Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (July 2024)
33 slides from Silence Therapeutics's investor presentation, July 2024
Slide 1: Corporate Presentation July 2024
Corporate Presentation July 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
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: Elevated Lipoprotein(a): a Major Untreated Risk Factor in Cardiovascular Disease
Elevated Lipoprotein(a): a Major Untreated Risk Factor in 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 reaso
Slide 15: 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 16: 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 17: 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 18: Cardiovascular History Impacts Lp(a) Risk
Cardiovascular History Impacts Lp(a) Risk • Recent US based registry study in over 16,000 individuals showed there is substantial risk of major adverse CV events in individuals with elevated Lp(a) levels below the currently accepted risk threshold of 125 nmol/L (~50 mg/dL) Berman, Adam N., et al. "L
Slide 19: 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 Lp(a) measurement for history of premature ASCVD at leas
Slide 20: 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 21: 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 22: 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 23: Divesiran
Divesiran Hematological Disorders 23
Slide 24: Polycythemia Vera (PV): A Rare Blood Cancer We Are Targeting
24 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 25: People Living with PV Experience Significant Unmet Needs
25 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 26: Divesiran Has the Potential to Be First siRNA for PV
26 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 27: Divesiran Rationale for Targeting TMPRSS6
27 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 28: 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 29: SANRECO Interim Results Showed Divesiran Substantially Reduced Phlebotomy Requirements
SANRECO Interim Results Showed Divesiran Substantially Reduced Phlebotomy Requirements in PV Patients Based on a data cutoff date of March 29, 2024 (16 patients) Phlebotomy History 6 mos prior Screening EoS 239 1. Silence Therapeutics. June 27, 2024. Silence Therapeutics Announces Positive Results f
Slide 30: SANRECO Interim Results Showed Divesiran Treated PV Patients Achieved Target HCT Levels
SANRECO Interim Results Showed Divesiran Treated PV Patients Achieved Target HCT Levels of 45% or Below Based on a data cutoff date of March 29, 2024 (16 patients) 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 ba
Slide 31: Data Highlights from Ongoing SANRECO Study
Data Highlights from Ongoing SANRECO Study Based on a data cutoff date of 29 March 2024 (16 patients) Efficacy • All divesiran treated patients who were well controlled at baseline remained so without the need for phlebotomy • All patient groups, regardless of baseline HCT, demonstrated reduction an
Slide 32: 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 33: Silencing diseases through precision engineered medicines
Silencing Silencingdiseases diseasesthrough through precision precisionengineered engineeredmedicines medicines created createdwith withproprietary proprietary siRNA siRNAtechnology technology 33
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