Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (November 2022)
34 slides from Silence Therapeutics's investor presentation, Nov 16, 2022
Slide 1: Silence Therapeutics
Silence Therapeutics November 16, 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: Geographic Operations
Geographic Operations COMPANY HQ R&D OPERATIONS US OFFICE 124 employees worldwide 4
Slide 5: 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 6: 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 7: 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 8: 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 8
Slide 9: 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 10: 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 11: 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 12: Clinical Programs
Clinical Programs 12
Slide 13: 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 Lp(a) reductions Effects persisting Well tolerated with no LPA volunteers SLN360 observed up to 98% over a five-month clinically
Slide 14: SLN360
SLN360 Cardiovascular Disease 14
Slide 15: 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 16: 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 17: 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 Lifestyle changes can have a positive impact High Lp(a) is a Genetic Risk Factor Lifestyle changes have no effect on Lp(a) levels Similar Medically Treated Po
Slide 18: Growing Awareness of Lp(a) as a Key CV Risk Factor
Growing Awareness of Lp(a) as a Key CV Risk Factor 2022 European 2021 Canadian 2018 AHA/ACC Atherosclerosis Society Cardiovascular Society Consensus Statement (CCS) Relative indications for its measurement are a family Lp (a) should be measured CCS recommends Lp (a) history of premature ASCVD at lea
Slide 19: 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 20: 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 21: Results Presented at ACC and Published in JAMA in April 2022
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 22: 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 23: SLN124
SLN124 Hematological Disorders 23
Slide 24: SLN124 Has Potential for Broad Mechanistic Mode of Action Approach
24 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 25: SLN124 Clinical Programs
SLN124 Clinical Programs Iron Loading Anemias (Beta Thalassemia) • Globin gene mutations interfere with red blood cell production and cause anemia ~5,000 • The majority are dependent on regular blood transfusions (TDT), Prevalence while others are transfused less frequently (NTDT) 1/100,0001,2,3 ~10
Slide 26: 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 27: 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 28: 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 29: 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 30: 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, no 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, transfe
Slide 31: 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 32: 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 32
Slide 33: Financial Highlights
Financial Highlights SLN: Nasdaq Stock Price (11/14/22) $ 13.89 per ADS Common Shares Outstanding (9/30/22) ~35,893,337 ADS Market Capitalization (11/14/22) ~$500m Cash (9/30/22) ~$113m Debt $0 Note: ADS each represent 3 ordinary shares nominal value 33
Slide 34: Key Potential Value Drivers
Key Potential Value Drivers Wholly owned SLN360 program targeting large cardiovascular indication with high unmet need – on-track to start phase 2 study by year end Second wholly owned SLN124 program has shown potential in multiple rare hematological diseases – on-track to start phase 1/2 PV stu
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