Silexion Therapeutics Corp · NASDAQ:SLXN
Silexion Therapeutics — Investor Presentation (September 2024)
30 slides from Silexion Therapeutics's investor presentation, Sep 9, 2024
Slide 1: Silencing Oncogenes at the Level of Gene Expression
Sile ncing Oncogenes at the Level of Gene Expression Nasdaq: SLXN Corporate Presentation September 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 fut
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
Slide 4: Focused Pipeline to Address KRAS-driven Solid Tumor Localized Cancers
Status/ Anticipated Milestone Phase 3 Phase 2 Phase 1 Preclinical Discovery Setting Indication Program Phase 2 completed: observed 9.3 months improvement with LODER over SOC. Continue development of SIL - 204. Adjunct to chemotherapy Locally advanced pancreatic cancer LODER siG12D + KRAS amplify wit
Slide 5: KRAS Oncogene is a Validated Target for Numerous Cancers
KRAS Oncogene is a Validated Target for Numerous Cancers 5 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
Slide 6: 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
Slide 7: Treating KRAS the Cancer-Driver at the Source and Site of Action
Treating KRAS the Cancer - Driver at the Source and Site of Action Silexion siRNA technology prevents mutated KRAS from being produced while small molecule inhibitors target the functioning KRAS protein Silencing oncogene at the production stage is potentially more efficient and safe approach to tre
Slide 8: Silexion Innovative Oncological Approach vs KRAS Inhibitors
Silexion Innovative Oncological Approach May Lead to Significant Improvement in Clinical Outcomes Over KRAS Inhibitors • Treatment resistance • Requires special monitoring for GI adverse reactions • Limited overall response rate and progression - free survival • Low tolerability with adverse events
Slide 9: SIL-204 is the Most Advanced siRNA Formulation for LAPC
G12D G12V G12C G12A G12R Multiple Other KRAS SIL - 204 is the Most Advanced siRNA Formulation for LAPC With a Significant Market Opportunity KRAS mutations are present in ~92% pancreatic cancer cases 1 LAPC = localized advanced pancreatic cancer; ROW=rest of the world.*Number of KRAS G12D/V mutated
Slide 10: LODER Phase 2 Trial Data
LODER Phase 2 Trial Data Silexion
Slide 11: 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 Randomizati
Slide 12: 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. *KRAS mutations were determined in 31 patients in total. In cohort 1,
Slide 13: Loder Treatment Led to Robust Objective Response Rate in Cohort 1
-0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 Best % change in tumor size from baseline Loder Treatment Led to Robust Objective Response Rate in Cohort 1 Patients with LAPC Harboring G12D/V Mutations* 13 LAPC=locally advanced pancreatic cancer *Overall response rate was confirmed by RECIS
Slide 14: 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* 14 -0.7 -0.6 -0.5 -0.4 -0.3 -0.2 -0.1 0 0.1 0.2 0.3 0.4 0.5 Best % change in tumor size from baseline LAPC=locally advanced pancreatic cancer *Overall response rate was confirmed by REC
Slide 15: 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 15 * 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 th
Slide 16: 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) Grades 3 - 4 n (%) All grades n (%) SAE 2 (5%) 3 (8%) Gastrointestinal disorders 0 (0
Slide 17: Loder Was Overall Well Tolerated
Loder Was Overall Well Tolerated • The Phase 2 PoC c linical 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 • N o Treatment Emergent Adverse Ev
Slide 18: Building upon the Loder results, we optimized
Building upon the Loder results, we optimized: siRNA : Formulation for better delivery • Enhanced stability • Broadening activity
Slide 19: SIL-204: KRAS G12D/V and KRAS amplification siRNA formulation
SIL - 204 KRAS G12D/V and KRAS amplification siRNA formulation
Slide 20: Leveraging Loder Clinical Data to Further Improve SIL-204
Leveraging Loder Clinical Data to Further Improve SIL - 204 Potential Efficacy and Safety *EUS endoscopy is a standard procedure used to obtain ultrasound guided biopsies once every 3 months . SIL - 204 LODER ` KRAS G12D/V+ KRAS amplify, potential pan KRAS KRAS G12D/V+ KRAS amplify siRNA target > 48
Slide 21: SIL-204 is Stable In Vivo in Rats for Five Hours
SIL - 204 is Stable In Vivo in Rats for Five Hours 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 ( europa.eu ). 6. Inclisira
Slide 22: 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 indicati
Slide 23: SIL-204 Robustly Inhibited the Various Human KRAS Mutations at Sub-nM Conc.
SIL - 204 Robustly Inhibited the Various Human KRAS Mutations at Sub - nM Conc. SIL - 204 maintains and expands the silencing activity of the Loder 23 Maximum Silencing (%) of KRAS G12x Mutations / IC 50 ( nM ) External ID G13D* G12R G12C G12V G12D Non - mutated 88 0.37 70 0.59 73 0.47 80 0.44 90 0.
Slide 24: SIL-204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice
SIL - 204 Inhibited Human Pancreatic Cancer Xenograft Growth in Mice * p<0.05; ** p<0.005; ***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 t
Slide 25: SIL-204 Development Strategy in LAPC
SIL - 204 Development Strategy in LAPC 2023 H1 2024 H 1 2025 H2 2025 H 1 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 desig
Slide 26: 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 Surg
Slide 27: 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
Slide 28: 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,
Slide 29: 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 wit
Slide 30: Thank You
Thank You Nasdaq: SLXN Ilan Hadar Chief Executive Officer email: i hadar@silexion.com mobile: 972 - 54 - 5331725 Dr. Mitchell Shirvan Chief Scientific and Development Officer email: m shirvan@silexion.com mobile: 972 - 52 - 725 - 6667
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