Silence Therapeutics PLC · NASDAQ:SLN
Silence Therapeutics — Investor Presentation (June 2026)
38 slides from Silence Therapeutics's investor presentation, Jun 23, 2026
Slide 1: June 2026 Corporate Presentation
June 2026 Corporate Presentation EXHIBIT 99.1
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: 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 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: 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 7: 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 8: Divesiran (TMPRSS6) Rare Disease
Divesiran (TMPRSS6) Rare Disease
Slide 9: Divesiran: Potential First-in-Class, First-Line siRNA Treatment for Polycythemia Vera
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 10: Polycythemia Vera (PV) 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 11: 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 12: 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 13: 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 14: Divesiran Demonstrated Strong Durability with Several Patients Phlebotomy-Free
Median Time to First Phlebotomy was 287 Days in 14 Patients with Follow-up Data Divesiran Demonstrated Strong Durability with Several Patients Phlebotomy-Free Nearly 1 Year After Last Dose 1. Data Presented at the European Hematology Association. June 11, 2026. Divesiran, a Novel GalNac Conjugated s
Slide 15: 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 line represent dosing dates. Error bars represent ± SEM; All da
Slide 16: Divesiran Reduced Hematocrit and Hemoglobin in All PV Patients
Divesiran Reduced Hematocrit and Hemoglobin 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 Co
Slide 17: 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 18: 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 19: 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 20: SLN312 (ANGPTL3) Cardiometabolic Disease
SLN312 (ANGPTL3) Cardiometabolic Disease
Slide 21: SLN312 Phase 1 Results Demonstrate a Competitive Profile for Dyslipidemia
SLN312 Phase 1 Results Demonstrate 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 inhibitor
Slide 22: 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 23: SLN365 (GPR146) Cardiometabolic Disease
SLN365 (GPR146) Cardiometabolic Disease
Slide 24: SLN365: Potential First-in-Class siRNA with Novel MoA in High Unmet Need Space
SLN365: Potential First-in-Class siRNA with Novel MoA in High Unmet Need Space Novel mechanism-of-action for managing cholesterol levels independent of LDL receptor (LDLR) function Hypercholesterolemia is a highly prevalent indication: around 1 in 300 individuals worldwide have the familial form HeF
Slide 25: GPR146: Novel Target for the Management of Cholesterol Independent of LDL Receptor Function
GPR146: Novel Target for the Management of Cholesterol Independent of LDL 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 degradation
Slide 26: Genetic Evidence: GPR146 Deficiency Protects Against Hypercholesterolemia and Atherosclerosis
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 27: SLN365 Demonstrated Dose-Dependent GPR146 mRNA Knockdown 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 28: Reduction of Plasma Cholesterol and Triglycerides in Mice Following GPR146 siRNA Treatment
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 29: SLN098 (INHBE) Cardiometabolic Disease
SLN098 (INHBE) Cardiometabolic Disease
Slide 30: SLN098 Targets INHBE: Promising Novel Target for Cardiometabolic Disease
SLN098 Targets INHBE: Promising Novel Target for Cardiometabolic Disease Potential to Address Multiple Unmet Needs in Cardiometabolic Disease SLN098 has potential to address unmet needs including reducing total and visceral fat, improving muscle preservation, and slowing weight regain INHBE is a nov
Slide 31: Despite Recent Advances in Obesity Treatment, Limitations of Current SoC 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 32: Targeting INHBE Expression Blocks Signalling via ALK7, Enabling Lipolysis in Adipose Tissue
Targeting INHBE Expression Blocks Signalling via ALK7, Effectively Enabling Lipolysis in Adipose Tissue INHBE (Inhibin beta E) encodes Activin beta E Expression is elevated upon fasting in obesity and in patients with T2D Activin beta E activates ALK7 in adipocytes, where it blocks lipolysis & promo
Slide 33: SLN098 Demonstrated Deep and Durable Knockdown in NHP
SLN098 Demonstrated Deep and Durable Knockdown in NHP: ~90% Protein Knockdown Sustained for at Least 3 Months
Slide 34: SLN098 Significantly Reduces Weight Gain in Mice on High Fat Diet
SLN098 Significantly Reduces Weight Gain in Mice on High Fat Diet Both as Monotherapy and Post Tirzepatide Discontinuation Murine Obesity Mouse Model – Mono Therapy vs Co-treatment with Tirzepatide (TZP) Note: SLN098 was not optimized for use in murine – More robust KD seen in NHP and expected in hu
Slide 35: SLN098 Monotherapy Lowers Visceral Fat and Total Fat Gain While Preventing Lean Mass Loss
SLN098 Monotherapy Lowers Visceral Fat and Total Fat Gain While Preventing Lean Mass Loss in Combination with TZP Read out at week 12 TZP was discontinued at week 8 ~ 65% >45% eWAT Weight [D84] Body Fat [g] ~ 50% >35% Lean Mass [g] ~5%
Slide 36: Potential to Address Major Unmet Needs Through Strategic Combinations
Potential to Address Major Unmet Needs Through Strategic Combinations Improve Quality of Weight Loss Tap into Atherogenic Dyslipidaemia and Associated Metabolic Disorders Skeletal Mass Preservation + Incretins + Lipid Modifiers + Lean Mass Sparing Therapies
Slide 37: 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 38: Silencing diseases through precision engineered medicines created with proprietary siRNA technology
Silencing diseases through precision engineered medicines created with proprietary siRNA technology
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