Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (August 2025)
32 slides from Silexion Therapeutics's investor presentation, August 2025
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Silencing Oncogenes at the Level of Gene Expression Corporate Presentation August 2025 Nasdaq: SLXN
Slide 2: Forward-Looking Statements
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 strate
Slide 3: Silexion: 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 KRAS-Focused They are well-validated targets, as KRAS inhibitor products represent
Slide 4: Silexion's Phase 2 Proof-of-Concept Paves the Way for Late-Stage Clinical 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), Promising Clinical shows strong trend
Slide 5: Silexion is 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 Late-Stage Company • Validated cancer target in mutated KRAS; KRAS-driven cancers represent with Advanced large potential and need f
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 Most Common Types of KRAS Mutations Across Cancers Pancreatic Ductal Colorectal Cancer Non-squamous Non- Adenocarcinoma (CRC) Small-Cell Lung Cancer (PDAC) (Non-sq NSCLC) % KRAS mutations 92% 49% 35% Incidence USA+EU ~200K ~500K ~400K KRAS is
Slide 8: Pancreatic Cancer Among Highest Mortality Rates of Any Major Cancers
Pancreatic Cancer Among Highest Mortality Rates of Any Major Cancers Types and Prevalence of Pancreatic Cancer 4,5 Local Metastatic 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 fo
Slide 9: Focused Pipeline to Address KRAS-driven Solid Tumor Localized Cancers
Focused Pipeline to Address KRAS-driven Solid Tumor Localized Cancers Program Indication Setting Discovery Preclinical Phase 1 Phase 2 Phase 3 Status/ Anticipated Milestone Locally LODER Phase 2 completed: observed 9.3 months advanced Adjunct to Phase 2 Completed siG12D + KRAS amplify with extended
Slide 10: LODER (First generation siRNA)
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 Key inclusion criteria Arm 1: LODER + SOC Chemo (n=18) Long-te rm follow up • Non-r
Slide 12: Loder Treatment Led to Robust Objective Response Rate in Patients with LAPC
Loder Treatment Led to Robust Objective Response Rate in Patients with LAPC Harboring G12D/V Mutations* 0.5 0.5 0.4 0.4 Best % change in tumor size 0.3 0.3 0.2 0.2 0.1 0.1 from baseline 0 0 -0.1 -0.1 R R R -0.2 -0.2 R R -0.3 -0.3 -0.4 -0.4 R -0.5 -0.5 R -0.6 R -0.6 R R -0.7 -0.7 Cohort 1 Cohort 1+2
Slide 13: Loder + SOC Chemotherapy Extends Median Survival by 9 Months
Loder + SOC Chemotherapy Extends Median Survival by 9 Months in KRAS G12D/V Mutations in POC Study Overall Survival in Cohort 1 Hazard ratio (HR)=0.59, (95% CI, 0.18, 1.96, p=0.39) 41% lower risk of death at any time compared to SOC chemotherapy Implications siRNA+SOC chemo • 69% improvement in over
Slide 14: LODER Was Overall Well Tolerated with an 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 hemorr
Slide 15: SIL204 (Second Generation siRNA)
SIL204 (Second Generation siRNA) 15
Slide 16: Silexion Innovative Approach
Overcoming the Limitations of Currently Approved and Investigational Small Molecule KRAS Inhibitors: • Treatment resistance • Low tolerability with adverse events such GI side effects (e.g. diarrhea) and Silexion rashes and that require special monitoring Innovative • Unmet need in survival and QoL
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 • Pancreatic cancer mortality driven by early
Slide 18: SIL204's Anti-Tumor Activity Synergistic with Pancreatic Cancer SOC Chemotherapy
SIL204’s Anti-Tumor Activity Synergistic with Pancreatic Cancer SOC Chemotherapy Preclinical study measuring confluence of the human pancreatic cell line Panc-1 containing a G12D KRAS Mutation Panc1 cell confluence after 90 hrs Panc1 cell confluence after 67 hrs 45 *** 50 * 40 Cell Confluence 35 Cel
Slide 19: SIL204 In Silico Analysis: Highly Specific for KRAS vs Other RAS or Off-Target Sites
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 Conclusions • Negative values indicate binding. • SIL-204 will silence the intended target KRAS mutations, but low risk for any effect with other • N
Slide 20: SIL204 Highly Effective with 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 Model is a co-transfection setup where human KRAS is transfected in mouse Hepa1-6 cells with Dual-Glo reporter plasmids. N
Slide 21: SIL204 Inhibits Human Tumor Cell Line Growth at Achievable Concentrations
SIL204 Inhibits Human Tumor Cell Line Growth at Concentrations Achievable with the Planned Clinical Trial Human Equivalent Doses • SIL204 efficacy in tumor cells from 4 different human cancer cell lines: pancreatic; colon; lung and cholangiocarcinoma can be shown in a cell proliferation (CellTiter-G
Slide 22: Intratumor PK Data Confirm Durable SIL204 Exposure Above IC90
Intratumor PK Data Confirm Durable SIL204 Exposure Above GTC 100% Inhibition Target (IC90) 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 c
Slide 23: Intratumoral HED SIL204 Shrinks Implanted KRAS G12V tumors in Mice
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 furt
Slide 24: S.C. SIL204 PK Demonstrates Persistent Effective Exposure at Major Metastatic Site
S.C. SIL204 PK Demonstrates Persistent Effective Exposure at Major Metastatic Site Potential for durable efficacy of siRNA for treating micrometastases with monthly s.c. injections Plasma Kidney(left) Liver Skin • PK Studies in rats 10 mg/rat (~HED 400mg, 10000000 SIL204 Concentration (ng/mL) or (ng
Slide 25: S.C. SIL204 Demonstrates Positive Dose Response in Tumor Volume
S.C. SIL204 Demonstrates Positive Dose Response in Tumor Volume Responder analysis to SIL204 following SC injections in an orthotopic model . • Nude mice with orthotopic PANC-1 (KRAS G12D, luciferase) tumors showed dose-dependent tumor inhibition after subcutaneous (SC) SIL204 • Three different defi
Slide 26: Subcutaneous SIL204 Shrinks Distal Metastases in Animal Model
Subcutaneous SIL204 Shrinks Distal Metastases in Animal Model Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic Models Animal model represents human equivalent dose of SIL-204 • Reduction in bioluminescence indicates 6.00E+05 Bioluminescence decreased viable tumor burden
Slide 27: Late-Stage Clinical Development Roadmap for SIL204 in Pancreatic Cancer
Late-Stage Clinical Development Roadmap for SIL204 in Pancreatic Cancer Optimization of siRNA Toxicology: 2 species to • s.c. formulation stability Initiate Phase 2/3, to improve efficacy initiate clinical trial, in-life (initial) LAPC Germany/Israel and stability completed; Histology ongoing • GMP
Slide 28: Strong Intellectual Property Protection
Strong Intellectual Property Protection Submissions Filing – Term-claims Patents supporting SIL204 • Compositions for Inhibition of Kras Expression and • National phase submissions pending in: USA; EU; Japan; China; Brazil; India; Methods of Use Thereof. Australia; Canada; Korea; Israel from PCT (PC
Slide 29: Silexion Positioned to Develop the Most Advanced Oncogene Silencing Therapy
Silexion Positioned to Develop the Most Advanced Oncogene Silencing Therapy Instead of targeting mutated KRAS proteins after they are formed (as competing technologies KRAS-Focused RNA do) Silexion’s siRNA technology silences their expression at the outset, offering a potentially Interference Platfo
Slide 30: World-Renowned Expert Scientific Advisory Board
World-Renowned Expert Scientific Advisory Board Eileen M. O'Reilly, MD Thomas Seufferlein, MD Memorial Sloan Kettering, NY, NY University Hospital Ulm, German Winthrop Rockefeller Endowed Chair of Medical Oncology; Co- Director of Internal Medicine University Hospital Ulm, President Director, Medica
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 Ilan Hadar Chairman & Chief Executive Officer email: [email protected] Dr. Mitchell Shirvan Chief Scientific and Development Officer email: [email protected] Mirit Horenshtein-Hadar Chief Financial Officer email: [email protected] 32 Nasdaq: SLXN
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