Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (March 2025)
32 slides from Silexion Therapeutics's investor presentation, March 2025
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Silencing Oncogenes at the Level of Gene Expression Corporate Presentation March, 2025 Nasdaq: SLXN
Slide 2: Forward-Looking Statement
Forward-Looking Statement 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 strateg
Slide 3: Company Overview
Company Overview Clinical-stage company developing proprietary treatments for KRAS-driven cancers KRAS-Focused RNA Silexion’s siRNA platform technology is designed to silence oncogenes and prevent the production of the Interference Platform mutated KRAS proteins that drive cancer growth • First gene
Slide 4: KRAS Oncogene is a Validated Target for Numerous Cancers
KRAS Oncogene is a Validated Target for Numerous Cancers Prevalence of The Most Common Types of KRAS Mutations Across Cancers Small Bowel PDAC CRC Non-sq NSCLC Appendix Adenocarcinoma % KRAS mutations 92% 49% 35% 53% 61% KRAS is the most common oncogenic gene driver in human cancers with gastrointes
Slide 5: Pancreatic Cancer Has One of the Highest Mortality Rates of All Major Cancers
Pancreatic Cancer Has One of the Highest Mortality Rates of All Major Cancers Types and Prevalence of Pancreatic Cancer4,5 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 sur
Slide 6: Innovatively Treating the Cancer-Driving KRAS at the Source and Site of Action
Innovatively Treating the Cancer-Driving KRAS at the Source and Site of Action Functional Mutated Mutated Cancer mutated KRAS KRAS gene KRAS mRNA Progression protein Transcription Translation Cell proliferation Migration Transformation Survival Inhibits oncogenic protein mRNA destroyed, no oncogenic
Slide 7: Silexion Innovative Oncological Approach
Limitation of currently approved and investigational small molecule KRAS inhibitors: • Treatment resistance Silexion • Low tolerability with adverse events such as rashes and GI side effects that Innovative require special monitoring Oncological • Limited overall response rate and progression-free s
Slide 8: SIL204 is the Most Advanced siRNA Formulation for LAPC With a Significant Market Opportunity
SIL204 is the Most Advanced siRNA Formulation for LAPC With a Significant Market Opportunity KRAS mutations are present in ~92% pancreatic cancer cases1 SIL204 targets > 74% of KRAS mutations in PDAC2 Total Addressable Market in Localized Advanced while currently available KRAS G12C treatment Pancre
Slide 9: LODER (First generation siRNA) Phase 2 Clinical Trial Data
LODER (First generation siRNA) Phase 2 Clinical Trial Data
Slide 10: Phase 2 Trial of Loder Completed in 2023 – a Proof-of-Concept
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 Arm 1: LODER + SOC Chemo (n=18) Long-term follow up Key inclusion criteria Coho
Slide 11: Baseline Characteristics and Cohorts Information
Baseline Characteristics and Cohorts Information Cohort 1 Cohort 2 (n=29) (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
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 0.3 Best % change in tumor size 0.3 0.2 0.2 0.1 0.1 from baseline 0 0 -0.1 -0.1 -0.2 -0.2 -0.3 -0.3 -0.4 -0.4 -0.5 -0.5 -0.6 -0.6 -0.7 -0.7 Cohort 1 Cohort 1+2 Cohort 1 Cohort 1+2
Slide 13: Cohort 1 Patients Treated with Loder Had 9.3 Months Improvement in Overall Survival
Cohort 1 Patients Treated with Loder Had 9.3 Months Improvement in Overall Survival Overall Survival in Cohort 1 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 siRNA+SOC chemo mortality. median=22.7 mo. SOC chemo median =13.4 mo.* Patients
Slide 14: Phase 2 Safety Results
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) All grades Grades 3-4 SAE n (%) n (%) Gastrointestinal disorders 3 (8%) 2 (5%) Hematemesi
Slide 15: LODER Was Overall Well Tolerated
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
Slide 16: SIL204 siRNA: Enhanced Stability and Broadening Silencing Activity
• Enhanced stability siRNA: • Broadening silencing activity Optimizations allows for comprehensive approach: systemic and intratumor administrations Successful preclinical results in metastatic models with subcutaneous administration and primary tumor models with intratumor administration
Slide 17: Leveraging LODER Clinical Data to Further Improve SIL204 Potential Efficacy and Safety
Leveraging LODER Clinical Data to Further Improve SIL204 Potential Efficacy and Safety ` LODER SIL-204 siRNA target KRAS G12D/V+ KRAS amplify KRAS G12D/V+ KRAS amplify, potential pan KRAS Stability in human serum (HS) and HS > 48 hrs, Remains at substantial levels for >56 Days in plasma HS <1 hr rat
Slide 18: SIL204 Shows Broad Inhibition Across Human KRAS Mutations at Sub-Nanomolar Concentrations
SIL204 Shows 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. Negative WT KRAS K
Slide 19: SIL204 is Stable In Vitro for Over 48 Hours in Human Serum
SIL204 is Stable In Vitro for Over 48 Hours in Human Serum siRNA strand placed in human serum and tested for stability Stability of siRNA Strand in Human Serum LODER SIL-204 100% 90% Potentially longer effectiveness of siRNA 80% Greater ability to diffuse % OF INTACT SIRNA GUIDE STRAND 70% 60% throu
Slide 20: SIL204 Remains at Substantial Levels for >56 Days in Plasma and Tissues
SIL204 Remains at Substantial Levels for >56 Days in Plasma and Tissues Single subcutaneous administration SIL204 solution (10mg, not formulated) to Sprague Dawley rats 10000000 SIL204 Concentration (ng/mL) or (ng/g) Plasma Colon Kidney(left) Liver Lung Pancreas Skin 1000000 100000 Potential for lon
Slide 21: SIL204 Behaves Synergistically with Fluorouracil and Irinotecan-Containing Chemotherapy
SIL204 Behaves Synergistically with Fluorouracil and Irinotecan-Containing Chemotherapy 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 Panc1 cell confluence after 90 hrs Panc1 ce
Slide 22: Intratumor Administered SIL204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice
Intratumor Administered SIL204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice 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
Slide 23: Systemic Administration of siRNA Strongly Supported by Preclinical Data
Systemic Administration of siRNA Strongly Supported by Preclinical Data 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 140 Negative Con
Slide 24: Systemic Administration of siRNA Strongly Supported by Preclinical Data
Systemic Administration of siRNA Strongly Supported by Preclinical Data Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic Models Animal model represents the human equivalent dose of SIL-204 10000 Negative Control Bioluminescence Change (%) 8000 SIL204-Low Dose Low dosage
Slide 25: Systemic Administration of siRNA Strongly Supported by Preclinical Data
Systemic Administration of siRNA Strongly Supported by Preclinical Data Subcutaneous SIL204 Proved Effective in Mouse Metastatic Pancreatic Orthotopic Models Animal model represents human equivalent dose of SIL-204 3000 Bioluminescent imaging of metastatic organs Vehicle, s.c., QW x 4W, n=8 Control
Slide 26: SIL204 Development Strategy in LAPC
SIL204 Development Strategy in LAPC Optimization of siRNA • Initiate toxicology GMP production Initiate Phase 2/3, on various fronts; studies SIL-204 injectable formulation LAPC Germany/Israel selection of SIL-204 • GMP production API (SIL-204) 2023 2024 H1 2025 H2 2025 H1 2026 H2 2026 Clinical proo
Slide 27: 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 28: Strong Intellectual Property Protection
Strong Intellectual Property Protection Submissions Term 10 patents issued world-wide, 6 patients Patents supporting siG12DLoder pending. Protection until 2030 plus extension Patents supporting SIL204 PCT (PCT/ IL2023/051276). Expected protection • Inhibition of KRAS expression and methods of use th
Slide 29: 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 30: Highly Experienced Leadership Team
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, inn
Slide 31: Investment Highlights
Investment Highlights • Clinical-stage company with proprietary oncogene silencing siRNA platform Advanced RNA • Phase 2 clinical trial with first generation Loder in LAPC showed strong trend for 9.3 months improvement in therapeutic candidate in survival oncology • Second generation SIL204 with enh
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, CPA Chief Financial Officer email: [email protected] Nasdaq: SLXN
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