Silexion Therapeutics Corp. announced positive preclinical findings regarding its lead RNA interference (RNAi) candidate, SIL204, on September 28, 2026. The company, focused on oncology treatments for KRAS-driven cancers, released a press release detailing results from an ongoing translational study. The study evaluated the cellular uptake and gene-silencing mechanism of SIL204, which is currently in a Phase 2/3 clinical program for locally advanced pancreatic cancer.
The findings demonstrate that SIL204 effectively utilizes native serum lipids to achieve intracellular delivery. In a carrier-free, non-transfection assay using human KRAS-driven cancer cells, SIL204 exhibited robust, dose-dependent gene silencing in the presence of standard physiological serum lipids. Conversely, depletion of serum lipids resulted in a statistically significant reduction in gene-knockdown efficiency (P < 0.001). The company noted that adding exogenous human low-density lipoprotein (LDL) did not alter the gene-silencing potency compared to complete serum alone, indicating that endogenous lipid levels are sufficient for cellular entry.
Silexion highlighted that the LDL receptor is upregulated in cancer cells compared to healthy cells, which the company views as an endogenous targeted delivery mechanism. The company stated that these results provide mechanistic support for its broader clinical development strategy, specifically regarding the potential for systemic administration to address micro-metastases. The company is currently conducting additional preclinical evaluations, including in vivo pharmacokinetic and tissue biodistribution studies.
In addition to the preclinical findings, Silexion reported that it is actively initiating clinical trial sites, including at Tel Aviv Sourasky Medical Center, and pursuing regulatory clearances in Germany.
