Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (February 2026)
32 slides from Silexion Therapeutics's investor presentation, February 2026
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Silencing Oncogenes at the Level of Gene Expression Company Presentation | February 2026 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: Transforming treatment in historically undruggable cancers
Transforming treatment in • Lead product targets the most common oncogenic driver in human cancers, mutated KRAS gene historically “undruggable” cancers by tackling the • Our technology, siRNA, isolates the oncogene, resulting in shutting down the cancer driving processes driver of poor outcomes Fir
Slide 4: Agenda
Agenda • Market and unmet need • Our technology • Advantages and differentiation of our technology / product • First generation siRNA Phase 2 clinical results and preclinical results SIL204 • SIL204 Phase 2/3 design • SIL204 development plan and milestones achieved • Patent protection for SIL204 4
Slide 5: Prevalent Cancers with KRAS Mutation we Target
Prevalent Cancers with KRAS Mutation we Target Pancreatic Ductal Colorectal Cancer Non-squamous Non- Adenocarcinoma (CRC) Small-Cell Lung Cancer (PDAC) (Non-sq NSCLC) % KRAS mutations1 92% 49% 35% Incidence USA+EU ~200K ~500K ~400K PDAC: 3rd leading cause cancer deaths today in the U.S.2, 2nd leadin
Slide 6: Types and Relative Prevalence of Pancreatic Cancer
Types and Relative Prevalence of Pancreatic Cancer Local Metastatic 15-25% ~50% ~30 Resectable Metastatic LAPC + BRPC ~75% liver BRPC=borderline resectable pancreatic cancer; LAPC = locally advanced pancreatic cancer. 6 Gemenetzis G, et al. Ann Surg. 2019;270(2):340-347; Kleeff J, et al. Nat Rev Dis
Slide 7: Unmet Needs in Pancreatic Cancer (PC)
Unmet Needs in Pancreatic Cancer (PC) • Overall 5-year survival one of poorest U.S 12.8% 1 , KRAS G12D/V worst survival • Resectable PC- Following surgery with perioperative chemotherapy, ~80% have metastases in 1 yr 2 • Median survival LAPC 14-17mo.3,4 • New small molecule RAS inhibitors efficacy p
Slide 8: Our Technology
Our Technology • Lead Product: SIL204 • First-in-class, isoform selective, pan KRAS silencer, stable siRNA with targeted delivery system • Targets both the active and inactive forms of KRAS x 8
Slide 9: Dual Administration of SIL204 Designed to Treat Primary Tumor and Metastases
Dual Administration of SIL204 Designed to Effectively Treat the Two Distinct Processes of the Disease: Primary Tumor and Metastases Systemic (s.c.) SIL204 Targets cancer cells shedding from primary tumor with metastatic invasions into liver, etc. Intratumoral (endoscopic) SIL204 Targets Primary panc
Slide 10: Our Technology
Our Technology • SIL204 binds to LDLs to high extent and carries the SIL204 systemically • Pancreatic cancer cells have significantly higher LDL receptors than health pancreatic cells • Enriched uptake by cancer cells compared to healthy • Difference even more significant in metastatic pancreatic ce
Slide 11: Advantages and Differentiation
Advantages and Differentiation Integrated Dosing Targeting both primary tumor and micrometastases Safety Specificity Efficacy (For KRAS, not RAS Pan-KRAS No off-target binding) Works upstream prior to LDL targeting KRAS production Not oral route Competitive SIL204 positioned to become the most advan
Slide 12: LODER (First generation siRNA) Phase Clinical Trial Data
Results LODER (First generation siRNA) Phase 2 Clinical Trial Data
Slide 13: First-Generation Loder Led to Robust RECIST Antitumor Activity
First-Generation Mutant KRAS RNA Silencer (Loder) Led to Robust RECIST* Antitumor Activity in mutant KRAS-Driven Locally Advanced Pancreatic Cancer 0.5 0.4 Reduction in tumor size: Cohorts 1+2 0.3 Best % change in tumor size from 0.2 KRAS mutation subtype G12D G12V 0.1 Chemo 0 Loder baseline -0.1 R
Slide 14: SIL204 Second Generation
Results SIL204 Second Generation
Slide 15: SIL204 Knockdown of mRNA Transcript and KRAS Protein
SIL204 Knockdown of mRNA Transcript and Corresponding KRAS Protein mRNA 1 KRAS Protein 1 KRAS/GAPDHNormalized fold Normalized fold (2-∆∆Ct) 0.8 0.8 0.6 0.6 **** **** 0.4 0.4 0.2 0.2 0 0 control 5 nM 50 nM control 5nM 50nM Transfection with lipofectamine PK59 human tumor line G12D mutation 15 Analysi
Slide 16: SIL204 (Second Generation siRNA)
SIL204 (Second Generation siRNA)
Slide 17: 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 first generation siG12DLoder Model is a co-transfection setup where human KRAS is transfected in mouse Hepa1-6 cells with Dual-Glo reporter
Slide 18: SIL204 Inhibits Growth of Human Tumor Cell Lines
SIL204 Inhibits Growth Human Tumor Cell Lines from Various Cancers with G12x and Q61x Mutations Cell line IC50 (ng/mL) IC90 (nM) IC90 (ng/mL) KRAS mutation subtype A427 (Lung) 537 70 1,079 G12D PK59 (Panc) 1,059 163 2,496 G12D GP2D (Colon) 445 56 852 G12D HS766T (Panc) 476 124 1,907 Q61H AVG 613 103
Slide 19: In Silico Stability Shows High Specificity of SIL204 for KRAS
In Silico Thermodynamic Stability of Potential Duplexes Shows High Specificity of SIL204 for (K)RAS and Not (H)RAS/(N)RAS and No Off-target Binding Conclusions • SIL204 binding to KRAS G12V strong (-31.8 kcal/mole) • SIL-204 will silence the intended target KRAS mutations, but low risk for any effec
Slide 20: Intratumor SIL204 Reduced Tumor Volume in Pancreatic Cancer Xenograft
Intratumor SIL204 Significantly Reduced Tumor Volume and Growth While Increasing Tumor Necrosis (cell death) in Human Pancreatic Cancer Xenograft Day 1: Capan-1 (KRAS G12V) luciferase cells were xenografted to mice (s.c.) concurrently with SIL204 formulated in extended-release microparticles Day 15:
Slide 21: SIL204 Remains at Substantial Levels for >56 Days in Rats
SIL204 Remains at Substantial Levels for >56 Days in Target Tissues in Rats Potential for treating micrometastases with clinical s.c. dosing on monthly basis Plasma Kidney(left) Liver Skin 10,000,000 SIL204 Concentration (ng/mL) or (ng/g) 1,000,000 100,000 10,000 IC90 1,000 IC50 100 10 1 0 7 14 21 2
Slide 22: Subcutaneous SIL204 in Orthotopic Metastatic Pancreatic Mouse Model
Subcutaneous SIL204 in Orthotopic Metastatic Pancreatic Mouse Model Bioluminescent imaging of Responder analysis metastatic organs 6.00E+05 Control Bioluminescence High dose SIL204 4.00E+05 (%) 2.00E+05 * 0.00E+00 intestine liver stomach spleen Human equivalent ~ mid-dose for trial 22 • Tumors from
Slide 23: SIL204 Anti-Tumor Activity Synergistic with Chemotherapy
SIL204’s Anti-Tumor Activity Synergistic with Pancreatic Cancer Chemotherapy Panc1 cell confluence after 67 hrs 45 *** * Cell Confluence 35 25 15 Untreated FOLFIRI 50µM FOLFIRI 50µM+SIL-204 * p<0.05, ***p<0.0005 23 Human pancreatic cell line Panc-1 (G12D)
Slide 24: Toxicology
Toxicology Favorable Tolerability with No Systemic Toxicity or Organ Damage • Extended single-dose GLP toxicity studies completed in 2 relevant species, aligned with ICH S9 guidance for oncology and confirmed by regulatory agency for initiation of Phase 2/3 clinical trial • Established safety margin
Slide 25: SIL204 Phase 2/3 Clinical Trial
SIl204 Phase 2/3 Clinical Trial SIL204 administered intratumorally and systemically as an integrated treatment regimen (IR) Primary endpoint: Overall survival (OS) Secondary endpoints: Progression-free survival (PFS), overall response rate (ORR), QoL Segment 1: Phase 2/3 safety run-in Initiation Q2
Slide 26: SIL204 Phase 2/3 Development Plan and Milestones Achieved
SIl204 Phase 2/3 Development Plan and Milestones Achieved • GMP API for Segment 1 manufactured, Segment 2 GMP manufacturing ongoing • GMP formulation selected, manufacturing in process • Toxicology for Segment 1 completed, for Segment 2/3 later in 2026 • Scientific Advice from national European auth
Slide 27: Strategic Collaboration for SIL204 GMP Clinical Supply
Strategic Collaboration for SIL204 GMP Clinical Supply with Leading European Manufacturers Collaboration to leverage Catalent and Axolabs’ experience in formulation development and manufacturing biologicals to further enhance SIL204's therapeutic potential through improved stability, bioavailability
Slide 28: Intellectual Property Protection
Intellectual Property Protection Submissions Term Entered national Phase world wide, SIL-204 as a composition and for use Expected protection until 2043 plus estimated in treatment of pancreatic and other cancers extension to 2048 (following successful USPTO review of PCT) U.S. Patent Application No
Slide 29: 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 (“PRFX”), CFO Foamix Pharmaceuticals Inc. (Currently “VYNE”) Mitchell Shirv
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: SIL204 First in class siRNA targeting KRAS mutation
SIL204 • Phase 2/3 initiation for locally advance pancreatic cancer to be initiated Q2/2026 First in class siRNA targeting KRAS mutation • Isoform selective, pan KRAS silencer, stable siRNA with targeted delivery system • Pipeline for additional cancers including CRC First generation (Loder) showed
Slide 32: Thank You
Thank You 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 Nasdaq: SLXN
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