Cancer fitness genes drive pathways that create a survival advantage for malignant cells beyond proliferative mechanisms. These targets are conditionally essential in stress conditions. Larkspur’s degraders target these genes to make cancer cells more susceptible to competition, physiological cell death, and killing mechanisms.
LRK-4189 is a first-in-class targeted protein degrader of PIP4K2C, a lipid kinase associated with poor outcomes in multiple cancers, including microsatellite stable (MSS) colorectal cancer (CRC). PIP4K2C is hijacked by cancer cells to increase their fitness and is conditionally essential in cancer-driven stress.
Why targeted protein degradation?
Larkspur discovered that effective targeting of PIP4K2C requires degradation, rather than conventional inhibition.
By rewiring tumor-intrinsic pathways, LRK-4189 triggers cell death through loss of intrinsic stress adaptions and subsequent metabolic failure.