– First-in-human, Phase 1 Study of LRK-4189 to Begin in the Fourth Quarter
Cambridge, MA, August 20, 2025 – Larkspur Biosciences, a company pioneering a new wave in cancer therapy that destroys tumors by targeting cancer cell fitness, today announced the discovery of LRK-4189, a first-in-class degrader of the lipid kinase PIP4K2C for the treatment of microsatellite stable (MSS) colorectal cancer (CRC) and other solid tumors. The announcement was made at a presentation Larkspur was invited to give at the prestigious MEDI First Time Disclosures: Breakthroughs on New Medicines session at ACS Fall 2025, a meeting of the American Chemical Society in Washington, DC.
Cancer cells maintain their fitness by developing survival adaptations that foster escape from intrinsic and extrinsic mechanisms of cell death in conditions of stress. Phosphatidylinositol 5-phosphate 4-kinase, type II, gamma (PIP4K2C) is a lipid kinase associated with poor outcomes in a range of cancers including CRC and breast cancers. PIP4K2C is co-opted by cancer cells to increase their fitness by evading immune surveillance and adapting to stress.
“Genetic studies have long highlighted PIP4K2C as a key player in cancer stress adaptation, but its extremely low kinase activity made it resistant to conventional inhibition approaches,” said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. “With our novel degrader, LRK-4189, we’ve finally unlocked this critical pathway. By reducing cancer cell fitness, triggering intrinsic apoptosis, and engaging the immune system to clear residual tumor cells, LRK-4189 has the potential to overcome the limitations of earlier therapies. We’re excited to advance this promising therapy to the clinic later this year.”
According to the American Cancer Society, in the United States, approximately 150,000 cases of CRC are diagnosed annually, with MSS CRC accounting for about 85% of all CRC cases.
About LRK-4189
- LRK-4189 is an orally bioavailable, selective degrader of PIP4K2C with subnanomolar potency in primary human cells.
- LRK-4189-mediated degradation of PIP4K2C leads to intrinsic cancer cell death and activates interferon signaling, triggering multiple killing mechanisms in difficult-to-treat MSS CRC cells.
- In vivo, LRK-4189 demonstrates dose dependent PKPD with single agent efficacy in multiple models of CRC and synergy with first-line standard of care chemotherapy.
- In primary human CRC patient-derived spheroids, 50% of patient samples respond to LRK-4189 with a preferential response in MSS CRC, which compares favorably to benchmark cetuximab in the same platform (35%). Cetuximab may be either a first- or second-line treatment in people with RAS wild type CRC.
- LRK-4189 has completed IND-enabling studies and expects to initiate a Phase 1 clinical trial in Q4 2025.
About Larkspur Biosciences
Larkspur Biosciences is pioneering a new wave in cancer therapy that destroys tumors by targeting cancer cell fitness. Larkspur develops therapies that decrease cancer cell fitness and sensitizes the cells to intrinsic and immune-driven mechanisms of killing. The company is advancing first-in-class programs that target the adaptations cancer cells use to proliferate, invade tissue, and escape the immune system. LarkX, the company’s proprietary bioinformatics platform, couples machine learning with tumor genetics to discover cancer cell fitness pathways that originate in the tumor and enrich clinical strategies for potential responders to its therapies across multiple types of cancer. Larkspur’s founders include Lewis C. Cantley, PhD, professor of medicine at Dana-Farber Cancer Institute, professor of cell biology at Harvard Medical School; Vijay K. Kuchroo, DVM, PhD, professor of neurology at Harvard Medical School, senior scientist at Brigham and Women’s Hospital; and Nathanael Gray, PhD, professor of chemical and systems biology at Stanford University.
Visit us at larkspur.bio and follow us on LinkedIn and X.
Media Contact:
Dan Boyle
ScientPR
dan@scientpr.com