Researchers from Royal College of Surgeons in Ireland (RCSI) have created a new orthotopic preclinical model of glioblastoma (GBM), designed to recapitulate patient response to standard-of-care and targeted treatments.

Researchers from Adcentrx Therapeutics Inc. recently reported preclinical data for the Nectin-4-targeting antibody-drug conjugate (ADC) ADRX-0706, currently in phase I development for the treatment of solid tumors (NCT06036121).

The existence of two approved therapies, Lumakras (sotorasib, Amgen Inc.) and Karzati (adagrasib, Mirati Therapeutics Inc.), has been a triumphant success against KRAS, a protein that was once considered undruggable. KRAS is the most frequently mutated oncogene in solid tumors. KRAS driver mutations are found in about 30% of non-small-cell lung cancers (NSCLC), about half of colorectal cancers, and more than 90% of pancreatic cancers. Lumakras and Karzati both target the G12C mutation. Inhibitors that target other mutations, like G12D, are now making their way through preclinical and clinical development, while some companies are developing therapies that would target mutated KRAS more broadly, irrespective of the specific mutation that is activating the protein.

Newco Outrun Therapeutics Ltd. has raised $10 million in a seed round to develop small-molecule E3 ubiquitin ligase inhibitors that prevent programmed protein degradation. The lead program targeting an E3 ligase that tags a tumor suppressor protein for destruction will now advance to preclinical development.