Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — OxalEurope Meeting 2018
14 slides from Alnylam Pharmaceuticals's conference presentation, Jun 8, 2018
Slide 1: A Phase 1/2 Trial of Lumasiran (ALN-GO1) for Primary Hyperoxaluria Type 1
A Phase 1/2 Trial of Lumasiran (ALN-GO1), an Investigational RNAi Therapeutic for Primary Hyperoxaluria Type 1 OxalEurope Meeting | Naples, Italy| 8 June 2018 © 2018 Alnylam Pharmaceuticals, Inc.
Slide 2: Background: Primary Hyperoxaluria Type 1 (PH1)
Background Primary Hyperoxaluria Type 1 (PH1) Rare autosomal recessive disorder of increased endogenous oxalate synthesis due to defect in liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT) Phenotype varies from ESRD in infancy to occasional stone formation in adulthood Calcium oxala
Slide 3: Background: Current Therapeutic Approaches
Background Current Therapeutic Approaches No approved medical therapies Goal: Preservation of kidney function • Decreased oxalate production with Vitamin B6 (effective in minority of patients) • Decreased crystallization with high fluid intake, citrate Patients with ESRD • Increased oxalate removal
Slide 4: Lumasiran (ALN-GO1)
Lumasiran (ALN-GO1) Lumasiran is an investigational RNAi therapeutic targeting glycolate oxidase (GO) in development for treatment of Primary Hyperoxaluria Type 1 (PH1) Lumasiran is designed to reduce hepatic levels of GO enzyme (encoded by HAO1), thereby depleting substrate necessary for oxalate pr
Slide 5: Oxalate Synthesis in Hepatocytes
Oxalate Synthesis in Hepatocytes 6 Baker PR, et al. Am J Physiol Cell Physiol. 2004 Nov;287(5):C1359-65.
Slide 6: Part A Study Results: Plasma Glycolate Levels in Healthy Volunteers
Lumasiran Phase 1/2 Part A Study Results: Plasma Glycolate Levels in Healthy Volunteers Dose-dependent increase in plasma glycolate levels in healthy volunteers after single dose of lumasiran1 Treatment Group: Placebo (N=8) ALN-GO1 0.3 mg/kg (N=6) ALN-GO1 1.0 mg/kg (N=6) ALN-GO1 3.0 mg/kg (N=6) ALN-
Slide 7: Reported Cases of Known or Suspected GO Inactivity
Reported Cases of Known or Suspected GO Inactivity Lumasiran targets GO, key enzyme in pathway of hepatic oxalate production. Many patients with PH1 already have elevated glycolate levels as part of their disease pathophysiology. No known negative impact of elevated glycolate levels. 8 year old boy1
Slide 8: Study Design & Demographics: Part B (Patients with PH1)
Lumasiran Phase 1/2 Study* Study Design† & Demographics: Part B (Patients with PH1) Multiple-Ascending Dose (MAD) │ Randomized 3:1, Single-blind, Placebo-controlled 1.0 mg/kg, q28d x 3 SC, N=4 3.0 mg/kg, q28d x 3 SC, N=4 3.0 mg/kg, q84d x 2 SC, N=4 Expansion Cohorts │ Open-label 1.0 mg/kg, q28d x 3
Slide 9: Patient Demographics & Exposure: Part B (Patients with PH1)
Lumasiran Phase 1/2 Study* Patient Demographics & Exposure: Part B (Patients with PH1) Characteristic 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) *Data as of: March 29
Slide 10: Safety: Part B (Patients with PH1)
Lumasiran Phase 1/2 Study Initial Results* Safety: Part B (Patients with PH1) Multiple doses of lumasiran well tolerated in patients with PH1 75% of patients (n=15) with PH1 reported at least one adverse event (AE) • No AEs led to study discontinuation • Most AEs were mild or moderate in severity an
Slide 11: Pharmacodynamics: Part B (Patients with PH1)
Lumasiran Phase 1/2 Study Initial Results* Pharmacodynamics: Part B (Patients with PH1) Mean maximal reduction in urinary oxalate of 64% relative to baseline after lumasiran dosing in patients in Cohorts 1-3 (n=12) • Mean reduction in urinary oxalate of 63% relative to baseline was observed at study
Slide 12: Significance of Decreasing Urinary Oxalate
Significance of Decreasing Urinary Oxalate Lumasiran lowered UOx below 0.7 mmol/24hr/1.73m2 in all patients, including patients with baseline levels ≥ 1.6 mmol/24hr/1.73m2 Renal survival was examined by quartile of urine oxalate (UOx) excretion (mmol/24hr/1.73m2 ) at diagnosis of patients enrolled i
Slide 13: Summary and Next Steps
Lumasiran Phase 1/2 Initial Study Results* Summary and Next Steps Lumasiran (ALN-GO1) is a subcutaneously administered investigational RNAi therapeutic designed to reduce hepatic production of oxalate in patients with Primary Hyperoxaluria Type 1 (PH1) Multiple doses of lumasiran have been well tole
Slide 14: Acknowledgements
Acknowledgements Thank you to the patients, investigators, and study staff who participated in these studies ALN-GO1-001 Investigators Reham Almardini Jérôme Harambat Ulrike Lorch Pierre Cochat Bernd Hoppe Daniella Magen George Deschenes Sally-Anne Hulton Dawn Milliner Yaacov Frishberg John Lieske S