Larkspur Biosciences Begins Dosing in Clinical Study of LRK-4189, a First-in-Class Targeted Protein Degrader

• LRK-4189, which targets PIP4K2C, a key cancer cell fitness target, is being developed for microsatellite stable (MSS) colorectal cancer (CRC) and other solid tumors
• Clinical study begins with healthy participants to establish early tolerability, pharmacokinetics, and pharmacodynamics

CAMBRIDGE, Mass., Dec. 03, 2025 (GLOBE NEWSWIRE) -- Larkspur Biosciences, a company pioneering a new wave in cancer therapy that destroys tumors by targeting cancer cell fitness, today announced that the first participant has been dosed in the Phase 1 clinical study of its lead candidate, LRK-4189, in healthy volunteers. LRK-4189 is a first-in-class targeted protein degrader of the lipid kinase PIP4K2C being developed as a potential treatment for microsatellite stable (MSS) colorectal cancer (CRC) and other solid tumors.

“Given the preclinical safety and measurable biomarkers of LRK-4189 activity, starting in healthy volunteers is the most direct way to understand its pharmacology and define a biologically meaningful dose,” said Catherine Sabatos-Peyton, Ph.D., CEO of Larkspur Biosciences. “This approach positions us to begin patient studies at dose levels that matter on day one. We look forward to sharing study progress next year.”

“While it’s been established that PIP4K2C is broadly expressed in many hard-to-treat cancers, including colorectal cancer, this pathway has been elusive to engage with therapeutically until now,” said Antoni Ribas, M.D., Ph.D., professor of medicine, surgery, and molecular medical pharmacology at the University of California Los Angeles (UCLA), Past President of the American Association for Cancer Research (AACR), and Larkspur advisor. “Larkspur’s data on LRK-4189 in preclinical models of cancer are compelling, and we’re looking forward to seeing the impact of this potential new approach on treating advanced solid tumors.”

According to the American Cancer Society, in the U.S., approximately 150,000 cases of CRC are diagnosed annually, with MSS CRC accounting for about 85% of all CRC cases.

The Phase 1 study is a single-ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of LRK-4189 in healthy volunteers. The United Kingdom-based study expects to enroll approximately 40 participants. The clinical program and recruitment of healthy volunteers will be handled by Quotient Sciences.

About Cancer Cell Fitness and PIP4K2C

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. 

About LRK-4189

LRK-4189 is an oral, first-in-class targeted protein degrader of the lipid kinase PIP4K2C. LRK-4189-mediated degradation of PIP4K2C leads to intrinsic cancer cell death, triggering multiple killing mechanisms in difficult-to-treat cancer cells.

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 sensitize the cells to intrinsic and extrinsic 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.

Media Contact:
Dan Boyle

ScientPR
dan@scientpr.com