Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (March 2026)
41 slides from Silence Therapeutics's investor presentation, Mar 5, 2026
Slide 1: March 2026 Corporate Presentation
March 2026 Corporate Presentation 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: Silencing diseases through precision engineered siRNA medicines
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Slide 4: 2025 Key Milestones Achieved
2025 Key Milestones Achieved Achieved rapid enrollment in SANRECO Phase 2 PV study - topline results anticipated in 3Q 2026 Completed core Phase 3 readiness activities for zerlasiran in high Lp(a) Generated promising pre-clinical results for two new GOLD platform programs Advanced extra-hepatic cell
Slide 5: Our Global Footprint
Our Global Footprint US OFFICE R&D OPERATIONS COMPANY HQ NEW JERSEY LONDON BERLIN siRNA expertise spanning drug discovery, design and clinical development
Slide 6: We are Silencing Genes to Treat Disease
We are Silencing Genes to Treat Disease Natural: RNAi is a natural biological process that regulates gene expression Precise: each siRNA is intentionally designed to bind only to the target gene transcript Durable, yet Reversible: siRNA therapies can be administered infrequently and do not produce p
Slide 7: Our Toolbox Considers all Elements of siRNA and Ligand Design
Our Toolbox Considers all Elements of siRNA and Ligand Design siRNA matched to target gene Silence has developed chemical modification patterns that enhance stability and improve activity Silence has developed proprietary linkers, enabling the attachment of targeting ligands to the siRNA molecule Ga
Slide 8: Development Pipeline of siRNA Therapies
Development Pipeline of siRNA Therapies Preclinical Phase I Phase II Phase III Divesiran (TMPRSS6) SLN548 (CFB) Zerlasiran (LPA) SLN312* (ANGPTL3) SLN365 (GPR146) SLN098 (INHBE) Other Blood Disorders Complement Polycythemia Vera HoFH Obesity RARE CARDIOMETABOLIC Dyslipidemia Cardiovascular Disease *
Slide 9: Divesiran (TMPRSS6)
Divesiran (TMPRSS6)
Slide 10: Divesiran: Potential First-in-Class, First-Line siRNA Treatment for PV
Divesiran: Potential First-in-Class, First-Line siRNA Treatment for Polycythemia Vera (PV) Robust, rapid and durable efficacy in Ph1 Favorable and potentially differentiated safety profile Broad potential in iron-related disorders Less frequent dosing (every 6 or 12 weeks) Fixed dosing, no titration
Slide 11: Polycythemia Vera is a Rare Blood Cancer with Significant Unmet Needs
Myeloproliferative neoplasm characterized by the excessive production of red blood cells (RBCs) Elevated hematocrit (HCT) is a hallmark of the disease, indicating overproduction of RBCs Associated with JAK2 gain-of-function driver mutation in hematopoietic stem cells in over 90% of patients Serious,
Slide 12: People Living with PV Have Significant Unmet Needs
People Living with PV Have Significant Unmet Needs Inconsistent HCT Control Patients with HCT between 45-50% are ~4x more likely to die from CV causes or have major thrombotic events than those <45%1 Most patients have uncontrolled HCT with tests ≥45%2 Iron Deficiency Most patients with PV are iron
Slide 13: SANRECO Phase 1 Study Overview
SANRECO Phase 1 Study Overview Completed in February 2025 Design 34-week, open-label, dose-finding study of divesiran in 21 phlebotomy-dependent PV patients Study included 16-week follow-up period following last administered dose Key Inclusion Criteria PV diagnosis At least 3 phlebotomies in the las
Slide 14: Divesiran Reduced Phlebotomy Frequency in All PV Patients
Divesiran Reduced Phlebotomy Frequency in All PV Patients Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; Pre-dose from D-201 to D-
Slide 15: Divesiran Reduced Hematocrit in All PV Patients
Divesiran Reduced Hematocrit in All PV Patients Regardless of Baseline Levels Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; 2. Or
Slide 16: Divesiran Reduced Hemoglobin in All Cohorts
Divesiran Reduced Hemoglobin in All Cohorts 1. Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; 2. Orange dotted line represent dosi
Slide 17: Divesiran Treatment Produced Sustained Increases in Hepcidin
Divesiran Treatment Produced Sustained Increases in Hepcidin 1. Data Presented at the European Hematology Association. June 12, 2025. SANRECO, an On-going Phase 1/2 Study Evaluating Divesiran, Novel GalNAc-conjugated SiRNA, in Patients with Polycythemia Vera. Abstract Code: SS24; 2. Orange dotted li
Slide 18: Divesiran Demonstrated a Favorable Safety and Tolerability Profile
Divesiran Demonstrated a Favorable Safety and Tolerability Profile Divesiran was well tolerated with no dose-limiting toxicities No treatment-related serious adverse events or TEAEs leading to discontinuation
Slide 19: SANRECO Phase 1 Results Highlight Potential for First-in-Class siRNA Treatment for PV
SANRECO Phase 1 Results Highlight Potential for First-in-Class siRNA Treatment for PV EFFICACY SAFETY DURABILITY Controlled HCT levels and eliminated the need for phlebotomy in target population Effects sustained during the treatment and follow-up period with Q6W dosing Well tolerated with no dose-l
Slide 20: SANRECO Phase 2 Study Overview
SANRECO Phase 2 Study Overview Design 36-week, placebo-controlled, double-blind period followed by a 3-year, double-blind and open-label extension period evaluating divesiran in 48 phlebotomy-dependent PV patients Key Inclusion Criteria PV diagnosis At least 3 phlebotomies in the last 6 months or 5
Slide 21: Zerlasiran (LPA)
Zerlasiran (LPA)
Slide 22: Zerlasiran Silences Lp(a): an Independent Risk Factor for Cardiovascular Disease
Zerlasiran Silences Lp(a): an Independent Risk Factor for Cardiovascular Disease Zerlasiran Has the Potential to Address Major Unmet Needs in Cardiovascular Disease Lp(a) levels are genetically determined Recognized as a major untreated risk factor in cardiovascular disease Lp(a) levels are not sign
Slide 23: Zerlasiran Has Substantial Market Potential
Zerlasiran Has Substantial Market Potential 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 Total Cholesterol1 US ≥ 200 mg/dL EU5 ≥ 190 mg/dL Lipitor® (atorvastatin)
Slide 24: Zerlasiran Phase 2 Results Support Competitive Profile
Zerlasiran Phase 2 Results Support Competitive Profile with Opportunities to Further Differentiate in Phase 3 EFFICACY SAFETY DURABILITY Maximum Lp(a) reductions over 90% Lp(a) reductions persisted 60 weeks following first dose (Q16W and Q24W dosing) Well tolerated with no major safety issues 1. Jou
Slide 25: Zerlasiran Program Status
Zerlasiran Program Status Core Phase 3 readiness activities complete Alignment with global regulatory agencies on Phase 3 design and endpoints Next Steps: Seeking potential third-party partners for Phase 3 development First industry CVOT evaluating Lp(a) lowering therapy impact on cardiovascular eve
Slide 26: SLN312 (ANGPTL3)
SLN312 (ANGPTL3)
Slide 27: SLN312: Phase 1 siRNA with a Competitive Profile for Dyslipidemia
SLN312: Phase 1 siRNA with a Competitive Profile for Dyslipidemia SLN312 is a Phase 1 siRNA silencing ANGPTL3 ANGPTL3 inhibitors are novel class of therapeutic agents with LDL receptor-independent mechanism of action that may benefit patients that do not respond to statins or PCSK9 inhibitors Discov
Slide 28: SLN312 Phase 1 Results Demonstrate Robust ANGPTL3 Reductions
SLN312 Phase 1 Results Demonstrate Robust ANGPTL3 Reductions Supporting Potential for Infrequent Dosing EFFICACY SAFETY DURABILITY Substantial and dose-dependent reductions in ANGPTL3, triglycerides and atherogenic lipoproteins Sustained effects after single and multiple doses supporting potential f
Slide 29: SLN365 (GPR146)
SLN365 (GPR146)
Slide 30: SLN365: Potential First-in-Class siRNA with Novel MOA
SLN365: Potential First-in-Class siRNA with Novel MOA in High Unmet Need Space Potential First-in-Class siRNA Silencing GPR146 Novel mechanism-of-action for managing cholesterol levels independent of LDL-C receptor (LDLR) function Hypercholesterolemia is a highly prevalent indication: around 1 in 30
Slide 31: GPR146: Novel Target for Cholesterol Management Independent of LDLR
GPR146: Novel Target for the Management of Cholesterol Independent of LDL-C Receptor Function LPL=Lipoprotein Lipase Note: Cholesterol modulating mechanism in other tissues not represented VLDL hepatocyte blood GPR146 ligand SREBP2 pathway VLDL secretion LDL ANGPTL3 PCSK9 LDLR Cholesterol degradatio
Slide 32: Genetic Evidence: GPR146 Deficiency Protects Against Hypercholesterolemia
Genetic Evidence: GPR146 Deficiency Protects Against Hypercholesterolemia and Atherosclerosis Common rs2362529-C allele lower GPR146 expression lower LDL-C, ApoB, HDL, apoAI, and CRP Common rs1997243-G allele higher GPR146 expression exact opposite phenotype Human Genetic Studies Support GPR
Slide 33: Dose-Dependent GPR146 mRNA Knockdown with SLN365 in Non-Human Primates
Results SLN365 treatment resulted in 84% mRNA KD at 4 weeks in the multiple dose group (3 x 3 mg/kg) Sustained KD throughout the study duration – 70% mRNA KD at week 12 in the multiple dose group Single dose of 9 mg/kg resulted in 80% mRNA KD at 4 weeks and 63% KD at week 12 No major treatment-relat
Slide 34: Reduction of Plasma Cholesterol and Triglycerides in Mice Following GPR146 siRNA
LDLR KO Reduction of Plasma Cholesterol and Triglycerides in Mice Following GPR146 siRNA Treatment WT Mouse surrogate siRNA reduced Gpr146 mRNA levels by >75% Significant reduction of total cholesterol and triglycerides following siRNA treatment observed in WT and LDLR KO mice on Western diet No acc
Slide 35: SLN098 (INHBE)
SLNO098 (INHBE)
Slide 36: Limitations of Current Obesity Standard of Care Leave Millions at Risk
Despite Recent Advances in Obesity Treatment, Limitations of Current SoC Leave Millions at Risk of Further Complications Need for Improved Quality of Weight Loss with Differentiated Approach to Current Treatments Current obesity treatments offer weight loss of ~15-25% which plateaus after 12-24 mont
Slide 37: SLN098 Silences INHBE: Novel Target for Obesity
SLN098 Silences INHBE: Novel Target for Obesity Supported by Human Genetics and Recent Clinical Validation Potential to Transform Weight Loss Opportunity to address unmet needs including increasing fat loss, preventing muscle mass loss and slowing weight regain INHBE is a novel target supported by h
Slide 38: Targeting INHBE Synthesis Blocks Signalling via ALK7
Targeting INHBE Synthesis Blocks Signalling via ALK7, Effectively Enabling Lipolysis in Adipose Tissue INHBE (Inhibin beta E) encodes Activin beta E, a peptide hormone & member of the Transforming Growth Factor Beta (TGF-b) super family Expression is elevated upon fasting, in obesity and in patients
Slide 39: SLN098 Preclinical Data Anticipated in 2Q 2026
SLN098 Preclinical Data Demonstrating Impact on Weight Loss in Obesity Disease Model Anticipated in 2Q 2026 Study Objectives: SLN098 impact on weight gain SLN098 impact on weight loss in combination with GLP/GIP agonist SLN098 impact on quality of weight loss (lean mass/fat mass & impact on weight g
Slide 40: Anticipated 2026 Milestones
Anticipated 2026 Milestones 1Q 2026 2Q 2026 3Q 2026 4Q 2026 SANRECO Ph2 topline results Divesiran Polycythemia Vera SLN098 Obesity Extra-hepatic Preclinical data Results from first industry CVOT in high Lp(a) anticipated in 2026 Preclinical data SLN365 HoFH Zerlasiran High Lp(a) IND enabling studies
Slide 41: Silencing diseases through precision engineered medicines
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
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