PubMed, Nat Commun) - "To address challenges by their low copy number, we develop AETX-R114, a T cell engaging bispecific antibody with picomolar affinity for MHC-restricted sotorasib-modified KRASG12C peptides presented by three HLA-A3 supertype alleles...To broaden the therapeutic potential of creating and targeting synthetic neoantigens, we further develop AETX-R302, which recognizes divarasib-modified KRASG12C peptides presented on alleles from the HLA-A2 and A3 supertypes. Cryo-EM structure determination reveals the molecular basis for breaking HLA supertype restriction. Collectively, our study illustrates how engineered antibodies can transform synthetic neoantigens into actionable cancer immunotherapy targets."

Journal • Oncology • KRAS