ERAP2 inhibitor / GreyWolf Therapeutics - LARVOL DELTA

Modulation of antigen presentation by first-in-class ERAP1 and ERAP2 inhibitors for the treatment of cancer and autoimmunity (IMMUNOLOGY 2024) - "Importantly, we apply a state-of-the-art immunopeptidomics pipeline to define the qualitative and quantitative effects of these inhibitors. Our data demonstrate that ERAP1 and ERAP2 have overlapping and distinct effects on the antigen repertoire, consistent with their respective substrate specificities."

Immunology • Oncology

Development of first-in-class ERAP2 inhibitors to modulate the cancer immunopeptidome (SITC 2023) - "We have previously described the preclinical development of the First-in-Class (FIC) ERAP1 inhibitor, GRWD5769, which has now entered Phase I clinical trials. Conclusions ERAP2 is a genetically-validated target for human cancer and member of an emerging category of therapeutic targets in the antigen presentation pathway that can alter the visibility of cancer through generation of novel cancer antigens. Current efforts are focused on optimizing our lead FIC ERAP2 inhibitors and validating ERAP2 inhibition in human and mouse cancer models."

IO biomarker • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A small molecule approach to drive novel neoantigen generation: First-in-class inhibitors of ERAP1 generate novel neoantigens driving anti-tumor effects (AACR 2022) - "Grey Wolf are developing inhibitors of endoplasmic reticulum aminopeptidases (ERAP1 and ERAP2) to generate novel neoantigens. Importantly, ERAP1 inhibitors are well tolerated in mouse, rat, and non-human primates, which aligns with the observations that increases in T cell effects are tumor specific and not observed in peripheral tissue. Our investigation of the effects of ERAP1 inhibitors in mouse tumor models and ex vivo primary human T cell co-cultures have provided proof of mechanism and proof of principle biomarkers that will be used to explore the effects of GRWD5769 during Phase 1 clinical development in the second half of 2022."

IO biomarker • Tumor-specific neoantigens • Oncology • TMB