Silexion Therapeutics Corp., a clinical-stage biotechnology company pioneering RNA interference (RNAi) therapies for KRAS-driven cancers, today announced positive data from orthotopic pancreatic cancer models demonstrating that subcutaneously administered SIL204 effectively reduces both primary tumor growth and metastatic spread.

These findings represent a significant advancement over previously reported data by providing further validation of SIL204's efficacy in the more clinically relevant orthotopic setting, where human pancreatic tumor cells are implanted directly into the pancreas to better mimic human disease progression, including, for the first time, in metastasis patterns.

Key New Findings

Initial validation using orthotopic models: SIL204 administered subcutaneously (systemically) showed significant efficacy in orthotopic xenograft models where tumors grow in their native pancreatic environment, representing a more clinically relevant setting than our previous subcutaneous xenograft models.

Cell line-specific efficacy profiles: SIL204 showed robust activity across multiple pancreatic cancer cell lines with different KRAS mutation profiles:
In AsPC-1 (harboring KRAS G12D mutation): ~70% reduction in overall bioluminescence (an indication of tumor cell number) as compared to the control group, by day 28.

In Panc-1 (harbouring KRAS G12D mutation): Bioluminescence or tumor cell numbers decreased dramatically in a dose-dependent manner, with the highest-dose group showing the most significant effect. Bioluminescence in the control group increased by approximately more than 100% while in the SIL204 treated group it decreased by 12% compared to baseline, a substantial reduction by day 14 compared with the control group (P-value < 0.05), demonstrating the significant therapeutic impact of SIL204.

In BxPC-3 (additional KRAS wild-type model): ~80% reduction in overall  bioluminescence, as compared to the control group, by day 28.
Metastasis reduction demonstrated for the first time: SIL204 treatment significantly reduced metastatic spread to secondary organs; substantially lowering metastatic burden across the liver, intestine, spleen and stomach in the two models checked for the various organs, Panc-1 and BxPC-3 models.
Initial validation for systemic delivery efficacy: Subcutaneous administration of SIL204 proved effective in reaching and treating pancreatic tumors and their metastases, confirming systemic delivery as a viable administration route.

These orthotopic model results represent a pivotal advancement in our development program, said Mitchell Shirvan, Ph.D., CSO of Silexion. "While our previous data showed SIL204's ability to reduce tumor growth in standard models, these new findings provide initial validation of its potential effectiveness in a much more clinically relevant setting. Particularly exciting is the demonstration that SIL204 can significantly reduce metastatic spread when administered subcutaneously, suggesting potential for treating both primary and metastatic disease with a minimally-invasive delivery method.

Based on these encouraging results, Silexion is actively exploring an expanded development plan for SIL204 using the systemic administration approach. The Company is finalizing an updated development strategy that leverages these new findings and expects to provide more detailed information in the coming weeks, as previously indicated in recent announcements.

These results mark the first time we've demonstrated SIL204's ability to address metastatic disease through subcutaneous administration, badded Ilan Hadar, Chairman and CEO of Silexion. "The ability to deliver our therapy systemically and still effectively target both primary pancreatic tumors and their metastases represents a significant potential advantage for treating this devastating disease.

Source: https://www.globenewswire.com/news-release/2025/03/05/3037405/0/en/Silexion-Therapeutics-Reports-Groundbreaking-Positive-Initial-Data-from-Systemic-Administration-of-SIL204-in-Orthotopic-Pancreatic-Cancer-Models.html