Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (September 2025)
32 slides from Silexion Therapeutics's investor presentation, Sep 2, 2025
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Silencing Oncogenes at the Level of Gene Expression Nasdaq: SLXN Corporate Presentation August 2025
Slide 2: Forward-looking statements
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.
Slide 3: Silencing Cancer-Driving Proteins Before They Are Produced
Silexion: Silencing Cancer-Driving Proteins Before They Are Produced Mutated KRAS proteins are the most prevalent cancer drivers: 92% pancreatic cancer 49% colorectal cancer 35% non-small-cell-non-squamous lung cancer They are well-validated targets, as KRAS inhibitor products represent a multi-bill
Slide 4: Phase 2 Proof-of-Concept Paves the Way for Late-Stage Development
Silexion’s Phase 2 Proof-of-Concept (POC) Paves the Way for Late-Stage Clinical Development First generation, KRAS mutation G12D/G12V “Loder” silencing RNA (siG12DLoder siRNA) Completed POC- Phase 2 clinical trial in locally advanced pancreatic cancer (LAPC), shows strong trend for 9.3 months improv
Slide 5: Positioned to Develop the Most Advanced Oncogene Silencing Therapy
Silexion is Positioned to Develop the Most Advanced Oncogene Silencing Therapy NASDAQ listing – ticker SLXN Management team experienced with late-stage development Validated cancer target in mutated KRAS; KRAS-driven cancers represent large potential and need for oncogene silencing therapy in pancre
Slide 6: Targeting Mutated KRAS by Silencing RNA
Targeting Mutated KRAS by Silencing RNA 6
Slide 7: KRAS Oncogene is a Validated Target for Numerous Cancers
KRAS Oncogene is a Validated Target for Numerous Cancers 7 Most Common Types of KRAS Mutations Across Cancers Lee, J.K. et al. NPJ Precis Oncol. 2022;6(1):91. Pancreatic Ductal Adenocarcinoma (PDAC) Colorectal Cancer (CRC) Non-squamous Non-Small-Cell Lung Cancer(Non-sq NSCLC) KRAS is the most common
Slide 8: Pancreatic Cancer Among Highest Mortality Rates of Any Major Cancers
Pancreatic Cancer Among Highest Mortality Rates of Any 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
Slide 9: Focused Pipeline to Address KRAS-driven Solid Tumors
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
Slide 10: LODER (First generation siRNA) Phase 2 Clinical Trial Data
LODER (First generation siRNA) Phase 2 Clinical Trial Data 10
Slide 11: Phase 2 Proof of Concept Trial of Loder Completed in 2023
Phase 2 Proof of Concept Trial of Loder Completed in 2023 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
Slide 12: Loder Led to Robust Objective Response Rate in LAPC with G12D/V
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
Slide 13: Loder + SOC Chemotherapy Extends Median Survival
Loder + SOC Chemotherapy Extends Median Survival by 9 Months in KRAS G12D/V Mutations in POC Study 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) 41% lower risk of death at any ti
Slide 14: LODER Was Well Tolerated with Acceptable Safety Profile
LODER Was Overall Well Tolerated with an Acceptable Safety Profile Combination siG12D-LODER and SoC chemotherapy generally well-tolerated All serious TEAEs resolved: 9 (pyrexia x2, abdominal pain, hyperbilirubinemia, pancreas infection x2, sepsis, procedural hemorrhage/presyncope, gastric hemorrhage
Slide 15: SIL204 (Second Generation siRNA)
SIL204 (Second Generation siRNA) 15
Slide 16: Innovative Approach Expected to Improve Clinical Outcomes
Silexion Innovative Approach Expected to Improve Clinical Outcomes Treatment resistance Low tolerability with adverse events such GI side effects (e.g. diarrhea) and rashes and that require special monitoring Unmet need in survival and QoL remains Overcoming the Limitations of Currently Approved and
Slide 17: Dual Administration of SIL204 Designed to Eradicate Primary Tumor and Metastases
Dual Administration of SIL204 Designed to Eradicate Primary Tumor and Metastases Integrating systemic (s.c.) with intra-tumoral administration complement the effect of SIL204 on the primary pancreatic tumor with eradication of migrating metastatic cells Primary pancreatic tumor targeted by intratumo
Slide 18: SIL204 Anti-Tumor Activity Synergistic with SOC Chemotherapy
SIL204’s Anti-Tumor Activity Synergistic with Pancreatic Cancer SOC Chemotherapy *p<0.05; ** p<0.005; ***p<0.0005 Preclinical study measuring confluence of the human pancreatic cell line Panc-1 containing a G12D KRAS Mutation 18 *** ** * *** *
Slide 19: SIL204 In Silico Analysis: Highly Specific for KRAS
SIL204 In Silico Analysis: Highly Specific for KRAS vs Other RAS or Off-Target Sites Approach SIL204 must bind the KRAS mutation mRNA for activity Negative values indicate binding. Negative Gibb’s free energy changes (∆G) of -20s and 30s indicates strong, favorable binding KRAS G12V -31.8 kcal/mole
Slide 20: SIL204 Broad Inhibition Across Human KRAS Mutations
SIL204 Highly Effective with Broad Inhibition Across Human KRAS Mutations at Sub-nanomolar Concentrations SIL204 maintains and expands the silencing activity of the siG12DLoder 20 Model is a co-transfection setup where human KRAS is transfected in mouse Hepa1-6 cells with Dual-Glo reporter plasmids.
Slide 21: SIL204 Inhibits Human Tumor Cell Line Growth
21 SIL204 Inhibits Human Tumor Cell Line Growth at Concentrations Achievable with the Planned Clinical Trial Human Equivalent Doses Results support the pan-KRAS silencing activity observed in transfected hepa cells IC90 is the concentration for 90% inhibition of tumor cell growth, IC50 is the concen
Slide 22: Intratumor PK Data Confirm Durable SIL204 Exposure
Human pancreatic tumors in mice (2 separate lines) administered by intratumoral injection 3mg SIL204/tumor (approximate human equivalent dose (HED) planned in the clinical trial) showed that the intratumoral concentrations are much higher than IC90 for a prolonged period Tumor levels from 3mg SIL204
Slide 23: Intratumoral HED SIL204 Shrinks Implanted KRAS G12V Tumors in Mice
Intratumoral SIL204 (3mg/tumor, planned P2/3 ~HED) reduced tumor size in nude mice bearing KRAS G12V xenograft Histological examination revealed a higher degree of tumor necrosis than in the untreated control group Results further support the dose to be used to effectively treat the primary tumor in
Slide 24: S.C. SIL204 PK Shows Persistent Exposure at Metastatic Site
S.C. SIL204 PK Demonstrates Persistent Effective Exposure at Major Metastatic Site 24 PK Studies in rats 10 mg/rat (~HED 400mg, the planned clinical s.c. dose) showed that s.c. injection slowly releases SIL204 SIL204 slowly distributes to other tissues, primarily to the liver (main site of metastasi
Slide 25: S.C. SIL204 Demonstrates Positive Dose Response in Tumor Volume
25 Responder analysis to SIL204 following SC injections in an orthotopic model. S.C. SIL204 Demonstrates Positive Dose Response in Tumor Volume Nude mice with orthotopic PANC-1 (KRAS G12D, luciferase) tumors showed dose-dependent tumor inhibition after subcutaneous (SC) SIL204 Three different defini
Slide 26: Subcutaneous SIL204 Shrinks Distal Metastases in Animal Model
Subcutaneous SIL204 Shrinks Distal Metastases in Animal Model 26 Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic Models Animal model represents human equivalent dose of SIL-204 * Human tumor cell line Panc-1 harboring KRAS G12D mutation Control Low dose SIL204 Reductio
Slide 27: Late-Stage Clinical Development Roadmap for SIL204 in Pancreatic Cancer
Late-Stage Clinical Development Roadmap for SIL204 in Pancreatic Cancer 2023 2024 H1 2025 H2 2025 H1 2026 H2 2026 Phase 2 Clinical proof of concept for prototype siRNA (Loder) in LAPC with trend survival, ORR Optimization of siRNA to improve efficacy and stability Initial Scientific Advice, German r
Slide 28: Strong Intellectual Property Protection
Strong Intellectual Property Protection Exclusivity can be extended under country-specific regulatory-based extension rules. Submissions Filing – Term-claims Patents supporting SIL204 Compositions for Inhibition of Kras Expression and Methods of Use Thereof.Main patent protection for SIL204Includes
Slide 29: Positioned to Develop the Most Advanced Oncogene Silencing Therapy
Silexion Positioned to Develop the Most Advanced Oncogene Silencing Therapy Late-Stage Ready Asset with Regulatory Path Forward Strong Partnerships with Solid IP Portfolio Instead of targeting mutated KRAS proteins after they are formed (as competing technologies do) Silexion’s siRNA technology sile
Slide 30: World-Renowned Expert Scientific Advisory Board
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
Slide 31: Highly Experienced Leadership Team
Highly Experienced Leadership Team Ilan Hadar, MBA Chairman and Chief Executive Officer Over 25 years of multinational executive managerial and corporate experience with pharmaceutical and high-tech companies. CEO PainReform (Nasdaq: “PRFX”), CFO and Country Manager Foamix Pharmaceuticals Inc. (Curr
Slide 32: Thank You
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 Chief Financial Officer email: mirit@silexion.com 32
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