Silexion Therapeutics Receives Israeli Regulatory Approval for Phase 2/3 Trial of KRAS-Targeting RNAi Therapy SIL204
核心洞察
Silexion Therapeutics (搜索) received formal approval from the Israeli Ministry of Health to initiate a Phase 2/3 clinical trial of SIL204 for locally advanced pancreatic cancer, marking a critical regulatory milestone for the KRAS (搜索)-targeting RNAi therapy.
SIL204 demonstrated significant anti-tumor activity across eight distinct KRAS (搜索) mutations and four cancer types in preclinical studies, with the therapy designed to target over 90% of pancreatic cancers that harbor KRAS mutations.
The planned Phase 2/3 study will begin in the second quarter of 2026 with an initial safety run-in cohort of approximately 18 patients, followed by a randomized cohort of approximately 166 patients evaluating dual-route administration with standard chemotherapy.
Silexion Therapeutics (搜索) Corp. has achieved a significant regulatory milestone with formal approval from the Israeli Ministry of Health to initiate its Phase 2/3 clinical trial evaluating SIL204 for the treatment of locally advanced pancreatic cancer. This approval represents a critical advancement for the clinical-stage biotechnology company, enabling the transition of its next-generation RNAi therapy into human clinical evaluation.
The approval follows extensive preclinical validation demonstrating SIL204's broad therapeutic potential across KRAS (搜索)-driven cancers. Throughout 2025, Silexion generated additional preclinical data showing that SIL204 demonstrated very high inhibition levels of cancer cell growth across multiple models and showed activity against eight distinct KRAS mutations: G12D, G12V, G12R, G12C, G13C, G12A, Q61H, and G13D. Preclinical efficacy was observed across four cancer types, including pancreatic, colorectal, lung, and gastric cancers.
Targeting the "Undruggable" KRAS Oncogene
SIL204 is designed to silence KRAS (搜索) mutations, which are present in over 90% of pancreatic cancers and are widely recognized as one of the most challenging targets in oncology. Unlike mutation-specific approaches, SIL204 is engineered to target a broad range of KRAS mutations, supporting its potential applicability across multiple high-value cancer indications. In orthotopic pancreatic cancer models, systemic administration of SIL204 resulted in significant reductions in primary tumor growth and metastatic spread to secondary organs.
"The receipt of this approval marks a defining and highly significant milestone for Silexion," said Ilan Hadar, Chairman and Chief Executive Officer of Silexion Therapeutics (搜索). "We are now advancing SIL204 into a pivotal clinical trial with the goal of addressing KRAS (搜索)-driven cancers at their source. This progress reflects the strength of our data, the safety demonstrated during the Loder (predecessor to SIL204) clinical trial, the urgency of the unmet need in pancreatic cancer, and our continued execution toward developing a potentially transformative therapy."
Phase 2/3 Trial Design and Timeline
The planned Phase 2/3 clinical study is expected to begin in the second quarter of 2026 and will include an initial safety run-in cohort of approximately 18 patients, followed by expansion into a randomized cohort of approximately 166 patients. The study is designed to evaluate SIL204's dual-route administration approach in combination with standard chemotherapy in patients with locally advanced pancreatic cancer.
The company remains on track to initiate the Phase 2/3 clinical trial in the first half of 2026, with Israel regulatory feedback anticipated by the end of the first quarter of 2026. Silexion also plans to submit a Phase 2/3 clinical trial application in Germany by the end of the first quarter of 2026, with additional regulatory filings across the European Union planned in early 2027.
Clinical Readiness Milestones Achieved
During the fourth quarter of 2025, Silexion achieved key clinical readiness milestones including completing two-species GLP toxicology studies for SIL204, supporting planned regulatory submissions and Phase 2/3 clinical readiness. The company also received written Scientific Advice from Germany's Federal Institute for Drugs and Medical Devices (BfArM) regarding the design of its planned Phase 2/3 clinical trial.
Silexion has engaged AMS Advanced Medical Services GmbH (搜索) as contract research organization (CRO) for its planned Phase 2/3 program and advanced manufacturing and operational partnerships to support scaled clinical execution. The company completed GMP production batches of the active pharmaceutical ingredient (API) and formulation development intended to support initiation of the planned human clinical trial.
Financial Position and Market Standing
During 2025, the company raised over $18.6 million in aggregate gross proceeds through public offerings and warrant exercises transactions. As of December 31, 2025, Silexion had cash and cash equivalents of $6.0 million, compared to $1.2 million as of December 31, 2024. The company believes that its current cash balance will support its continued advancement toward the initiation of the Phase 2/3 clinical trial expected in the second quarter of 2026.
In September 2025, Nasdaq confirmed that Silexion had regained full compliance with Listing Rules 5550(a)(2) and 5550(b)(1), securing continued listing on the Nasdaq Capital Market. Total shareholders' equity was $2.6 million as of December 31, 2025, compared to a capital deficiency of $(4.0) million as of December 31, 2024.
Research and development expenses for the year ended December 31, 2025, were $7.1 million, compared to $5.8 million for the year ended December 31, 2024. The increase was primarily driven by higher subcontractor and consultant expenses related to GMP production batches and formulation development intended to support the planned clinical trial initiation.
"We made meaningful progress during the fourth quarter and throughout 2025 as we executed across scientific, operational, and regulatory priorities to advance SIL204 toward the clinic," commented Hadar. "With our toxicology package completed, written Scientific Advice from Germany, and the submission of our Phase 2/3 clinical trial application in Israel, we believe we are well-positioned to continue advancing toward our planned Phase 2/3 clinical program initiation in 2026."