PVTX-405 / SK Bio - LARVOL DELTA

The selective IKZF2 molecular glue degrader, PVTX-405, counters Treg immune suppression,shows significant tumor growth delay as single agent and synergistic response with immune checkpoint therapies (ICTs) (AACR 2024) - "Further, in vivo treatment of PVTX-405 in combination with ICTs, anti-PD1 or anti-LAG3, significantly increased animal survival and led to durable tumor regressions compared to ICTs alone. Together, these results demonstrate a strong synergy between ICTs and Treg destabilization through pharmacological degradation of IKZF2 and represent a promising combination strategy for treatment of cancer."

Oncology • CRBN • GSPT1 • IKZF1 • IKZF2 • IL2

Discovery of a Novel Series of iso-Indolinone-Based Glutarimides as Highly Efficacious and Selective IKZF2 Molecular Glue Degraders. (PubMed, J Med Chem) - "We developed a novel series of iso-indolinone-based glutarimides, identifying compound 55 as a potent, selective IKZF2 degrader with >90% Dmax in Jurkat cells, outperforming benchmarks DKY709 and PVTX-405. PK/PD studies confirmed profound, persistent IKZF2 degradation in mouse spleen and thymus after a single oral dose. As a promising early-stage tool, 55 provides a foundation for further preclinical evaluation in cancer immunotherapy."

Journal • Oncology • Targeted Protein Degradation • IKZF2

Development of PVTX-405 as a potent and highly selective molecular glue degrader of IKZF2 for cancer immunotherapy. (PubMed, Nat Commun) - "PVTX-405 in combination with anti-PD1 or anti-LAG3 significantly increases animal survival compared to anti-PD1 or anti-LAG3 alone. Together, these results demonstrate that PVTX-405 is a promising IKZF2 degrader for clinical development for the treatment of human cancers."

Journal • Oncology • Targeted Protein Degradation • CRBN • IKZF2 • IL2

Proteovant Therapeutics to Present Preclinical Data from Estrogen Receptor and IKZF2 Protein Degrader Programs (GlobeNewswire) - "Proteovant Therapeutics...announced it will present data on PVTX-321, an estrogen receptor degrader, at the Protein Degradation & Targeting Undruggables Congress USA, March 15-16 in Boston and on PVTX-405, an IKZF2 molecular glue, at the Targeted Protein Degradation Europe Conference, March 28-30 in London....'PVTX-321, our degrader targeting the estrogen receptor, is highly potent and demonstrates impressive, dose dependent tumor growth inhibition and shrinkage in preclinical models. In addition, PVTX-405 has best-in-class potential with robust IKZF2 degradation in vivo'."

Preclinical • Oncology