Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (September 2024)
35 slides from Silence Therapeutics's investor presentation, Sep 5, 2024
Slide 1: Corporate Presentation
Corporate Presentation September 5, 2024
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: Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Slide 4: Silence At a Glance
Silence At a Glance • Zerlasiran (Cardiovascular Disease) – phase 2 program targeting elevated Lp(a) - a genetic Advancing risk factor for CVD impacting up to 20% of the world’s population Clinical Programs • Divesiran (Hematological Disorders) – phase 1/2 program in polycythemia vera – a rare blood
Slide 5: Evolution of Silence
Evolution of Silence siRNA work begins in AIM listing, company named • Focus shifted to GalNAc siRNA our Berlin research labs Silence Therapeutics plc • Robust IP protection • Nasdaq listing siRNA technology 1998 2002 2005-2007 2009-2015 2016-2021 PRESENT Progression of our First core patent LNP-siR
Slide 6: Our Global Footprint
Our Global Footprint LONDON BERLIN COMPANY HQ R&D OPERATIONS NEW JERSEY US OFFICE ~120 EMPLOYEES WORLDWIDE 6
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: Our Strategy to Maximize Our mRNAi GOLD Platform
Our Strategy to Maximize Our mRNAi GOLD Platform Wholly owned programs that focus and leverage the company’s expertise in specific areas with the most opportunity PIPELINE Partnered programs provide collaboration for a broader reach and potential source for non- dilutive capital Strategy balances ri
Slide 9: Proprietary Pipeline
Proprietary Pipeline Indication Target Discovery Preclinical Phase I Phase II Phase III Zerlasiran Cardiovascular LPA (SLN360) Disease Divesiran Polycythemia Vera TMPRSS6 (SLN124) (PV) SLN-COMP-1 Undisclosed Complement- mediated Diseases SLN-COMP-2 Undisclosed SLN-HAN-1* Undisclosed SLN-HAN-2* Undis
Slide 10: Partnership Programs Further Expand Pipeline and Provide Over $5 Billion in Potential Milestones
Partnership Programs Further Expand Pipeline and Provide Over $5 Billion in Potential Milestones Collaboration to discover, develop and commercialize siRNA therapeutics for cardiovascular, renal, metabolic and respiratory diseases • Upfront cash payment of $60 million and an equity investment of $20
Slide 11: 2024 Key Strategic Priorities
2024 Key Strategic Priorities 1 Accelerate Lead Proprietary Clinical Programs 2 Advance Partnered Programs 3 Advance and Expand Proprietary Pipeline 11
Slide 12: Clinical Programs
Clinical Programs 12
Slide 13: Zerlasiran
Zerlasiran Cardiovascular Disease 13
Slide 14: Zerlasiran Targets Lp(a): an Independent Risk Factor for Cardiovascular Disease
Zerlasiran Targets Lp(a): an Independent Risk Factor for Cardiovascular Disease An estimated 20-25% of the global population has Lp(a) levels ≥ 125 nmol/L (~50 mg/dL)1 Lp(a) levels are genetically determined Recognized as a major untreated risk factor in cardiovascular disease Lp(a) levels are not s
Slide 15: Zerlasiran Has Substantial Market Potential
Zerlasiran 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 Treate
Slide 16: CV Event Risk Significantly Increases with High Lp(a) Levels
CV Event Risk Significantly Increases with High Lp(a) Levels Substantial Risk of CV Event at Lp(a) ~90 mg/dL 780 Million Worldwide with >90 mg/dL Lp(a) Event Increased Risk Lp(a) level: >50 mg/dL >90 mg/dL Heart Attack1 2 - 3x Prevalence6 ~20% ~10% Aortic Stenosis2 2 - 3x USA 66m 33m EU 103m 51m Hea
Slide 17: Several 2024 Analyses Show an Inflection in CV Risk Beginning at Low Lp(a) Levels
Several 2024 Analyses Show an Inflection in CV Risk Beginning at Lp(a) Levels as Low as 75nmol/L (30 mg/dL) Wong et al 2024 Beman et al 2024 Lp(a) at levels well below currently accepted risk thresholds correlate with increased CV risk Suggests a wider patient pool could benefit from future prev
Slide 18: Lp(a) is an Inherited Cause of Early Cardiovascular Disease
Lp(a) is an Inherited Cause of Early Cardiovascular Disease Patient Testimonials “I’d been on statins from when I was 20, I had a reasonably healthy lifestyle, I shouldn’t be“I’d been having onstents three statins andfrom when a heart I was bypass 20,I’m before I had 50” a reasonably healthy lifesty
Slide 19: Growing Awareness of Lp(a) as a Key CV Risk Factor
Growing Awareness of Lp(a) as a Key CV Risk Factor FDA Grants Breakthrough Device Designation to Blood Test Measuring Lp(a) 19
Slide 20: Major CV Societies Recommending Lp(a) Testing
Major CV Societies Recommending Lp(a) Testing 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 Lp(a) measurement for history of premature ASCVD at least onc
Slide 21: Zerlasiran Phase 1 Program Overview
Zerlasiran Phase 1 Program Overview • Evaluated participants with elevated Lp(a) greater than 150 nmol/L • Healthy volunteers showed Lp(a) reductions up to 98% following a single dose with effects persisting over a five-month period • ASCVD patients showed Lp(a) reductions up to 99% following repeat
Slide 22: Zerlasiran Produced Significant and Sustained Lp(a) Reductions in Phase 1 Multiple Dose Study
Zerlasiran Produced Significant and Sustained Lp(a) Reductions in Phase 1 Multiple Dose Study 1. Journal of the American Medical Association (JAMA). April 8, 2024. Single Ascending and Multiple-Dose Trial of Zerlasiran, a Short Interfering RNA Targeting Lipoprotein(a): A Randomized Clinical Trial |
Slide 23: Zerlasiran Phase 2 Study Overview
Zerlasiran Phase 2 Study Overview • Evaluating ASCVD patients with elevated Lp(a) greater than 125 nmol/L over 60 weeks • Study met primary endpoint and demonstrated a highly significant reduction from baseline in Lp(a) compared to placebo to week 36 • Median maximum Lp(a) reduction of approximately
Slide 24: Divesiran
Divesiran Hematological Disorders 24
Slide 25: Polycythemia Vera (PV): A Rare Blood Cancer We Are Targeting
25 Polycythemia Vera (PV): A Rare Blood Cancer We Are Targeting • Myeloproliferative neoplasm characterized by the excessive production of red blood cells (RBCs) Treatment goal is o Elevated hematocrit (HCT) is a hallmark of the disease, indicating overproduction of RBCs to control HCT <45% to reduc
Slide 26: People Living with PV Experience Significant Unmet Needs
26 People Living with PV Experience Significant Unmet Needs Inconsistent HCT Iron Deficiency Disease Burden Control • Patients with HCT between • Most patients with PV are • Patients with elevated HCT 45-50% are ~4x more likely iron deficient due to depleted often require frequent to die from CV cau
Slide 27: Divesiran Has the Potential to Be First siRNA for PV
27 Divesiran Has the Potential to Be First siRNA for PV Divesiran targets Proof of mechanism Positive results from TMPRSS6 and modulates demonstrated in ongoing SANRECO hepcidin – the body’s healthy volunteer Phase 1 study in PV master iron regulator study patients Divesiran has FDA Fast Track and O
Slide 28: Divesiran Rationale for Targeting TMPRSS6
28 Divesiran Rationale for Targeting TMPRSS6 HJV BMPR Macrophages > TMPRSS6 is a negative regulator of the BMP BMP/SMAD signaling pathway; activation of the pathway induces hepcidin expression Ferroportin > Hepcidin reduces uptake of dietary iron and the P release of iron from storage cells TMPRSS6
Slide 29: SANRECO Phase 1 Study of Divesiran in PV Patients
SANRECO Phase 1 Study of Divesiran in PV Patients Design Open-label, dose-finding study • PV diagnosis Key • At least 3 phlebotomies in the last 6 months or 5 in the last year prior to screening Inclusion • Stable dose of cytoreductive agents allowed Criteria • Patients with baseline HCT levels ≤ 45
Slide 30: SANRECO Interim Results Showed Divesiran Substantially Reduced Phlebotomy Requirements
SANRECO Interim Results Showed Divesiran Substantially Reduced Phlebotomy Requirements in PV Patients Phlebotomy History Note: 1006-1002: phlebotomy Day 1 pre-dose 6 mos prior Screening EoS 239 1. Silence Therapeutics. June 27, 2024. Silence Therapeutics Announces Positive Results from Ongoing SANRE
Slide 31: Divesiran Elevated Hepcidin in PV Patients, Demonstrating Robust Target Engagement
Divesiran Elevated Hepcidin in PV Patients, Demonstrating Robust Target Engagement 16 Cohort 1 (n = 4) 14 12 Cohort 2 (n = 8) Hepcidin (nM) 10 Dosing 8 6 4 2 0 -2 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: Error bars represent +/- 1 SD 1. Silence Therapeutics. June 27, 2024. Silence Thera
Slide 32: Divesiran Treated PV Patients Achieved Target HCT Levels of 45% or Below
Divesiran Treated PV Patients Achieved Target HCT Levels of 45% or Below 55 Cohort 1 (n = 4) Cohort 2 (n = 8) Haematocrit (%) 50 Dosing 45 40 35 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Days Note: Error bars represent +/- 1 SD 1. Silence Therapeutics. June 27, 2024. Silence Therapeutics Announce
Slide 33: Divesiran Has Been Well Tolerated To-Date
Divesiran Has Been Well Tolerated To-Date • No drug related SAEs • No withdrawals due to divesiran related AEs • Mild injection site reactions (ISRs) have been reported, all grade one and fully resolved Positive Phase 1 Interim Results Support Advancing to Phase 2 By Year-End 1. Silence Therapeutics
Slide 34: Key Investment Highlights
Key Investment Highlights Advancing multiple wholly owned clinical programs • Zerlasiran targeting large CV market with multi billion-dollar potential • Divesiran poised to be the first siRNA for PV Progressing existing partnerships and new opportunities • AstraZeneca collaboration now in the clinic
Slide 35: Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Silencing Silencingdiseases diseasesthrough through precision precisionengineered engineeredmedicines medicines created createdwith withproprietary proprietary siRNA siRNAtechnology technology 35
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