SIL204 treatment may help immune system attack KRAS-driven tumors, research finds - exclusive

Israeli company Silexion Therapeutics Corp. is developing a treatment called SIL204, which preclinical findings suggest may enhance the immune system's ability to attack KRAS-driven cancers. The research, released Wednesday, indicates SIL204 could combat three key ways tumors evade immune detection: increasing cancer cell visibility, restoring immune system-induced cell death, and diminishing immune evasion through reduced checkpoint molecules.

The treatment works by using small interfering RNA (siRNA) molecules to suppress the expression of mutated KRAS genes, a primary driver of tumor growth in certain cancers. KRAS mutations are prevalent, found in approximately 90% of pancreatic cancers and 30-35% of lung adenocarcinomas.

Studies on human cancer cell lines representing various KRAS mutations in pancreatic and lung cancers showed that SIL204 significantly increased the expression of FAS, an immune "death receptor," and notably reduced HLA-G, an immune checkpoint molecule. "These new findings meaningfully extend and reinforce the immuno-oncology profile of SIL204 that we first reported in May," said Ilan Hadar, Chairman and CEO of Silexion. "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."

This development comes as the oncology field investigates combining KRAS-directed therapies with checkpoint inhibitors. Silexion initiated its first clinical trial at Tel Aviv Sourasky Medical Center and advanced SIL204 into Phase 2/3 clinical evaluation at the end of July. The trial initially targets pancreatic cancer patients and is expected to expand to medical centers in Israel, Germany, and other countries.

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These new findings meaningfully extend and reinforce the immuno-oncology profile of SIL204 that we first reported in May. 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.