molecules of the month

A Treg-modulating IKZF2 (Helios) glue degrader for cancer immunotherapy. Tumors can evade the immune system through the recruitment of regulatory T cells (Treg) which limit the activation and expansion of effector T cells (Teff). IKZF2 (Helios) is an Ikaros transcription factor family member that is expressed in a majority of Treg cells. NVP-DKY709 is a first-in-class selective molecular glue degrader of IKZF2 that makes Treg cells less immunosuppressive and Teff cells more active in vitro, while completely sparing the traditional pomalidomide targets IKZF1/3 from degradation. It has demonstrated significant and sustained IKZF2 degradation in a Ph. I clinical trial (NCT03891953, not recruiting) and was intended to be studied in combination with PD-1 antibody, spartalizumab in NSCLC or melanoma patients who…