On August 4, 2026 Silexion Therapeutics Corp. (NASDAQ: SLXN) ("Silexion" or the "Company"), a clinical-stage biotechnology company pioneering RNA interference (RNAi) therapies for KRAS-driven cancers, reported additional positive preclinical findings from its ongoing translational immuno-oncology program evaluating SIL204 in human KRAS-mutant cancer cells. The new findings further expand SIL204’s therapeutic profile by demonstrating a coordinated immune-sensitizing effect on tumor cells, reinforcing the scientific rationale for combining SIL204 with anti-PD-(L)1 checkpoint inhibitor therapies. In newly reported studies performed across three human cancer cell lines representing three different KRAS mutations, SIL204 treatment produced statistically significant increases in expression of FAS, a well-established immune "death receptor," and statistically significant reductions in expression of HLA-G, an immune checkpoint that tumors use to evade immune surveillance. The findings, generated in human pancreatic (KRAS G12D) and non-small cell lung cancer (NSCLC; KRAS G12V and G12C) cell lines, build on the Company’s previously reported MHC-I upregulation data announced in May 2026, and further support SIL204’s potential to act as a multi-mechanism immune sensitizer in KRAS-driven tumors.
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"These new findings meaningfully extend and reinforce the immuno-oncology profile of SIL204 that we first reported in May," said Ilan Hadar, Chairman and Chief Executive Officer of Silexion Therapeutics. "In one integrated dataset, we are now seeing that SIL204 modulates three of the most important mechanisms by which KRAS-driven tumors evade the immune system – upregulating antigen presentation via MHC-I, upregulating FAS to restore sensitivity to immune-mediated cell death, and downregulating the HLA-G immune checkpoint to remove a key inhibitory signal to immune cells. SIL204 is producing this coordinated immune-sensitizing effect across multiple KRAS mutations and both of the largest KRAS-driven tumor types. We believe this profile supports the rationale for further evaluation of SIL204 in combination with anti-PD-(L)1 checkpoint inhibitor therapies, particularly in indications like pancreatic cancer where these agents have historically shown limited single-agent efficacy."
FAS (also known as CD95) is a cell surface death receptor whose engagement by Fas ligand (FasL) – which is expressed on activated CD8+ T cells and natural killer (NK) cells – triggers programmed cell death of the target cell. Cancer cells, and KRAS-driven tumors in particular, commonly downregulate FAS to evade immune-mediated killing. Recent research published in Developmental Cell (Cell Press) has demonstrated that elimination of oncogenic KRAS in genetic mouse models of pancreatic ductal adenocarcinoma restores FAS expression and enables FasL-expressing CD8+ T cells to eradicate KRAS-driven tumors.¹ In the newly reported Silexion study, SIL204 treatment produced statistically significant, dose-dependent increases in FAS expression at 72 hours in human KRAS G12D-mutant pancreatic cancer cells (PK59; up to approximately 2-fold, P<0.0001 vs. control) and in KRAS G12V-mutant NSCLC cells (CORL23; P<0.05 vs. control).
HLA-G is a non-classical HLA class I molecule that functions as a potent immune checkpoint. When expressed on tumor cells, HLA-G binds inhibitory receptors – including ILT-2 (LILRB1), ILT-4 (LILRB2), and KIR2DL4 – on CD8+ T cells, NK cells, and myeloid immune cells, suppressing their anti-tumor activity and enabling immune escape.² HLA-G is a recognized and increasingly prominent drug target in oncology, with multiple HLA-G-directed programs currently in clinical development in advanced solid tumors. In the newly reported study, SIL204 treatment produced statistically significant, dose-dependent reductions in HLA-G expression in human KRAS G12C-mutant NSCLC cells (NCI-H358; P<0.001 at 24 hours and P<0.01 at 72 hours vs. control at the 200 nM dose), with additional reductions observed in KRAS G12D-mutant pancreatic and KRAS G12V-mutant NSCLC cells.
Taken together with the Company’s previously reported May 2026 findings demonstrating statistically significant upregulation of MHC-I (HLA-ABC) in KRAS G12R-mutant pancreatic cancer cells, these new data support a coordinated immune-sensitization signature across three key immune pathways. The immune-modulatory effects have now been observed across four distinct KRAS mutations (G12D, G12V, G12C, and G12R) in both pancreatic and non-small cell lung cancer models, reinforcing the potential applicability of SIL204’s mechanism across the largest KRAS-driven cancer patient populations.
The findings arrive at a moment when the oncology field is actively exploring combinations of KRAS-directed therapies with immune checkpoint inhibitors, with recent academic and industry work demonstrating that combining KRAS inhibition with anti-PD-1 or anti-PD-L1 agents can produce sustained tumor regression and reprogramming of the tumor microenvironment in KRAS-driven cancers.³ Pancreatic ductal adenocarcinoma and KRAS-mutant NSCLC together represent the largest KRAS-driven patient populations, with KRAS mutations present in approximately 90% of pancreatic cancers and 30–35% of lung adenocarcinomas. Immune checkpoint inhibitors have shown limited single-agent efficacy in pancreatic cancer and variable response rates in KRAS-mutant NSCLC, driving substantial scientific and commercial interest in strategies capable of converting "immunologically cold" tumor phenotypes into more immunotherapy-responsive tumors. The Company believes these findings provide additional translational support for SIL204’s ongoing Phase 2/3 clinical development.
(Press release, Silexion Therapeutics, AUG 4, 2026, View Source [SID1234669681])