Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Technical Presentation (October 2018)
15 slides from Alnylam Pharmaceuticals's technical presentation, Oct 25, 2018
Slide 1: Safety and Efficacy Study of Lumasiran in Patients with Primary Hyperoxaluria Type 1
Safety and Efficacy Study of Lumasiran (ALN-GO1), an Investigational RNA Interference (RNAi) Therapeutic, in Patients with Primary Hyperoxaluria Type 1 ASN Annual Meeting | San Diego, CA | 25 October 2018 © 2018 Alnylam Pharmaceuticals, Inc.
Slide 2: Primary Hyperoxaluria Type 1: Rare Genetic Disorder of Increased Oxalate Synthesis
Primary Hyperoxaluria Type 1 Rare Genetic Disorder of Increased Endogenous Oxalate Synthesis Primary Hyperoxaluria Type 1 (PH1): Oxalate Synthesis in PH13: 1. AGT is localized to the liver peroxisome, where it • Due to defect in liver peroxisomal enzyme 1 metabolizes glyoxylate to glycine alanine:gl
Slide 3: Lumasiran: Investigational RNAi Therapeutic for Primary Hyperoxaluria Type 1
Lumasiran Investigational RNAi Therapeutic for Primary Hyperoxaluria Type 1 Lumasiran (ALN-GO1): • SC-administered small interfering RNA (siRNA) Lumasiran Therapeutic Hypothesis: ◦ Harnesses natural RNA interference (RNAi) mechanism ◦ Specifically designed for targeted liver delivery— site of oxalat
Slide 4: Lumasiran Phase 1/2 and Phase 2 OLE Study Design
Lumasiran Phase 1/2 and Phase 2 Open-Label Extension (OLE) Study Design Patients previously dosed in Phase 1/2† study may be eligible to enroll into Phase 2 OLE^ study • All patients who have completed follow up in Phase 1/2 have enrolled to continue dosing in OLE* • Patients who have been dosed in
Slide 5: Phase 1/2 Study Patient Demographics & Exposure: Part B
Lumasiran Phase 1/2 Study* Patient Demographics & Exposure: Part B (Patients with PH1) Baseline Characteristics Result (N=20) Mean age, years (range) 14.9 (6–43) Age <18 years 80% Gender, females 65% Mean weight, kg (range) 49.9 (21.3–110.0) Mean eGFR, mL/min/1.73m2 (range) 77 (42–131) Mean Urine Ox
Slide 6: Phase 1/2 Study Disease Characteristics at Study Entry
Lumasiran Phase 1/2 Study* Disease Characteristics at Study Entry Characteristic Result Time from first symptoms to diagnosis of PH1, mean (years†) (N=13) 1.1 (range: -0.3–5.1) Time from PH1 diagnosis to first dose of lumasiran, mean (years†) (N=20) 11.3 (range: 2.7–30.8) Time from first symptoms of
Slide 7: Phase 1/2 Study Disease Characteristics at Study Entry
Lumasiran Phase 1/2 Study* Disease Characteristics at Study Entry Characteristic Result (N=20) Patients receiving pyridoxine therapy, N (%) 13 (65) Mean baseline urinary oxalate content in patients receiving pyridoxine, mmol/24hr/1.73m2 1.80 (range: 0.83–2.97) Patient history of symptoms at study en
Slide 8: Phase 1/2 Study Initial Results: Safety
Lumasiran Phase 1/2 Study Initial Results* Safety: Part B (Patients with PH1) Multiple doses of lumasiran well tolerated in patients with PH1 • No discontinuations from study treatment • SAEs reported in 1 (33%) patient during placebo dosing and 5 (25%) patients after lumasiran dosing; none related
Slide 9: Phase 2 OLE Study Initial Results: Safety
Lumasiran Phase 2 OLE Study Initial Results* Safety Continued dosing with lumasiran was well tolerated in patients with PH1 • No discontinuations from study treatment • SAEs reported in 2/8 patients (25%); none assessed as related to study drug ◦ 1 patient with traumatic brain injury and contusion†;
Slide 10: Pharmacodynamics: Urinary Oxalate Content in Part B
Lumasiran Phase 1/2 Study Initial Results* Pharmacodynamics: Urinary Oxalate Content in Part B (Patients with PH1) Mean maximal reduction in urinary oxalate of 75% (range: 43-87%) relative to baseline after lumasiran dosing in all cohorts† (n=20) • The mean reduction relative to baseline 28 days pos
Slide 11: Pharmacodynamics: Urinary Oxalate Reduction in Part B
Lumasiran Phase 1/2 Study Initial Results* Pharmacodynamics: Urinary Oxalate Reduction in Part B (Patients with PH1) Urinary Oxalate Reduction Result Mean reduction 28 days post last dose of lumasiran (N=20) 66% 1.0 mg/kg monthly (N=8) 66% 3.0 mg/kg monthly (N=8) 68% 3.0 mg/kg quarterly (N=4) 63% Pa
Slide 12: Pharmacodynamics: Plasma Oxalate Content in Part B
Lumasiran Phase 1/2 Study Initial Results* Pharmacodynamics: Plasma Oxalate Content in Part B (Patients with PH1) The mean reduction relative to baseline 28 days post last dose of lumasiran was 59% (N=10†) • Mean maximal reduction in plasma oxalate of 75% (range: 57-94%) relative to baseline after l
Slide 13: Pharmacodynamics: Plasma Glycolate in Part B
Lumasiran Phase 1/2 Study Initial Results* Pharmacodynamics: Plasma Glycolate in Part B (Patients with PH1) Consistent with the pharmacology of lumasiran and results from healthy volunteers in Part A1 of the study, plasma glycolate levels increased in patients with PH1 receiving lumasiran Clinical e
Slide 14: ILLUMINATE-A: Phase 3 Study of Lumasiran in Children and Adults with PH1
ILLUMINATE–A*: Phase 3 Study to Evaluate the Efficacy and Safety of Lumasiran in Children and Adults with Primary Hyperoxaluria Type 1 Now Enrolling 6-Month Double Blind Treatment Period 54-month Extension Period Patient population Lumasiran 2:1 Randomization Three monthly loading doses then N=30 ma
Slide 15: Summary and Planned Next Steps
Lumasiran Phase 1/2 Study Initial Results* Summary and Planned Next Steps Primary hyperoxaluria type 1 (PH1) is a devastating disease characterized by the overproduction of oxalate, which results in renal stone formation, nephrocalcinosis and progressive kidney failure, ultimately leading to multi-o
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