Undisclosed KEAP1- and VHL-recruiting PROTACs / SEED Therapeutics - LARVOL DELTA

SEED Therapeutics Highlights Breakthrough Advances in Targeted Protein Degradation at AACR 2025 (GlobeNewswire) - "At AACR, SEED reported the following findings: ST-00937 degrades RBM39 to undetectable levels in A673 Ewing sarcoma cells, both in vitro and in vivo; Treatment with ST-00937 leads to complete elimination of established A673 tumors within two weeks; Mechanistic studies demonstrate that ST-00937 impairs homologous recombination repair pathways in A673 cells... SEED expects to file an Investigational New Drug (IND) application for its next-generation RBM39 degrader, derived from ST-00937, in mid-2025...The second presentation at AACR highlighted a novel bifunctional degrader strategy that combines two PROTACs using two E3s targeting KRAS G12D...Key findings presented include: VHL-based PROTACs targeting KRAS G12D display the classic hook effect at high concentrations; KEAP1-based PROTACs synergize with VHL-based PROTACs to enhance KRAS G12D degradation and promote apoptosis in pancreatic cancer models....Synergistic effects were also observed..."

IND • Preclinical • Ewing Sarcoma • Pancreatic Cancer • Sarcoma

SEED Therapeutics Reports Breakthroughs for Two Targeted Protein Degradation Projects at AACR Annual Meeting in Chicago (GlobeNewswire) - "Two PROTAC synergy using two E3 ligases for achieving levels of degradation of KRAS G12D not achieved with single PROTACs, will be presented by the lab of Luca Busino, PhD, from the University of Pennsylvania, on April 27th....SEED’s first IND candidate project targeting RBM39: Ewing sarcoma will be presented as an important target on April 30th."

Preclinical • Ewing Sarcoma