Silexion secures BfArM approval for SIL204 Phase 2/3 LAPC trial
Silexion Therapeutics has received unconditional approval from Germany's Federal Institute for Drugs and Medical Devices (BfArM) to initiate a Phase 2/3 clinical trial of SIL204 in patients with locally advanced pancreatic cancer (LAPC). The decision, issued under EU Clinical Trials Regulation 536/2014 with Germany acting as Reporting Member State, follows a positive opinion from the Ethics Committee of the North Rhine Medical Association and mirrors an earlier authorisation from the Israeli Ministry of Health granted in March 2026.
With both regulatory clearances now in hand, the NASDAQ-listed company says it expects to dose its first patient within weeks, with the initial site to be determined by whichever of the activated centres in Israel or Germany completes contracting and budget arrangements first. Site activation in Israel is led by Sheba Medical Center and Tel Aviv Sourasky Medical Center; German oncology centres are being enrolled under the harmonised EU Clinical Trials Information System (CTIS) framework, which also opens a pathway for Silexion to extend the programme to additional EU member states without separate national submissions.
Trial design and target biology
SIL204 is a small interfering RNA (siRNA) designed to suppress KRAS, the oncogenic driver present in approximately 90% of pancreatic cancers. The candidate uses what Silexion describes as a dual-route administration strategy, pairing intratumoral delivery to address the primary tumour with systemic administration intended to reach metastatic disease. The Phase 2/3 study will open with a safety run-in cohort of around 18 patients receiving SIL204 in combination with standard-of-care chemotherapy, before expanding to a randomised cohort of approximately 166 patients.
Ilan Hadar, chairman and chief executive, said the unconditional BfArM clearance represents "a strong external validation of the SIL204 preclinical and safety package," noting the agency's rigorous reputation and its prior provision of written scientific advice in December 2025. Two-species toxicology studies, completed before the Clinical Trial Application was submitted in April 2026, showed no systemic organ toxicity.
Market context and competitive landscape
Pancreatic cancer remains among the most lethal solid tumours, with a five-year survival rate below 13% and limited improvement in outcomes over the past decade. KRAS has long been considered undruggable, but that consensus has shifted materially. Amgen's KRAS G12C inhibitor sotorasib and Mirati's adagrasib have demonstrated proof-of-concept in lung and colorectal cancers, and a growing cohort of companies, including Relay Therapeutics and Revolution Medicines, are advancing pan-KRAS and multi-switch inhibitor programmes.
RNAi-based approaches represent a distinct mechanistic angle. Unlike small molecules that target a specific KRAS mutation at the protein level, siRNA candidates aim to silence KRAS expression upstream, which could in principle address the broader mutational spectrum seen in pancreatic cancer. The field remains early, and Silexion's prior Phase 2a study in a first-generation candidate showed a positive trend versus chemotherapy alone, though detailed comparative efficacy data have not been publicly released.
The dual-route delivery strategy is a clinically meaningful design choice given that more than 80% of pancreatic cancer mortality is attributable to metastatic spread, but it also adds procedural complexity and potential safety variables that the run-in cohort will need to characterise carefully. Investors and clinicians will watch for interim safety data and any signal on tumour response in the expansion cohort as the key near-term catalysts for the programme.