Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — 30th European Hematology Association (EHA) Congress 2025
17 slides from Alnylam Pharmaceuticals's conference presentation, Jun 12, 2025
Slide 1: Hepatic plasminogen lowering with RNAi unlikely to pose thrombotic risk
Hepatic plasminogen lowering with RNA interference for the treatment of bleeding disorders is unlikely to pose thrombotic risk based on UK Biobank analyses and mouse models of provoked thrombosis Lacramioara Ivanciu1,2, Lynne Krohn3, Caitlin Cevasco3, Aimee M Deaton3, Lucas D Ward3, Philip J LoGerfo
Slide 2: Disclosures
Disclosures Presenter: Rodney Camire, PhD Conflict Disclosure Alnylam Pharmaceuticals Research Funding ALN-6400: ALN-6400 is an investigational drug being studied for the treatment of bleeding disorders. ALN-6400 is not approved by any health authority, and the safety and efficacy of ALN-6400 have n
Slide 3: Large Unmet Need in the Treatment of Bleeding Disorders
Large Unmet Need in the Treatment of Bleeding Disorders A substantial number of patients are affected by bleeding disorders, with global recognition and prevalence on the rise1 Bleeding disorders have a major impact on quality of life and lead to life- threatening complications for patients2-5 Curre
Slide 4: Plasminogen is a Key Player in Fibrinolysis and Hemostasis
Plasminogen is a Key Player in Fibrinolysis and Hemostasis Therapeutic Hypothesis • Plasminogen (PLG) is produced primarily in the liver1 • Lowering hepatic PLG with RNA interference has potential to be a longer lasting, more effective, and safer approach than current antifibrinolytics, and may act
Slide 5: UK Biobank Analyses
| || UK Biobank Analyses
Slide 6: Methodology for Computational Analyses in the UK Biobank
Methodology for Computational Analyses in the UK Biobank Using human genetics and proteomics data via the UK Biobank, we assessed whether low plasma PLG protein levels were associated with increased risk for thrombosis • Linear regression used to test whether lower PLG levels were correlated with th
Slide 7: Low Levels of PLG are Not Associated with Thrombosis
Low Levels of PLG are Not Associated with Thrombosis PLG plasma protein levels are not MR results support no causal effect of correlated with thrombosis lower PLG on thrombotic risk (p>0.05) 0-12.5% mean levels N=68 No increased thrombotic risk Antithrombin • Thrombosis incidence is not higher among
Slide 8: RNAi Harnesses an Endogenous Process to Lower Target Protein Production
RNAi Harnesses an Endogenous Process to Lower Target Protein Production GalNAc- conjugated liver directed siRNA 3. RISC–target Synthetic double-stranded small complex formed by interfering RNA (siRNA) is designed 2. siRNA enters complementary to target specific mRNA1–3 RISC and unzips pairing betwee
Slide 9: Mouse Injury Model Analyses
| [| Mouse Injury Model Analyses
Slide 10: Evaluation of Thrombus Formation with Hepatic PLG Lowering
Evaluation of Thrombus Formation with Hepatic PLG Lowering Methodology Using the Cremaster Arteriole Laser‐Induced Injury Mouse Model 1. Wild-type mice received a single subcutaneous injection of one of: Argon-Krypton Laser • PLG siRNA • Antithrombin (AT3) siRNA (positive control) WIDEFIELD CCD CONF
Slide 11: No Increase in Thrombus Formation with ~99% PLG Lowering
No Increase in Thrombus Formation with ~99% PLG Lowering Comparable Platelet/Fibrin Accumulation between PLG siRNA and Vehicle Treated Mice Platelets Fibrin AT3 siRNA (~96% KD of AT3) PLG siRNA (~99% KD of PLG) Vehicle (PBS) Platelets/Fibrin AT3 siRNA PLG siRNA PBS treated AT3, antithrombin; KD, kno
Slide 12: Evaluation of Vessel Occlusion with Hepatic PLG Lowering
Evaluation of Vessel Occlusion with Hepatic PLG Lowering Methodology Using the FeCl3-Induced Carotid Arterial Thrombosis Mouse Model 1. Wild-type mice received a single subcutaneous injection of one of: • PLG siRNA • Negative control (non-targeting) siRNA 2. 14 days post-dose: a) Carotid artery in a
Slide 13: No Difference in Speed of Thrombus Formation with ~99% PLG Lowering
No Difference in Speed of Thrombus Formation with ~99% PLG Lowering Comparable Time to Vessel Occlusion between PLG siRNA and Control siRNA Treated Mice Non-Significant Difference in Time to Occlusion Between Groups Control PLG siRNA siRNA ~13 min to ~13.4 min vessel to vessel occlusion occlusion Re
Slide 14: Results Support Clinical Development of ALN-6400
Results Support Clinical Development of ALN-6400, an Investigational RNAi Therapeutic for Bleeding Disorders A Phase 1, Double-Blind, Placebo-Controlled, Single Ascending Dose Study of ALN-6400 is Ongoing in Healthy Adult Volunteers ALN-6400 Dose 1 or placebo ALN-6400:placebo 3:1 randomization Run-i
Slide 15: Summary
Summary • In this analysis of UK Biobank data, low levels of plasma PLG protein were not associated with thrombotic risk • Additionally, in two different mouse injury models, thrombus formation was similar in controls compared to those with ~99% lowering of hepatic PLG using a liver-directed siRNA •
Slide 16: Back Up
| || Back Up
Slide 17: No Increase in Thrombus Formation with ~99% PLG Lowering
No Increase in Thrombus Formation with ~99% PLG Lowering Comparable Platelet/Fibrin Accumulation between PLG siRNA and Vehicle Treated Mice Platelets Fibrin AT3 siRNA (~96% KD of AT3) PLG siRNA (~99% KD of PLG) Vehicle (PBS) Platelets/Fibrin AT3 siRNA PLG siRNA PBS treated AT3, antithrombin; KD, kno
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