, which is a first-of-its-kind degrader targeting the lipid kinase PIP4K2C, has been discovered and announced by Larkspur Biosciences.Cancer cells possess unique adaptations to help them survive and evade both the body’s natural defense systems and external treatments. One key protein involved in this process is PIP4K2C, a lipid kinase that helps cancer cells adapt to stress and escape immune surveillance. While genetic research has long identified PIP4K2C as a crucial player in cancer cell survival, its very low enzymatic activity has made it a difficult target for traditional drug development. Larkspur Biosciences has successfully overcome this challenge with LRK-4189, a novel degrader that effectively dismantles this protein rather than simply inhibiting it. According to Catherine Sabatos-Peyton, PhD, the CEO of Larkspur Biosciences, this new approach has the potential to overcome the limitations of earlier therapies by reducing cancer cell fitness, triggering a natural process of cell death, and engaging the immune system to clear out any remaining tumor cells.

Colorectal cancer is a significant health concern, with approximately 150,000 new cases diagnosed annually in the United States. A large majority of these cases, about 85%, are classified as MSS CRC, a form of the disease that is particularly difficult to treat. LRK-4189 shows promise as a new treatment for this patient population.

LRK-4189 is an orally administered drug with high selectivity and potency. By degrading PIP4K2C, it induces intrinsic cancer cell death and activates interferon signaling, which triggers multiple killing mechanisms in difficult-to-treat MSS CRC cells. In preclinical studies, LRK-4189 has demonstrated significant dose-dependent efficacy on its own and has shown synergy with standard-of-care chemotherapy in animal models. The drug also performed favorably in patient-derived tumor samples, showing a response rate of 50% in primary human MSS CRC samples, which is better than the 35% response rate seen with the benchmark drug cetuximab in the same testing platform. With these promising results, LRK-4189 has successfully completed its necessary preclinical studies, and Larkspur expects to begin a Phase 1 clinical trial later this year.

Larkspur Biosciences is a company at the forefront of a new approach to cancer therapy, focusing on strategies that weaken cancer cell fitness. The company uses a proprietary bioinformatics platform called LarkX, which combines machine learning with tumor genetics to identify and target these specific survival pathways. The company was founded by a team of leading scientists from esteemed institutions such as the Dana-Farber Cancer Institute, Harvard Medical School, Brigham and Women’s Hospital, and Stanford University.