Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (November 2024)
33 slides from Silexion Therapeutics's investor presentation, Nov 27, 2024
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Silencing Oncogenes at the Level of Gene Expression Nasdaq: SLXN Corporate Presentation December 2024
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: Company Overview
Company Overview Silexion’s siRNA platform technology is designed to silence oncogenes and prevent the production of the mutated KRAS proteins that drive cancer growth Loder siRNA with an extended release PLGA delivery system Completed Phase 2 trial Results observed a 9.3 months improvement in overa
Slide 4: KRAS Oncogene is a Validated Target for Numerous Cancers
KRAS Oncogene is a Validated Target for Numerous Cancers 4 Prevalence of The Most Common Types of KRAS Mutations Across Cancers CRC=colorectal cancer; LAPC=locally advanced pancreatic cancer; NSCLC=non-small cell lung cancer. Lee, J.K. et al. NPJ Precis Oncol. 2022;6(1):91. PDAC CRC Non-sq NSCLC Sma
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 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 Fac
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 Moving closer to treating the mechanism of the cancer more efficiently and with a greater chance to overcome treatment-resistance Cell proliferation Migration Transformation Survival Silexion siRNA Intratumor delivery KRA
Slide 7: Silexion Innovative Oncological Approach May Lead to Significant Improvement Over KRAS Inhibitors
Silexion Innovative Oncological Approach May Lead to Significant Improvement in Clinical Outcomes Over KRAS Inhibitors Treatment resistance Low tolerability with adverse events such as rashes and GI side effects that require special monitoring Limited overall response rate and progression-free survi
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 LAPC = localized advanced pancreatic cancer; ROW=rest of the world. *Number of KRAS G12D/V mutated LAPC were calculated based on KRAS mutations be
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 SoC=standard of care. Arm 1: LODER + SOC Chemo (n=18) Day 0 Randomization Long-
Slide 11: Baseline Characteristics and Cohorts Information
Baseline Characteristics and Cohorts Information Due to results of a clinical trial indicating FOLFIRINOX’s advantage over GnP as SoC chemotherapy, cohort 2’s SoC chemotherapy was changed from GnP (used in cohort 1) to FOLFIRINOX. BRPC=borderline resectable pancreatic cancer; GnP=gemcitabine/nab-pac
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* 12 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
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* 13 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
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 14 * 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) Time to death is slower, 41% reduction in the ra
Slide 15: Phase 2 Safety Results: Serious Adverse Events
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) SAE All grades n (%) Grades 3-4 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 (TEAE
Slide 17: Building upon the Loder results, we optimized
Building upon the Loder results, we optimized: siRNA: Formulation for better delivery Enhanced stability Broadening activity
Slide 18: SIL-204 KRAS G12D/V and KRAS amplification siRNA formulation
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 HR=Hazard Ratio. *EUS endoscopy is a standard procedure used to obtain ultrasound guided biopsies once every 3 months. ` LODER SIL-204 siRNA target KRAS G12D/V+ KRAS amplify KRAS G12D/V+ KRAS amplify, potential p
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 Potentially longer effectiveness of siRNA Greater ability to diffuse throughout the fibrous tumor environment Potential in other indication
Slide 21: Stability Studies Suggest SIL-204 is Considerably More Stable than Marketed siRNAs
Stability Studies Suggest SIL-204 is Considerably More Stable than all the siRNAs on the Market 21 1. Givlaari (givorisan). EMA. 2. Alnylam. Givosiran NDA MULTI-DISCIPLINE REVIEW. 3. Lumasiran. Review (fda.gov). 4. Lumasiran. Leqvio, INN-inclisiran (europa.eu) . 5. Inclisiran. Leqvio, INN-inclisiran
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 22 Model is a co-transfection setup in mouse Hepa1-6 cells with Dual-Glo reporter plasmids. Mutation NegativesiRNAControl WT KRAS KRAS G12D KRA
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 23 UT=untreated.
Slide 24: SIL-204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice
SIL-204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice ***p<0.0005 S.C. = sub cutaneous. 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 w
Slide 25: SIL204-MP Inhibited Human Pancreatic Cancer Xenograft Growth in Mice
SIL204-MP Inhibited Human Pancreatic Cancer Xenograft Growth in Mice SIL204-MP = microparticle formulated SIL-204. 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
Slide 26: SIL-204 Behaves Synergistically with Fluorouracil and Irinotecan-Containing Chemotherapy
SIL-204 Behaves Synergistically with Fluorouracil and Irinotecan-Containing Chemotherapy *p<0.05; ** p<0.005; ***p<0.0005 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
Slide 27: SIL-204 Development Strategy in LAPC
SIL-204 Development Strategy in LAPC 2023 2024 H1 2025 H2 2025 H1 2026 H2 2026 Clinical proof of concept for Loder in LAPC in an approvable endpoint for FDA Optimization of siRNA on various fronts; selection of SIL-204 with new extended-release formulation Received guidance on trial design from the
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 Arm 1: SIL-204B + SOC Chemo Arm 2: SOC Chemo End of Study Day 1, 2:1 Randomization DSMB ~15 subjects for safety following 1 mo. FU If pancreatectomy Post Surgery FU Tre
Slide 29: Focused Pipeline to Address KRAS-driven Solid Tumor Localized Cancers
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 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 > 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 CTA=clinical trial application; IND=investigational new drug. Clinical-stage company with proprietary oncogene siRNA platform Intratumor siRNA delivery for pancreatic cancer allow for better drug exposure compared with systemic KRAS inhibitors Phase 2 clinical trial with Loder
Slide 33: 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, CPA Chief Financial Officer email: mirit@silexion.com
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