Silexion Therapeutics Corp. (NASDAQ: SLXN) (“Silexion” or the “Company”), a clinical-stage biotech developing RNA interference (RNAi) therapies for KRAS-driven cancers, announced new preclinical results demonstrating the synergistic efficacy of its proprietary second-generation siRNA candidate, SIL-204, in combination with components of first-line chemotherapy for pancreatic cancer. The additional preclinical data show that SIL-204 exhibits significant synergistic activity with 5-fluorouracil and irinotecan—two main components commonly used in pancreatic cancer treatments—when tested in human pancreatic tumor cell lines harboring KRAS G12D mutations, the most common mutation in pancreatic cancer. Moreover, synergistic activity was also observed with the chemotherapeutic agent gemcitabine.

This promising synergistic activity was observed after the confluence of these tumor cell lines, reflecting how SIL-204 may enhance the effects of 5-fluorouracil and irinotecan when used together, as well as that of gemcitabine. For example, in preclinical models, the combination of 5-fluorouracil and irinotecan with SIL-204 led to a significant reduction in cancer cell confluence after about three days compared to treatment with the chemotherapy agents alone (p < 0.0005), further supporting the synergistic potential of SIL-204 in enhancing standard chemotherapy treatments. This comes on top of previous recent announcements from Silexion regarding pre-clinical findings from the ongoing development of SIL-204, in line with earlier successes with the company’s first-generation product, LODER™ (siG12DLoder), which showed a significant improvement in overall survival in the siRNA plus chemotherapy arm compared to chemotherapy alone in Phase 2 trials.

“These new findings, combined with the substantial milestones we have recently reported in developing SIL-204, suggest that Silexion’s approach could potentially revolutionize the treatment landscape not only for pancreatic cancer but also for a wide range of KRAS-mutated cancers, which remain some of the most difficult to treat. The synergy demonstrated between SIL-204 and first-line chemotherapies underscores its potential to enhance existing treatment regimens and address significant unmet needs across multiple oncology indications,” said Ilan Hadar, Chairman and CEO of Silexion.

As previously reported, Silexion is gearing up for the clinical development of SIL-204, Planning to initiate toxicology studies with SIL-204 within the upcoming months and to advance SIL-204 into Phase 2/3 clinical trials in the first half of 2026, focusing initially on locally advanced pancreatic cancer (LAPC) which has a notoriously high mortality rate. In parallel, the company plans to initiate preclinical studies for SIL-204, in colorectal cancer models.