Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (May 2021)
32 slides from Silence Therapeutics's investor presentation, May 19, 2021
Slide 1: May 2021 Corporate Presentation
May 2021 Corporate Presentation Silence Therapeutics Exhibit 99.2
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: Poised for Transformation in 2021
Poised for Transformation in 2021 Two decades of know-how combined with robust and growing IP estate Global footprint – R&D in Berlin, headquarters in London and NYC office Pioneers in RNAi Clinical data demonstrated safety, robust gene knockdown and long duration of action Anticipate 2-3 INDs per y
Slide 4: We believe the Path to Value Creation is Clear
Market Capitalization as of May 18, 2021 Pipeline programs = company disclosed partnered and wholly owned programs discovery phase – marketed We believe the Path to Value Creation is Clear $Billion Highest phase: Commercial 31+ pipeline programs, 4 in registration/commercial, 7 in the clinic, 9+ who
Slide 5: Executive Leadership Team with Deep Sector Experience
Executive Leadership Team with Deep Sector Experience Mark Rothera President and CEO 30+ years of experience in the biopharmaceutical industry Former President & CEO of Orchard Therapeutics and CCO of PTC Therapeutics Drove the transition of multiple emerging biotech companies from R&D stage to comm
Slide 6: siRNA Can Inhibit Expression of Disease-Associated Genes
siRNA Can Inhibit Expression of Disease-Associated Genes HEALTHY DISEASE nucleus cytoplasm DNA Genes encode messages for all features in the body In certain diseases the DNA is mutated or abnormally expressed mRNA is then made into proteins. Proteins are responsible for most functions in the body Th
Slide 7: siRNA Can Precisely Target and Silence Disease-Associated Genes
siRNA Can Precisely Target and Silence Disease-Associated Genes Mutated DNA mRNA is degraded and gene is “silenced” Reduction in disease- causing protein Target-specific short interfering RNA (siRNA) binds to the mRNA mRNA Natural Harnesses natural cellular mechanisms present in every cell in the hu
Slide 8: Our Toolbox Considers all Elements of siRNA and Ligand Design
Our Toolbox Considers all Elements of siRNA and Ligand Design siRNA molecule GalNAc Ligand (delivery tool) siRNA matched to target gene Silence has developed chemical modifications patterns that enhance stability and improve activity Silence has developed proprietary linkers, enabling the attachment
Slide 9: Platform Approach: Precision-Engineered Therapies
Platform Approach: Precision-Engineered Therapies High-quality discovery programs Improves molecular design Maximizes efficacy Minimizes off-target effects Stabilizes molecules Ensures ease of manufacturing Robust and growing IP estate GalNAc OLigonucleotide Discovery Platform
Slide 10: We Believe the Opportunity for our Platform is Substantial
We Believe the Opportunity for our Platform is Substantial Only ~1% of genes expressed in the liver have been targeted by publicly known siRNAs Source: Human Protein Atlas, GlobalData Opportunity to identify new siRNAs targeting many of the remaining 99% (~14,000) of liver-expressed genes Existing R
Slide 11: mRNAi GOLD Pipeline Targets
mRNAi Our ¢GOLD Pipeline Targets ProprietaryiPartnered SLN360 Cardiovascular disease with high Lp(a) LPC) I SILENCE LN124 Thalassemia TMPRSS6 JA SILENCE ‘SLN124 Siero ost TMPRSS6 H)SILENCE Multiple programs maa Undisclosed H{SILENCE Complement ‘SLN500 mediated diseases Complement. SESE modiated dise
Slide 12: 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 (e.g. target selection)
Slide 13: Early-stage GalNAc-conjugated RNAi Programs Have Greater Likelihood of Approval
Early-stage GalNAc-conjugated RNAi Programs Have a Much Greater Likelihood of Approval vs. Industry Average Phase success is defined as the movement of the program to the next phase, not an evaluation of whether endpoints were met. GalNAc-conjugated RNAi includes both GalNAc-conjugated siRNA and Gal
Slide 14: SLN360 for Cardiovascular Disease Due to High Lp(a)
SLN360 for Cardiovascular Disease Due to High Lp(a)
Slide 15: Targeting Lp(a) with SLN360 Could Address Major Unmet Needs
Targeting Lp(a) with SLN360 has the potential to address major unmet needs in cardiovascular disease SLN360 Targets Lipoprotein(a) or Lp(a): an Independent Risk Factor for Cardiovascular Disease 1 Varvel et al. Arterioscler Thromb Vasc Biol. 2016;36:2239, Tsimikas et al. Atherosclerosis. 2020;300:1
Slide 16: Cardiovascular Event Risk Significantly Increases with High Lp(a)
Cardiovascular Event Risk Significantly Increases with High Lp(a) Heart Attack1 2 - 3x Aortic Stenosis2 2 - 3x Heart Failure3 1.6 - 1.8x Ischemic Stroke4 1.2 - 1.6x Mortality5 (all cause/CV) 1.2 - 1.7x Increased Risk Event Substantial Risk of CV Event at Lp(a) ~90 mg/dL 780 Million Worldwide with >9
Slide 17: Lp(a)-lowering Drugs Present Similar Opportunity to Cholesterol-lowering Drugs
Lp(a)-lowering Drugs Present a Similar Opportunity to Cholesterol-lowering Drugs, Which Had Sales of >$30B at Peak Blockbuster Potential Similar Medically Treated Population Patients with High Total Cholesterol vs. High Lp(a) US + EU5 Markets High Lp(a)2 ≥ 50 mg/dL (no indicated treatments) High Tot
Slide 18: SLN360 Demonstrated Ideal Profile in NHP Model
SLN360 demonstrated ideal profile in NHP model Efficacy: Robust Lp(a) knockdown observed after first dose (>90%) Durability: Sustained reduction of Lp(a) serum levels (>90%) for duration of study Safety: <1% exposure outside liver with no detected off target effects Serum Lp(a) reduction SLN360 Demo
Slide 19: SLN360 Phase 1 Program Overview
SLN360 Phase 1 Program Overview PD: Pharmacodynamics; PK: Pharmacokinetics Now enrolling – Data from single- ascending dose portion expected in H2 2021
Slide 20: SLN124 for Iron-Loading Anemia Conditions
SLN124 for Iron-Loading Anemia Conditions
Slide 21: SLN124: Addressing a Major Unmet Need in Thalassemia and MDS
SLN124: Addressing a Major Unmet Need in Thalassemia and Myelodysplastic Syndrome (MDS) Group of rare malignant blood disorders that impact older patients Low quality of life and poor response to current therapies Burdens include severe anemia, transfusion dependence, toxic iron overload Progression
Slide 22: SLN124 Aims to Reduce Anemia and the Need for Blood Transfusions
SLN124 Aims to Reduce Anemia and the Need for Blood Transfusions and Iron Chelation Therapies SLN124 is Designed to Restore Endogenous Hepcidin and Normalize Iron Levels Study performed in a rodent model for beta thalassemia (Hbbth3/+); *** p≤0.001
Slide 23: SLN124 Healthy Volunteer Study Design
SLN124 Phase 1 Healthy Volunteer Study Design PD: Pharmacodynamics; PK: Pharmacokinetics
Slide 24: Strong Positive Results from SLN124 Healthy Volunteer Study
Strong Positive Results from SLN124 Healthy Volunteer Study First clinical data from mRNAi GOLD™ platform Demonstrates proof of mechanism for SLN124 All 3 dose levels of SLN124 were safe and generally well-tolerated No serious or severe treatment emergent adverse events (TEAEs) or TEAEs leading to w
Slide 25: SLN124 Increased Average Hepcidin up to ~4-Fold
SLN124 Increased Average Hepcidin up to ~4-Fold After a Single Dose with Effect Sustained for ≥ 2 Months n=6 healthy volunteers in each treatment group
Slide 26: SLN124 Reduced Serum Iron by ~50%
SLN124 Reduced Serum Iron by ~50% After a Single Dose with Effect Sustained for ≥ 2 Months n=6 healthy volunteers in each treatment group
Slide 27: SLN124 Study in Adult Thalassemia and MDS
SLN124 Phase 1 Study in Adult Thalassemia and MDS MDS: myelodysplastic syndrome; PD: Pharmacodynamics; PK: Pharmacokinetics; VL/LR-MDS: very low- and low-risk MDS Now enrolling - Data expected in H2 2021
Slide 28: Major Potential Value Creating Milestones in 2021
Note: all programs are at potential risk of delay due to COVID-19 = data milestone Major Potential Value Creating Milestones in 2021 = positive data reported
Slide 29: Partnership Programs Provide Up to $6 Billion in Potential Milestones
Partnership Programs Further Expand Pipeline and Provide Up to $6 Billion in Potential Milestones Plus Royalties Signed major deal to discover, develop and commercialize siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases in March 2020 Upfront cash payment of $60 million
Slide 30: Developing a New Extra-Hepatic siRNA Delivery Platform
Tap into the huge opportunity to silence genes outside of the liver FUTURE PRESENT Developing a New Extra-Hepatic siRNA Delivery Platform
Slide 31: Financial Highlights
Financial Highlights *includes £37.4m at 12/31/20, plus £30.8m capital raise in Feb’21 and £29.3m due from AstraZeneca in H1’21
Slide 32: Poised for Transformation in 2021
Poised for Transformation in 2021 Two decades of know-how combined with robust and growing IP estate Global footprint – R&D in Berlin, headquarters in London and NYC office Pioneers in RNAi Clinical data demonstrated safety, robust gene knockdown and long duration of action Anticipate 2-3 INDs per y
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