LRK-4189 / Larkspur Biosci - LARVOL DELTA

Larkspur Biosciences Begins Dosing in Clinical Study of LRK-4189, a First-in-Class Targeted Protein Degrader (GlobeNewswire) - "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....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."

Trial status • Colorectal Cancer

LRK-4189, a first-in-class degrader of the lipid kinase PIP4K2C for the treatment of Microsatellite Stable (MSS) Colorectal Carcinoma (SITC 2025) - "PIP4K2C regulates local pools of PI(4,5)P2 through a catalytic-independent mechanism and is co-opted by cancer cells to increase their fitness by evading immune surveillance and adapting to stress.Methods Achieving potent targeting of PIP4K2C while sparing other family members or other lipid kinases has so far precluded the exploration of its potential as a therapeutic target.Results LRK-4189-mediated degradation of PIP4K2C leads to intrinsic cell death and activates type-1 immunity, triggering immune-mediated tumor killing in otherwise immune-inert MSS CRC cells. Subsequently, tumors are more susceptible to immune cell killing by NK cells and phagocytosis by dendritic cellsConclusions Collectively, our results show that PIP4K2C is a novel cancer fitness target at the critical convergence of tumor-intrinsic and tumor-immune pathways, and which can be specifically and effectively targeted in vivo using a bifunctional degrader.LRK-4189 is currently in IND-enabling studies..."

Colorectal Cancer • Oncology • Solid Tumor

Larkspur Biosciences Announces Discovery of LRK-4189, a First-in-Class Degrader of the Lipid Kinase PIP4K2C, for the Treatment of Microsatellite Stable (MSS) Colorectal Cancer at the ACS Fall 2025 Meeting (GlobeNewswire) - "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....LRK-4189 has completed IND-enabling studies and expects to initiate a Phase 1 clinical trial in Q4 2025."

New P1 trial • Preclinical • Colorectal Cancer

Larkspur Biosciences to Present New Preclinical Research on Lead Development Program Candidate, a First-in-Class PIP4K2C Protein Degrader, at AACR 2024 (GlobeNewswire) - "Larkspur Biosciences...announced that it will present positive preclinical efficacy data for LRK-A, Larkspur’s novel, lead investigational therapy targeting the lipid kinase PIP4K2C, in primary human tumor samples and an in vivo model of colorectal cancer (CRC). The data will be featured in a poster presentation at the 115th Annual Meeting of the American Association for Cancer Research (AACR 2024)....LRK-A drives monotherapy anti-tumor activity, including complete tumor regressions, in CRC patient samples and an in vivo model. IND-enabling studies are under way..."

Preclinical • Colorectal Cancer