Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (December 2024)
33 slides from Silexion Therapeutics's investor presentation, December 2024
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Silencing Oncogenes at the Level of Gene Expression Corporate Presentation December 2024 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 with mutated KRAS proteins that drive cancer growth Targete
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 Mutated Functional Mutated Cancer KRAS gene mutated KRAS 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: SIL-204 is the Most Advanced siRNA Formulation for LAPC With a Significant Market Opportunity
SIL-204 is the Most Advanced siRNA Formulation for LAPC With a Significant Market Opportunity KRAS mutations are present in ~92% pancreatic cancer cases1 SIL-204 covers > 74% of KRAS mutations in PDAC2 Total Addressable Market in LAPC while currently available KRAS G12C treatment are treating ~1.5%
Slide 9: LODER Phase 2 Trial Data
LODER Phase 2 Trial Data Silexion
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 Cohort 1
Loder Treatment Led to Robust Objective Response Rate in Cohort 1 Patients with LAPC Harboring G12D/V Mutations* 0.5 0.4 Best % change in tumor size 0.3 0.2 from baseline 0.1 0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 G12D G12V LODER+Chemo Chemo Chemo: % Response 55 (6/11) 20 (1/5) Loder: R = Non-resectab
Slide 13: Loder Treatment Led to Robust Objective Response Rate in Cohort 1+2
Loder Treatment Led to Robust Objective Response Rate in Cohort 1+2 Patients with LAPC Harboring G12D/V Mutations* 0.5 0.4 Best % change in tumor size 0.3 0.2 from baseline 0.1 0 -0.1 -0.2 -0.3 -0.4 -0.5 -0.6 -0.7 G12D G12V LODER+Chemo Chemo Chemo: % Response 56 (10/18) 20 (1/5) Loder: R = Non-resec
Slide 14: 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 15: 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 16: 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 17: Building upon Loder results, we optimized formulation and siRNA
Formulation for better delivery • Enhanced stability siRNA: • Broadening activity Building upon the Loder results, we optimized:
Slide 18: SIL-204
SIL-204 KRAS G12D/V and KRAS amplification siRNA formulation
Slide 19: Leveraging Loder Clinical Data to Further Improve SIL-204 Potential Efficacy and Safety
Leveraging Loder Clinical Data to Further Improve SIL-204 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 <1 hr > 48 hrs Access to tumor cell site of action No hydrophobic lead Added hydrophob
Slide 20: SIL-204 is Stable In Vitro for Over 48 Hours in Human Serum
SIL-204 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% thro
Slide 21: Stability Studies Suggest SIL-204 is Considerably More Stable than all the siRNAs on the Market
Stability Studies Suggest SIL-204 is Considerably More Stable than all the siRNAs on the Market siRNA Half-Life in Rats and Human Plasma (not a head-to-head comparison) Rat Human 10 9 8 7 6 Hour 5 4 3 2 1 0 SIL-204 Givosiran Lumasiran Inclisiran Vutrisiran SIRNA Greater ability to diffuse throughout
Slide 22: SIL-204 Shows Broad Inhibition Across Human KRAS Mutations at Sub-Nanomolar Concentrations
SIL-204 Shows Broad Inhibition Across Human KRAS Mutations at Sub-Nanomolar Concentrations SIL-204 maintains and expands the silencing activity of the Loder Model is a co-transfection setup in mouse Hepa1-6 cells with Dual-Glo reporter plasmids. Negative WT KRAS KRAS KRAS KRAS KRAS KRAS Mutation siR
Slide 23: SIL-204 Robustly Inhibits Growth of Human Pancreatic Tumor Cell Line (Panc-1)
SIL-204 Robustly Inhibits Growth of Human Pancreatic Tumor Cell Line (Panc-1) in Dose-Dependent Manner Panc1+SIL-204 30 UT change in cell confluence, % SIL-204 100 µg/ml 25 SIL-204 50 µg/ml SIL-204 25 µg/ml 20 SIL-204 12.5 µg/ml SIL-204 6.25 µg/ml 15 10 5 0 0 10 20 30 40 50 60 70 80 90 100 hrs 23 UT
Slide 24: SIL-204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice
SIL-204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice SIL-204 significantly reduced tumor volume and growth while increasing the necrosis (cell death) within the tumor Day 1: Capan-1 (G12V) luciferase cells were xenografted to mice (s.c.) concurrently with SIL-204 formulated in extended
Slide 25: SIL204-MP Inhibited Human Pancreatic Cancer Xenograft Growth in Mice
SIL204-MP Inhibited Human Pancreatic Cancer Xenograft Growth in Mice SIL-204 significantly reduced tumor area and increased tumor necrosis ~Day -7: Panc-1(G12D mutation) cells were xenografted to mice (s.c.) and grown to ~200mm3 Day 1: SIL-204-MPs or PBS (phosphate buffer Saline) was injected sub-cu
Slide 26: SIL-204 Behaves Synergistically with Fluorouracil and Irinotecan-Containing Chemotherapy
SIL-204 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 26 *p<0.05; ** p<0.005; ***p<0.0005
Slide 27: SIL-204 Development Strategy in LAPC
SIL-204 Development Strategy in LAPC Optimization of siRNA • Initiate toxicology • GMP production MP Initiate Phase 2/3, on various fronts; studies SIL-204 formulation LAPC Germany/Israel selection of SIL-204 • GMP production API with new extended- (SIL-204) release formulation • GMP production inje
Slide 28: Phase 2/3 Trial of SIL-204 in LAPC: Study Design
Phase 2/3 Trial of SIL-204 in LAPC: Study Design Received positive guidance from German regulatory agency on suggested trial design Phase 2 Safety Phase 2 Chemo run-in Phase 3 run-in expanded Arm 1: SIL-204B + SOC Chemo Post Surgery FU Chemo run-in Treatment If pancreatectomy Death 28d Arm 2: SOC Ch
Slide 29: 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 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 > 25 years of multinational managerial and corporate experience with pharmaceutical and high-tech companies Mitchell Shirvan, PhD, MBA Chief Scientific and Development Officer > 25 years of experience in R&D, inn
Slide 32: Investment Highlights
Investment Highlights • Clinical-stage company with proprietary oncogene siRNA platform Advanced RNA • Intratumor siRNA delivery for pancreatic cancer allow for better drug exposure compared with systemic KRAS therapeutic candidate in inhibitors oncology • Phase 2 clinical trial with Loder in LAPC s
Slide 33: 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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