Silencing Oncogenes at the Level of Gene Expression Nasdaq: SLXN Corporate Presentation March, 2025

The statements contained in this presentation that are not purely historical are forward-looking statements. Our forward-looking statements include, but are not limited to, statements regarding our or our management team’s expectations, hopes, beliefs, intentions or strategies regarding the future. In addition, any statements that refer to projections, forecasts or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predict,” “project,” “should,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. Forward-looking statements in this presentation may include, for example, statements about: the future performance of the Company, including Silexion’s projected timeline for regulatory approvals of its product candidates; and the Company’s future plans and opportunities. The forward-looking statements contained in this presentation are based on our current expectations and beliefs concerning future developments and their potential effects on us. There can be no assurance that future developments affecting us will be those that we have anticipated. These forward-looking statements involve a number of risks, uncertainties (some of which are beyond our control) or other assumptions that may cause actual results or performance to be materially different from those expressed or implied by these forward-looking statements. These risks and uncertainties include, but are not limited to, the items in the following list: Silexion is a development-stage company and has a limited operating history on which to assess its business; Silexion has never generated any revenue from product sales and may never be profitable; The approach Silexion is taking to discover and develop novel RNAi therapeutics is unproven for oncology and may never lead to marketable products; Silexion does not have experience producing its product candidates at commercial levels, currently has no marketing and sales organization, has an uncertain market receptiveness to its product candidates, and is uncertain as to whether there will be insurance coverage and reimbursement for its potential products; Silexion may be unable to attract, develop and/or retain its key personnel or additional employees required for its development and future success; Additional factors relating to the business, operations and financial performance of Silexion. Should one or more of these risks or uncertainties materialize, or should any of our assumptions prove incorrect, actual results may vary in material respects from those projected in these forward-looking statements. We undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required under applicable securities laws. 2 Forward-Looking Statement

Company Overview Silexion’s siRNA platform technology is designed to silence oncogenes and prevent the production of the mutated KRAS proteins that drive cancer growth First generation, SiG12DLoder siRNA Completed Phase 2 clinical trial, shows strong trend for 9.3 months improvement in overall survival with siG12DLoder + SoC chemo vs. SoC chemo alone Second generation, SIL204 siRNA Improved stability, broader silencing against various KRAS mutations Successful preclinical results in metastatic models with subcutaneous administration and primary tumor models with intratumor administration Phase 2/3 clinical trial, planned Q1, 2026, using comprehensive integrated approach administering systemic (subcutaneous) and intratumor administration Listed on Nasdaq on August 2024 Late-Stage Ready Asset with Regulatory Path Forward Clinical-stage company developing proprietary treatments for KRAS-driven cancers KRAS-Focused RNA Interference Platform Promising Clinical Data in Locally Advanced Pancreatic Cancer and preclinical results for optimized product Compelling investment proposition

KRAS Oncogene is a Validated Target for Numerous Cancers 4 Prevalence of The Most Common Types of KRAS Mutations Across Cancers CRC=colorectal cancer; LAPC=locally advanced pancreatic cancer; NSCLC=non-small cell lung cancer. Lee, J.K. et al. NPJ Precis Oncol. 2022;6(1):91. PDAC CRC Non-sq NSCLC Small Bowel Adenocarcinoma Appendix KRAS is the most common oncogenic gene driver in human cancers with gastrointestinal cancers having high percentages of KRAS G12D/V mutations % KRAS mutations 92% 49% 35% 53% 61%

Pancreatic Cancer Has One of the Highest Mortality Rates of All Major Cancers BRPC=borderline resectable pancreatic cancer; LAPC = locally advanced pancreatic cancer. 1. Bray F, et al. CA Cancer J Clin. 2024;74(3):229-263. 2. Hirshberg Foundation for Pancreatic Cancer Research. Pancreatic cancer Facts. https://pancreatic.org/pancreatic-cancer/pancreatic-cancer-facts. 3. National Cancer Institute. Cancer Stat Facts: Pancreatic Cancer. https://seer.cancer.gov/statfacts/html/pancreas.html. 4. Gemenetzis G, et al. Ann Surg. 2019;270(2):340-347. 5. Kleeff J, et al. Nat Rev Dis Primers. 2016;2:16022. Local Metastatic At diagnosis: 10-20% resectable 30-40% LAPC + BRPC 50-60% metastatic or systemic Types and Prevalence of Pancreatic Cancer4,5 5 There are no effective treatment options for our intended indication LAPC 3rd leading cause today in the U.S.2 2nd leading cause by 20302 12.8% 5-year relative survival (2014-2020) is one of the poorest in the U.S.3 Median overall survival for non-resectable PC populations is 14-17 months4

Innovatively Treating the Cancer-Driving KRAS at the Source and Site of Action Moving closer to treating the mechanism of the cancer more efficiently and with a greater chance to overcome treatment-resistance Cell proliferation Migration Transformation Survival Silexion siRNA Intratumor delivery KRAS small molecule inhibitors (Systemic delivery) Functional mutated KRAS protein Mutated KRAS mRNA Cancer Progression Mutated KRAS gene Inhibits oncogenic protein after its functioning Transcription Translation mRNA destroyed, no oncogenic KRAS mutant protein is made

Silexion Innovative Oncological Approach May Lead to Significant Improvement in Clinical Outcomes Over KRAS Inhibitors Treatment resistance Low tolerability with adverse events such as rashes and GI side effects that require special monitoring Limited overall response rate and progression-free survival Limitation of currently approved and investigational small molecule KRAS inhibitors: Inhibit oncogenic KRAS synthesis before it is active Integrated Treatment Regimen to more effectively treat both the primary tumor and micrometastases Optimized siRNA to enhanced stability and broader activity while maintaining good safety Silexion’s Approach

SIL204 is the Most Advanced siRNA Formulation for LAPC With a Significant Market Opportunity KRAS mutations are present in ~92% pancreatic cancer cases1 ROW=rest of the world. *Number of KRAS G12D/V mutated LAPC were calculated based on KRAS mutations being present in 92% of pancreatic cancer patients, 70-75% with KRAS G12D and G12V mutations and 30-35% of cases being LAPC. 1. Lee, J.K. et al. NPJ Precis Oncol. 2022;6(1):91. 2. Yousef, A. et al. NPJ Precis Oncol. 20024;8(1):27. 3. Global Cancer Observatory. Pancreatic Cancer. 2022. https://gco.iarc.who.int/media/globocan/factsheets/cancers/13-pancreas-fact-sheet.pdf. 4. National Cancer Institute. Cancer Stat Facts: Pancreatic Cancer. 2023. https://seer.cancer.gov/statfacts/html/pancreas.html. SIL204 targets > 74% of KRAS mutations in PDAC2 while currently available KRAS G12C treatment are treating ~1.5% Total Addressable Market in Localized Advanced Pancreatic Cancer U.S. E.U. Annual pancreatic caner cases 66,4004 146,4773 KRAS-G12D/V mutated LAPC incidence* ~16,000 ~35,000 8 U.S. ~$2B E.U ~$3B

LODER (First generation siRNA) Phase 2 Clinical Trial Data

Phase 2 Trial of Loder Completed in 2023 – a Proof-of-Concept Two-part, open label, study of LODER + SoC chemotherapy vs SoC chemotherapy alone across the U.S. and Israel in patients with non-resectable pancreatic cancer SoC=standard of care. Arm 1: LODER + SOC Chemo (n=18) Day 0 Randomization Long-term follow up Screening Death Determination of eligibility First LODER administration ~7 days later 1st chemo Week 8 – 1st CT Arm 2: SOC Chemo (n=11) Every 12 weeks – LODER administration Every 12 weeks – CT Screening Death Determination of eligibility First LODER administration ~7 days later 1st chemo Week 8 – 1st CT Arm 2: LODER + SOC Chemo (n=20) Every 12 weeks – LODER administration Every 12 weeks – CT Long-term follow up Cohort 1 (randomized) Cohort 2 (single arm) Key inclusion criteria Non-resectable without signs of metastasis ECOG Status ≤ 1 Both cohorts all patients meeting inclusion/exclusion criteria randomized without checking for KRAS mutation status Endpoints Overall survival (OS) Response rate (RR, RECIST v1.1) Safety Tolerability 10

Baseline Characteristics and Cohorts Information Due to results of a clinical trial indicating FOLFIRINOX’s advantage over GnP as SoC chemotherapy, cohort 2’s SoC chemotherapy was changed from GnP (used in cohort 1) to FOLFIRINOX. BRPC=borderline resectable pancreatic cancer; GnP=gemcitabine/nab-paclitaxel; LAPC=locally advanced pancreatic cancer; SoC=standard-of-care. *KRAS mutations were determined in 31 patients in total. In cohort 1, 12 patients in the treatment arm and 10 patients in the control arm were tested; in cohort 1, 9 patients were tested. Cohort 1 (n=29) Cohort 2 (n=20) Design/Arms Randomized, controlled (SoC) Single arm Population Locally advanced PC (LAPC) Non-resectable (BRPC+ LAPC) Nationality 62% U.S. ( 4 sites) , 38% Israel (5 sites) Male/ Female % 42% male; 58% female Median age (years) 69.7 64.9 KRAS Mutations G12D/V*: Loder 11/12, Control 5/10 G12R*: Loder: 1/12, Control 5/10 G12D/V*: Loder 7/9 G12R*: Loder: 2/9 Avg Loder cycles 2.8 2.1 Total number of Loder injections 370 SoC chemotherapy gemcitabine/nab-paclitaxel (GnP) (modified) FOLFIRINOX ((m)FFX) 11

Loder Treatment Led to Robust Objective Response Rate in Patients with LAPC Harboring G12D/V Mutations* LAPC=locally advanced pancreatic cancer. *Overall response rate was confirmed by RECIST 1.1 of the target tumor, as analyzed by sites. Bar curves below the solid black line starting at y-axis -0.3 indicates criteria for positive RECIST response. Chemo: Loder: R = Non-resectable tumor becomes resectable G12D G12V Cohort 1 Cohort 1+2 Best % change in tumor size from baseline Cohort 1 LODER+Chemo Cohort 1+2 LODER+Chemo Chemo % Response 55 (6/11) 56 (10/18) 20 (1/5) % Response+ becoming resectable 64 67 40

Cohort 1 Patients Treated with Loder Had 9.3 Months Improvement in Overall Survival 13 * SoC (Control) OS consistent with recent trials for LAPC (Gemenetzis G, et al. Ann Surg. 2019;270(2):340-347). Hazard ratio (HR)=0.59, (95% CI, 0.18, 1.96, p=0.39) Time to death is slower, 41% reduction in the rate of mortality. Patients living longer with Loder+SOC vs. SOC Days Overall Survival in Cohort 1 SOC chemo median =13.4 mo.* siRNA+SOC chemo median=22.7 mo.

Phase 2 Safety Results Serious Adverse Events (SAEs) Related to Treatment in Patients with LAPC who Received LODER + Chemotherapy (treatment plus EUS-endoscopy administration procedure) LODER + SOC chemo (n=38) SAE All grades n (%) Grades 3-4 n (%) Gastrointestinal disorders 3 (8%) 2 (5%) Hematemesis 1 (3%) 0 (0%) STOMACH ACUTE PAIN 1 (3%) 1 (3%) Gastric hemorrhage 1 (3%) 1 (3%) General disorders and administration site conditions 2 (5%) 0 (0%) Fever 2 (5%) 0 (0%) Hepatobiliary disorders 3 (8%) 2 (5%) Cholangitis 2 (5%) 1 (3%) Obstructive Hyperbilirubinemia 1 (3%) 1 (3%) Infections and infestations 2 (5%) 2 (5%) Sepsis 1 (3%) 1 (3%) Pancreas infection 1 (3%) 1 (3%) Depression 1 (3%) 1 (3%) Injury, poisoning and procedural complications 1 (3%) 1 (3%) procedural hemorrhage 1 (3%) 1 (3%) Nervous system disorders 1 (3%) 1 (3%) Presyncope 1 (3%) 1 (3%) 14

LODER Was Overall Well Tolerated The Phase 2 PoC clinical trial investigators reported that LODER treatment was well tolerated; Safety events were primarily related to procedure Intratumor administration of extended-release siRNA via endoscopy (EUS) is safe No Treatment Emergent Adverse Events (TEAEs) leading to study discontinuation related to LODER treatment No meaningful observations in any vital sign parameter nor any physical examination findings in the study Independent Drug Safety Monitoring Board (DSMB) Reviews had no safety concerns nor safety restrictions In a subset analysis, no measurable amount of LODER was detected (<BLQ) in any plasma samples suggesting low systemic levels 15

Optimizations allows for comprehensive approach: systemic and intratumor administrations siRNA: Successful preclinical results in metastatic models with subcutaneous administration and primary tumor models with intratumor administration Enhanced stability Broadening silencing activity

Leveraging LODER Clinical Data to Further Improve SIL204 Potential Efficacy and Safety 17 HR=Hazard Ratio. *EUS endoscopy is a standard procedure used to obtain ultrasound guided biopsies once every 3 months. ` LODER SIL-204 siRNA target KRAS G12D/V+ KRAS amplify KRAS G12D/V+ KRAS amplify, potential pan KRAS Stability in human serum (HS) and rat pharmacokinetics HS <1 hr HS > 48 hrs, Remains at substantial levels for >56 Days in plasma and tissues after single subcutaneous administration to rats Access to tumor cell site of action No hydrophobic lead Added hydrophobic lead to increase siRNA access into cell Route and Ease of administration EUS-endoscopy* with larger needle; Required loading device S.C. administration and EUS Endoscopy* with smaller and more flexible needle; No loading device needed Improvement in OS with chemo vs. chemo alone + 9.3 monthsHR=0.59 Reduction in rate of death by 41% compared to chemotherapy alone TBD in Phase 2/3 trial with expected improvement in OS Safety Generally well tolerated; Safety events were primarily related to procedure Expectations for similar safety profile

SIL204 Shows Broad Inhibition Across Human KRAS Mutations at Sub-Nanomolar Concentrations SIL204 maintains and expands the silencing activity of the siG12DLoder 18 Model is a co-transfection setup where human KRAS is transfected in mouse Hepa1-6 cells with Dual-Glo reporter plasmids. Mutation NegativesiRNAControl WT KRAS KRAS G12D KRAS G12V KRAS G12C KRAS G12R KRAS Q61H* KRAS G13D* IC50 (nM) 0.16 0.19 0.44 0.47 0.59 0.24 0.37 MAX Inhibition (%) 0-7 91 90 80 73 71 88 88 IC50=half-maximal inhibitory concentration. *G13D and Q61H tested in separate studies from the G12 mutations and wild type (non-mutated). Negative siRNA control collected over various studies

SIL204 is Stable In Vitro for Over 48 Hours in Human Serum 19 siRNA strand placed in human serum and tested for stability Stability of siRNA Strand in Human Serum Potentially longer effectiveness of siRNA Greater ability to diffuse throughout the fibrous tumor environment Potential in other indications Previous studies have shown siG12D (LODER) half-life to be 5 min in human serum.

SIL204 Remains at Substantial Levels for >56 Days in Plasma and Tissues Single subcutaneous administration SIL204 solution (10mg, not formulated) to Sprague Dawley rats 20 Potential for longer effectiveness of siRNA for treating micrometastases with clinical dosing on monthly basis

SIL204 Behaves Synergistically with Fluorouracil and Irinotecan-Containing Chemotherapy *p<0.05; ** p<0.005; ***p<0.0005 Basis for first line chemotherapy for pancreatic cancer. Preclinical study measuring confluence of the human pancreatic cell line Panc-1 containing a G12D KRAS Mutation 21 *** ** * *** *

Intratumor Administered SIL204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice *p<0.05 ; ***p<0.0005 S.C. = sub cutaneous. SIL204 significantly reduced tumor volume and growth while increasing tumor necrosis (cell death) Day 1: Capan-1 (KRAS G12V) luciferase cells were xenografted to mice (s.c.) concurrently with SIL204 formulated in extended-release microparticles Days 3-15: mice were evaluated for bioluminescence to evaluate relative tumor cell counts Day 15: tumors were removed, area determined and analyzed by histology for % necrosis from tumor center slice 22 % Necrosis 5.5 4.5 3.5 2.5 1.5 0.5 Bioluminescence (106) Tumor area (mm2) * ***

Systemic Administration of siRNA Strongly Supported by Preclinical Data 23 Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic Models Animal model represents human equivalent dose of SIL-204 High dosage subcutaneous injection of SIL204 ablated xenograft tumor * Human tumor cell line Panc-1 harboring KRAS G12D mutation Control High dose SIL204

Systemic Administration of siRNA Strongly Supported by Preclinical Data 24 Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic ModelsAnimal model represents the human equivalent dose of SIL-204 Low dosage subcutaneous injection of SIL-204 inhibited tumor growth * Human tumor cell line AsPc-1 harboring KRAS G12D mutation

Systemic Administration of siRNA Strongly Supported by Preclinical Data 25 Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic Models Animal model represents human equivalent dose of SIL-204 * Human tumor cell line BxPC-3 Control Low dose SIL204

SIL204 Development Strategy in LAPC 2023 2024 H1 2025 H2 2025 H1 2026 H2 2026 Clinical proof of concept for Loder in LAPC in an approvable endpoint for FDA Optimization of siRNA on various fronts; selection of SIL-204 Received guidance on trial design from the German Federal Institute for Drugs and Medical Devices (BfArM), intratumor administration Initiate toxicology studies SIL-204 GMP production API (SIL-204) Submit CTA in E.U. for Phase 2/3 Initiate Phase 2/3, LAPC Germany/Israel Leverage safety clinical data from first trial segment Phase 2/3 Pre-IND meeting FDA Submit IND to FDA Expand Phase 2/3 to USA\additional EU, etc 26 Indicates completed activity. Unmarked activities to be performed. Meeting with German authorities for regulatory buy-in/scientific advice (BfArM) on integrated regimen, and plans to proceed to Phase 2/3 trial GMP production injectable formulation Meeting with Israel Health authorities planned to discuss program

Program Indication Setting Discovery Preclinical Phase 1 Phase 2 Phase 3 Status/ Anticipated Milestone LODER siG12D + KRAS amplify with extended release PLGA delivery system Locally advanced pancreatic cancer Adjunct to chemotherapy Phase 2 completed: observed 9.3 months improvement with LODER over SOC. Continue development of SIL204. SIL204 (Integrated treatment regimen) KRAS G12D/V + KRAS amplify Locally advanced pancreatic cancer Adjunct to chemotherapy Q1 2026: CTA submission in E.U. for Phase 2/31H 2026: Initiate Phase 2/3 Colorectal cancer Adjunct to chemotherapy H2 2025: Initiate preclinical SIL204 adjunct to CPIs KRAS-driven cancers Adjunct to CPI+ chemotherapy H2 2025: Initiate preclinical Focused Pipeline to Address KRAS-driven Solid Tumor Localized Cancers 27 CTA=clinical trial application; SOC=standard of care. Phase 2 Completed Current Focus: Second generation SIL204

Strong Intellectual Property Protection Exclusivity can be extended under country-specific regulatory-based extension rules. Submissions Term Patents supporting siG12DLoder 10 patents issued world-wide, 6 patients pending. Protection until 2030 plus extension Patents supporting SIL204 Inhibition of KRAS expression and methods of use thereofinclude composition of matter, positive patent office review Compositions for inhibition of KRAS expression and treatment regiments therewith PCT (PCT/ IL2023/051276). Expected protection 2043 plus estimated extension up to 2048) Provisional (anticipated up to at least 2046 plus extension) siRNA against KRAS G12x for regional perineural invasion or pain associated with a solid tumor Pending US/EU, expected term till 2040 plus extension

World-Renowned Expert Scientific Advisory Board Eileen M. O'Reilly, MD Memorial Sloan Kettering, NY, NY Winthrop Rockefeller Endowed Chair of Medical Oncology; Co-Director, Medical Initiatives, David M. Rubenstein Center for Pancreatic Cancer Research; Section Head, Hepatopancreatobi Hana Algul, MD Technical University of Munich, Germany chair for tumor metabolism; Director of the Comprehensive Cancer Center Munich, Germany at the Klinikum rechts der Isar, and Mildred-Scheel-professor and Milind Javle, MD The University of Texas & MD Anderson Cancer Center, Houston, TX Professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine Philip A. Philip, MD Henry Ford Health, Detroit, MI Director, Gastrointestinal Oncology; Co-Director, Pancreatic Cancer Center; Medical Director, Research and Clinical Care Integration, Henry Ford Cancer Institute Talia Golan, MD Sheba Tel Hashomer Hospital,, Israel Head, Sheba Pancreatic Cancer Center - SPCC Matthew Katz, MD The University of Texas & MD Anderson Cancer Center, Houston, TX Department Chair, Department of Surgical Oncology, Division of Surgery and Professor. Andrew M. Lowy, MD UC San Diego, San Diego, CA Chief, Division of Surgical Oncology; Professor of Surgery Mark A. Schattner, MD Memorial Sloan Kettering, NY, NY Chief, Gastroenterology, Hepatology and Nutrition Service 29 Thomas Seufferlein, MD University Hospital Ulm, German Director of Internal Medicine University Hospital Ulm, President German Cancer Society

Highly Experienced Leadership Team Ilan Hadar, MBA Chairman and Chief Executive Officer > 25 years of multinational managerial and corporate experience with pharmaceutical and high-tech companies Mitchell Shirvan, PhD, MBA Chief Scientific and Development Officer > 30 years of experience in R&D, innovation and discovery in biotech companies Mirit Horenshtein Hadar, CPA Chief Financial Officer > 15 years of corporate finance experience in senior financial positions of public companies and privately held companies, in the pharmaceutical and high-tech industries 30

Investment Highlights CTA=clinical trial application; IND=investigational new drug. Clinical-stage company with proprietary oncogene silencing siRNA platform Phase 2 clinical trial with first generation Loder in LAPC showed strong trend for 9.3 months improvement in survival Second generation SIL204 with enhanced siRNA stability, broader activity, successful preclinical models Integrated Treatment Regimen to more effectively treat both primary tumor and secondary micrometastases proof-of concept to target metastasis with subcutaneous administration Comprehensive integrated treatment regimen planned for pivotal trials Advanced RNA therapeutic candidate in oncology Late-Stage Ready Asset with Regulatory Path Forward Strong Partnerships with Solid IP Portfolio Guidance received from German Federal Institute for Drugs and Medical Devices (BfArM) on Phase 2/3 trial Submit CTA in E.U. in 1H 2026 and initiate Phase 2/3 trial of SIL204 in 1H 2026 Extension Phase 2/3 trial to U.S. H2, 2026 Established partnerships for GMP production of siRNA and formulations PCT submitted with favorable international review for claims for siRNA composition of matter and use, IP exclusivity through December 2043 plus extension (potential term to 2048)

Thank You Nasdaq: SLXN Ilan Hadar Chairman & Chief Executive Officer email: ihadar@silexion.com Dr. Mitchell Shirvan Chief Scientific and Development Officer email: mshirvan@silexion.com Mirit Horenshtein Hadar, CPA Chief Financial Officer email: mirit@silexion.com