Silexion Therapeutics announced positive preclinical data for SIL-204, its RNAi therapeutic candidate targeting KRAS-driven cancers. The data validates systemic administration of the drug, showing significant tumor reduction in orthotopic pancreatic cancer models. Further research will investigate SIL-204’s impact on metastasis.
This preclinical success is a crucial step for Silexion and potentially for patients battling KRAS-driven cancers, especially pancreatic cancer, which is known for its aggressiveness and poor prognosis. Systemic administration, if proven effective in later trials, offers a less invasive and potentially more effective way to reach and treat tumors compared to localized treatments, potentially improving patient outcomes and quality of life. It also broadens the potential application of SIL-204 to metastatic disease, a significant challenge in cancer treatment.
Key preclinical findings include a 50% tumor growth reduction and 50% complete necrosis observed in mice with human pancreatic tumors harboring the G12D KRAS mutation after 30 days of treatment with an extended-release formulation of SIL-204. Subcutaneous administration also inhibited tumor growth in orthotopic mouse models of metastatic pancreatic cancer. Importantly, a single systemic dose maintained therapeutic drug levels in rat plasma and tissues for over 56 days. SIL-204 effectively targets multiple KRAS mutations (G12D, G12V, G12R, Q61H, and G13D), expanding its potential patient population. Separate studies using intratumoral administration of SIL-204 microparticles further demonstrated its anti-tumor activity.
These results position SIL-204 as a potential next-generation therapy for KRAS-driven cancers. Silexion’s plan to expand the development program based on these findings suggests the company is optimistic about the drug’s potential to progress to clinical trials and eventually offer a new treatment option for patients with these difficult-to-treat cancers. The extended release formulation and demonstrated ability to target multiple KRAS mutations could differentiate SIL-204 from existing therapies, potentially leading to improved efficacy and broader applicability in the treatment landscape.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
