PVTX-405

PVTX-405 is a potent, highly selective, and orally bioavailable small molecule molecular glue degrader targeting IKZF2 (Helios), a transcription factor critical for regulatory T cell (Treg) function in the tumor microenvironment. By inducing the ubiquitination and proteasomal degradation of IKZF2 via recruitment to an E3 ligase complex, PVTX-405 disrupts Treg-mediated immunosuppression, thereby enhancing anti-tumor immune responses. Preclinical studies demonstrate that PVTX-405 robustly degrades IKZF2 with high selectivity (DC50 = 0.7 nM; Dmax = 91%), spares other Ikaros family proteins, increases IL-2 production, reduces Treg suppressive activity, and promotes effector T cell proliferation. In animal models of cancer—including both hematologic malignancies and solid tumors—once-daily oral administration of PVTX-405 significantly delays tumor growth and improves survival as monotherapy or in combination with immune checkpoint inhibitors such as anti-PD1 or anti-LAG3 antibodies. The drug is being developed for cancer immunotherapy by leveraging targeted protein degradation to address previously undruggable targets[2][3][4][5].