Announcement • Jun 23
Silexion Therapeutics Receives Approval from Germany's Bfarm to Initiate Phase 2/3 Clinical Trial of Sil204 in Locally Advanced Pancreatic Cancer Silexion Therapeutics Corp. has received formal approval from Germany's Federal Institute for Drugs and Medical Devices (BfArM, Bundesinstitut für Arzneimittel und Medizinprodukte) to initiate its planned Phase 2/3 clinical trial of SIL204, the Company's lead small interfering RNA (siRNA) product candidate, in patients with locally advanced pancreatic cancer (LAPC). The trial has been approved without conditions, with both Part I and Part II of the assessment determined to be justifiable, following the positive opinion of the Ethics Committee of the North Rhine Medical Association regarding the conduct of the trial in Germany. The decision was issued under Articles 5 and 8 of EU Regulation No. 536/2014 in conjunction with the German Medicines Act (AMG), with Germany serving as the Reporting Member State (rMS) leading the scientific assessment of the trial under the EU Clinical Trials Regulation. The approval follows the Company's April 2026 submission of its Clinical Trial Application (CTA) through the EU Clinical Trials Information System (CTIS), which was informed by the positive written Scientific Advice from BfArM received in December 2025, the previously announced completion of two-species toxicology studies confirming no systemic organ toxicity, and the Company's broader preclinical package. The decision also builds on the March 24, 2026 approval from the Israeli Ministry of Health, which authorized initiation of the same Phase 2/3 trial in Israel. With the assessment in Germany complete, Silexion is now positioned to potentially expand its Phase 2/3 program across additional EU member states under the harmonized CTIS framework. With both regulatory authorizations now obtained, Silexion is finalizing site activation procedures at participating medical centers in Israel and Germany, including the contracting and budget arrangements customary for multi-site international trials of this scale. The Company expects first-patient dosing to occur in the coming weeks, with the initial dosing site to be determined by the timing of site activation across the participating centers. Site activation in Israel is led by Sheba Medical Center and Tel Aviv Sourasky Medical Center, both of which previously received local ethics approvals for the trial, with German oncology centers being brought into the program under the EU CTIS framework. The Phase 2/3 trial is designed to evaluate SIL204 in combination with standard-of-care chemotherapy in patients with LAPC, using Silexion's innovative dual-route administration strategy - combining intratumoral delivery to target primary tumors with systemic administration to address metastatic disease. The study is structured as an initial safety run-in cohort of approximately 18 patients, followed by expansion into a randomized cohort of approximately 166 patients. Pancreatic cancer remains one of the most lethal malignancies, with a five-year survival rate below 13%, and more than 80% of pancreatic cancer mortality driven by metastatic disease. KRAS mutations are present in approximately 90% of pancreatic cancers, 45% of colorectal cancers, and 30–35% of lung adenocarcinomas, representing one of the largest and most persistent unmet needs in oncology. New Risk • May 22
New major risk - Revenue and earnings growth Earnings are forecast to decline by an average of 0.3% per year for the foreseeable future. This is considered a major risk. Ultimately, shareholders want to see a good return on their investment and that generally comes from sharing in the company's profits. If profits are expected to decline, then in most cases the share price will decline over time as well. In addition, if the company pays dividends it will also likely need to reduce or cut them, striking a dual blow to total shareholder returns. Currently, the following risks have been identified for the company: Major Risks Less than 1 year of cash runway based on free cash flow trend (-US$12m free cash flow). Share price has been highly volatile over the past 3 months (33% average weekly change). Earnings are forecast to decline by an average of 0.3% per year for the foreseeable future. Shareholders have been substantially diluted in the past year (475% increase in shares outstanding). Revenue is less than US$1m. Market cap is less than US$10m (US$1.58m market cap). Minor Risk Currently unprofitable and not forecast to become profitable over next 3 years (US$24m net loss in 3 years). Announcement • May 16
Silexion Therapeutics Corp Reports Positive Preliminary Immunotherapy Findings for SIL204 in KRAS-Driven Pancreatic Cancer Silexion Therapeutics Corp. announced positive preclinical findings from an ongoing translational immuno-oncology study evaluating its lead candidate, SIL204, in human KRAS-mutated pancreatic cancer cells. Preliminary results from a preclinical study demonstrated statistically significant increase in MHC-I expression following SIL204 treatment in human pancreatic and non-small cell lung cancer cells harboring a KRAS mutation, supporting potential future evaluation alongside anti-PD-1 therapies including pembrolizumab (Keytruda®). The study demonstrated a statistically significant increase in surface expression of major histocompatibility complex class I (MHC-I), also known as HLA-ABC, following treatment with SIL204 in human pancreatic cancer cells harboring the KRAS G12R mutation, as measured by flow cytometry. MHC-I is essential for enabling cytotoxic T cells to recognize and attack tumor cells. Loss or suppression of MHC-I expression is widely recognized as a key mechanism by which tumors evade immune detection and resist immune-mediated destruction. Research has shown that oncogenic KRAS signaling contributes to immune evasion through suppression of antigen presentation and impairment of T-cell recognition pathways in pancreatic cancer and other KRAS-driven tumors. Pancreatic cancer remains among the most immunologically resistant solid tumors and has historically demonstrated limited responsiveness to immune checkpoint inhibitor therapies such as anti-PD-1 agents, including pembrolizumab (Keytruda®), outside of select biomarker-defined patient populations. By increasing MHC-I expression, SIL204 may help restore immune visibility of KRAS-mutated tumor cells, potentially supporting future therapeutic strategies designed to enhance responsiveness to PD-1/PD-L1 blockade. Published research has increasingly highlighted the relationship between KRAS signaling, antigen presentation, and immune checkpoint resistance, with multiple recent studies suggesting that reversing KRAS-associated immune suppression may improve immune-mediated anti-tumor activity. SIL204 increases surface MHC-I (HLA-ABC) expression in human KRAS G12R-mutated pancreatic cancer cells (KP2-G12R) at 60 nM, as measured by flow cytometry. 
