Silexion Therapeutics Reports New Preclinical Data Supporting SIL204 Combination With Immunotherapy In KRAS-Driven Cancers

Silexion Therapeutics Corp., a clinical-stage biotechnology company developing RNA interference (RNAi) therapies for KRAS-driven cancers, has announced additional positive preclinical findings for its investigational therapy, SIL204. The latest results from the company's translational immuno-oncology program show that SIL204 may help make KRAS-mutant cancer cells more responsive to the body's immune system, further supporting its potential use in combination with anti-PD-(L)1 immune checkpoint inhibitors.

The newly reported studies were conducted in three human cancer cell lines representing different KRAS mutations, including pancreatic cancer with the KRAS G12D mutation and non-small cell lung cancer (NSCLC) with KRAS G12V and G12C mutations. 

Researchers found that SIL204 significantly increased the expression of FAS, a receptor that helps immune cells trigger cancer cell death, while significantly reducing the expression of HLA-G, an immune checkpoint protein that tumors use to escape immune detection. 

These findings build on previously reported data from May 2026 showing that SIL204 also increased MHC-I expression, another important factor that improves the immune system's ability to recognize cancer cells.

Chairman and Chief Executive Officer Ilan Hadar said the new data strengthen the immuno-oncology profile of SIL204 by demonstrating its ability to influence three major pathways that KRAS-driven tumors use to avoid immune attack. According to the company, SIL204 enhances antigen presentation through MHC-I, restores cancer cell sensitivity to immune-mediated destruction by increasing FAS expression, and reduces immune suppression by lowering HLA-G levels. 

These coordinated effects were observed across multiple KRAS mutations and in two of the most common KRAS-driven cancers, supporting further evaluation of SIL204 alongside anti-PD-(L)1 checkpoint inhibitor therapies, particularly for pancreatic cancer where immunotherapies have historically shown limited success as standalone treatments.

The company explained that FAS, also known as CD95, is a cell surface receptor that enables activated immune cells, including CD8+ T cells and natural killer (NK) cells, to eliminate cancer cells. Many KRAS-driven tumors reduce FAS expression to avoid immune destruction. In the latest study, SIL204 produced statistically significant and dose-dependent increases in FAS expression in KRAS G12D-mutant pancreatic cancer cells and KRAS G12V-mutant NSCLC cells, suggesting the therapy may help restore the immune system's ability to kill tumor cells.

Researchers also observed statistically significant reductions in HLA-G expression following SIL204 treatment. HLA-G is an immune checkpoint molecule that suppresses the activity of T cells, natural killer cells, and other immune cells, allowing tumors to evade immune surveillance. The strongest reductions were seen in KRAS G12C-mutant NSCLC cells, with additional decreases observed in pancreatic and lung cancer models carrying other KRAS mutations. Since HLA-G has emerged as an important target for cancer immunotherapy, lowering its expression may improve the effectiveness of immune-based treatments.

When combined with the company's previously reported findings showing increased MHC-I expression, the new results demonstrate that SIL204 influences three critical immune pathways across four different KRAS mutations—G12D, G12V, G12C, and G12R—in both pancreatic and non-small cell lung cancer models. 

Silexion believes these findings strengthen the scientific rationale for its ongoing Phase 2/3 clinical development of SIL204. The results also come as researchers increasingly explore combinations of KRAS-targeted therapies with immune checkpoint inhibitors, particularly in pancreatic cancer and KRAS-mutant NSCLC, where there remains a significant need for treatments that can improve responses to immunotherapy.