Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (October 2022)
36 slides from Silence Therapeutics's investor presentation, October 2022
Slide 1: Silence Therapeutics
Silence Therapeutics October 2022
Slide 2: Forward-Looking Statements
Forward-Looking Statements The information contained in this presentation is being supplied and communicated to you solely for your information and may not be reproduced, further distributed to any other person or published, in whole or in part, for any purpose. The distribution of this presentation
Slide 3: Silence Vision and Strategy
Silence VISION and STRATEGY VISION STRATEGY Transform peoples’ lives around the world by Maximize our proprietary silencing diseases through our precision mRNAi GOLD™ platform through engineered medicines and driving positive change for the communities around us. hybrid business model 3
Slide 4: Silence is a Leader in siRNA Poised for Transformation
Silence is a Leader in siRNA Poised for Transformation • Two decades of know-how combined with robust and growing IP estate Pioneers in RNAi • Global footprint – HQ in London, R&D in Berlin and Hoboken, NJ office 1 • SLN360 (Cardiovascular Disease) - positive data in phase 1 study in healthy volunte
Slide 5: Executive Leadership Team with Deep Sector Experience
Executive Leadership Team with Deep Sector Experience Craig Tooman Dr. Giles Campion President and CEO EVP, Head of R&D and CMO • 30+ years of experience in the biopharmaceutical industry • 30+ years of experience in the biopharmaceutical industry • Previously CEO at Aratana Therapeutics where he •
Slide 6: siRNA Can Inhibit Expression of Disease-Associated Genes
siRNA Can Inhibit Expression of Disease-Associated Genes nucleus HEALTHY DISEASE Genes encode In certain diseases messages for the DNA is mutated all features in or abnormally the body expressed cytoplasm DNA The information in DNA is Abnormal DNA message is transcribed into messenger RNA mRNA carri
Slide 7: siRNA Can Precisely Target and Silence Disease-Associated Genes
siRNA Can Precisely Target and Silence Disease-Associated Genes Mutated DNA Natural mRNA Harnesses natural cellular Target-specific short interfering mechanisms present in every cell in RNA (siRNA) binds to the mRNA the human body mRNA is degraded and Durable gene is “silenced” Long-lasting gene kno
Slide 8: The Difference Between Gene Silencing, Gene Therapy and Gene Editing
The Difference Between Gene Silencing, Gene Therapy and Gene Editing GENE SILENCING GENE THERAPY GENE EDITING Prevents expression of a disease-related Compensates for a disease-related gene by Corrects a disease-related gene by gene by targeting the mRNA it produces delivering a functional copy of i
Slide 9: Our Toolbox Considers all Elements of siRNA and Ligand Design
Our Toolbox Considers all Elements of siRNA and Ligand Design siRNA molecule Linker GalNAc Ligand (delivery tool) • siRNA matched to target gene • Silence has developed • GalNAc ligand delivers proprietary linkers, enabling molecule to specific liver • Silence has developed chemical the attachment o
Slide 10: Platform Approach: Precision-Engineered Therapies
Platform Approach: Precision-Engineered Therapies alNAc igonucleotide iscovery Platform Designed to: Improve molecular design Maximize efficacy Minimize off-target effects High-quality discovery Stabilize molecules programs Optimize manufacturing Robust and growing IP estate 10
Slide 11: Early-stage GalNAc-conjugated RNAi Programs Have a Much Greater Likelihood of Approval
Early-stage GalNAc-conjugated RNAi Programs Have a Much Greater Likelihood of Approval vs. Industry Average Likelihood of Approval from Current Phase: GalNAc RNAi vs. others 100% 80% 67% GalNAc-conjugated 56% RNAi 60% 51% 53% Pharma industry 40% average (excluding GalNAc- 17% conjugated RNAi) 20% 9%
Slide 12: Partnership Programs Provide ~$7.5 Billion in Potential Milestones Plus Royalties
Partnership Programs Further Expand Pipeline and Provide ~$7.5 Billion in Potential Milestones Plus Royalties Signed deal to discover, develop and commercialize siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases in March 2020 • Upfront cash payment of $60 million and an
Slide 13: Pipeline Balances Proprietary & Partnered Programs
Pipeline Balances Proprietary & Partnered Programs Indication Target Discovery Preclinical Phase I Phase II Phase III Proprietary/Partnered Cardiovascular SLN360 disease due to high Lp(a) Lp(a) Beta Thalassemia SLN124 TMPRSS6 Polycythemia Vera (PV) Multiple Programs Undisclosed Undisclosed SLN-HAN-1
Slide 14: Clinical Programs
Clinical Programs 14
Slide 15: Positive Clinical Data Shown in Two mRNAi GOLD Platform Programs
Positive Clinical Data Shown in Two mRNAi GOLD™ Platform Programs Targeting Common and Rare Diseases Target Ph 1 Study Efficacy Durability Safety / Tolerability 32 healthy Effects persisting at Lp(a) reductions Well tolerated with no LPA volunteers 150 days – longer SLN360 observed up to 98% clinica
Slide 16: SLN360: Cardiovascular Disease
SLN360 Cardiovascular Disease 16
Slide 17: SLN360 Targets Lp(a): an Independent Risk Factor for Cardiovascular Disease
SLN360 Targets Lp(a): an Independent Risk Factor for Cardiovascular Disease Lp(a) levels are genetically determined Recognized as a major untreated risk factor in cardiovascular disease Lp(a) levels are not significantly modifiable by approved medicines or lifestyle changes Large population worldwid
Slide 18: Cardiovascular Event Risk Significantly Increases with High Lp(a)
Cardiovascular Event Risk Significantly Increases with High Lp(a) Substantial Risk of CV Event at Lp(a) ~90 mg/dL 780 Million Worldwide with >90 mg/dL Lp(a) Event Increased Risk Heart Attack1 2 - 3x Lp(a) level: >50 mg/dL >90 mg/dL Prevalence6 ~20% ~10% Aortic Stenosis2 2 - 3x USA 66m 33m EU 103m 51
Slide 19: SLN360 Has Substantial Market Potential
SLN360 Has Substantial Market Potential High Cholesterol vs High Lp(a) in Cardiovascular Disease High Cholesterol is a Modifiable Risk Factor • Some patients require cholesterol lowering treatment: Lifestyle changes can have a positive impact High Lp(a) is a Genetic Risk Factor • Most patients will
Slide 20: SLN360 Phase 1 Program Overview
SLN360 Phase 1 Program Overview Global randomized, double-blind, placebo controlled Design single dose and multiple dose study Investigate the safety, tolerability, PK and PD response Aim of SLN360 s.c. dosing in subjects with high Lp(a) ≥ 150 nmol/L • Enrolled 32 healthy adults with high Lp(a) Sing
Slide 21: SLN360 Lowered Lp(a) Up to 98% After a Single Dose
SLN360 Lowered Lp(a) Up to 98% After a Single Dose in Phase 1 Study in Healthy Adults with High Lp(a) 0% -10% Lipoprotein(a) Change (%) -20% -30% -40% -50% 70% 96% reduction -60% reduction -70% 98% -80% reduction -90% 81% reduction -100% Baseline Day 7 Day 14 Day 30 Day 45 Day 60 Day 90 Day 150 Plac
Slide 22: SLN360 Demonstrated Positive Results in Phase 1 Study
SLN360 Demonstrated Positive Results in Phase 1 Study in Healthy Adults with High Lp(a) EFFICACY SLN360 lowered Lp(a) up to 98% after a single dose DURABILITY >70% and >80% reductions in Lp(a) persisted for 150 days after the 300 mg and 600 mg doses SAFETY Well tolerated with no major safety issues
Slide 23: Results Presented at ACC and Published in JAMA
Results Simultaneously Presented in a Late Breaker at the ACC Annual Meeting and Published in JAMA in April 2022 We thought it would work, but we were surprised by the magnitude and the duration of the effect. Lipoprotein(a) is the last frontier in lipids... Steven E. Nissen, M.D., Chief Academic Of
Slide 24: SLN360 Phase 2 Study Overview
SLN360 Phase 2 Study Overview Design Multi-center, randomized, double-blind, placebo-controlled, phase 2 study Investigate the efficacy, safety and tolerability of SLN360 s.c. dosing in subjects with Aim high Lp(a) ≥ 125 nmol/L at high risk of ASCVD events Enrollment ~160 participants Dosing 3 SLN36
Slide 25: SLN124: Hematological Disorders
SLN124 Hematological Disorders 25
Slide 26: SLN124 Has Potential for Broad Mechanistic Mode of Action Approach
26 SLN124 Has Potential for Broad Mechanistic Mode of Action Approach SLN124 targets Positive preclinical data Proof of mechanism TMPRSS6 and controls showing therapeutic demonstrated in hepcidin – the body’s potential in several healthy volunteer master iron regulator hematological disorders study
Slide 27: SLN124 is Designed to Restore Endogenous Hepcidin and Normalize Iron Levels
SLN124 is Designed to Restore Endogenous Hepcidin and Normalize Iron Levels Reduced Raised Lowered systemic Improved 1 TMPRSS6 2 endogenous 3 iron levels and 4 red blood cell in the liver hepcidin normalizes production distribution + 2.5 g/dL 1.5 600 60 Serum Hepcidin [ng/ml] TMPRSS6/Actin mRNA ***
Slide 28: SLN124 Proof of Mechanism Established in Healthy Volunteer Study
SLN124 Proof of Mechanism Established in Healthy Volunteer Study SLN124 increased average hepcidin up to ~4-fold and EFFICACY reduced serum iron ~50% after a single dose DURABILITY Activity persisted for at least 2 months (study period) SAFETY Well tolerated with no serious or severe treatment emerg
Slide 29: SLN124 Increased Average Hepcidin up to ~4-Fold
SLN124 Increased Average Hepcidin up to ~4-Fold After a Single Dose with Activity Sustained for ≥ 2 Months 12 3.9x 10 Hepcidin (nmol), mean and fold increase 3.3x 8 2.3x 6 2.4x 2.1x 2.2x 4 2 0 Placebo SLN124 1.0 mg/kg SLN124 3.0 mg/kg SLN124 4.5 mg/kg n=6 healthy volunteers in each treatment group B
Slide 30: SLN124 Reduced Serum Iron by ~50%
SLN124 Reduced Serum Iron by ~50% After a Single Dose with Activity Sustained for ≥ 2 Months 25 20 Iron (µmol/L), mean and % change 15 -22% -24% -42% -16% 10 -47% -48% 5 0 Placebo SLN124 1.0 mg/kg SLN124 3.0 mg/kg SLN124 4.5 mg/kg n=6 healthy volunteers in each treatment group Baseline Day 29 Day 57
Slide 31: SLN124 Phase 1 Program in Adult Thalassemia
SLN124 Phase 1 Program in Adult Thalassemia Global, randomized, single-blind, placebo controlled Design single dose and multiple dose study Investigate the safety, tolerability, PK and PD response Aim of SLN124 s.c. dosing in adults with NTD thalassemia Enrollment ~ 24 adults with NTD thalassemia Do
Slide 32: Preliminary Single Dose Results from SLN124 Phase 1 Study in Thalassemia
Preliminary Single Dose Results from SLN124 Phase 1 Study in Thalassemia Patients • No serious adverse events, severe TEAEs that were SLN124 related • No TEAEs leading to withdrawal • No dose limiting toxicities or drug related liver injury were observed • Effects on hepcidin, serum iron, transferri
Slide 33: Promising Data of siRNA Driven TMPRSS6 Silencing in Mouse Model of Polycythemia Vera
Promising Data of siRNA Driven TMPRSS6 Silencing in Mouse Model of Polycythemia Vera Reduced Raised 1 TMPRSS6 2 endogenous 3 Lowered hemoglobin 4 Reduced hematocrit in the liver hepcidin 2.0 2500 25 80 Serum Hepcidin [ng/ml] TMPRSS6/Hprt mRNA **** Hemoglobin [g/dL] 2000 20 Hematocrit [%] 1.5 60 ****
Slide 34: SLN124 Phase 1/2 Study in Polycythemia Vera (PV)
SLN124 Phase 1/2 Study in Polycythemia Vera (PV) Phase 1 is an open-label, dose-finding study Design Phase 2 is a randomized, double-blind, placebo-controlled study Aim Assess the safety, tolerability, efficacy, PK, and PD response of SLN124 s.c. dosing in patients with PV Enrollment ~ 65 participan
Slide 35: Maximizing Output through the Silence Platform
Maximizing Output through the Silence Platform High-quality target identification using translational genomics Lower attrition rates in discovery enabled by machine learning GalNAc strategic partnerships to enhance pipeline opportunities 35
Slide 36: Financial Highlights
Financial Highlights SLN: Nasdaq Stock Price (9/30/22) $ 10.04 per ADS Common Shares Outstanding (8/30/22) 107,665,212 / ~35,888,404 ADS Market Capitalization (9/30/22) ~$350m Proforma Cash (8/16/22) ~$100m* Debt $0 *Proforma cash balance includes ~$62.8m / £51.6m at the end of June 2022 plus ~$53m
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