Alnylam Pharmaceuticals, Inc. · NASDAQ:ALNY
Alnylam Pharmaceuticals — Technical Presentation (July 2017)
16 slides from Alnylam Pharmaceuticals's technical presentation, Jul 10, 2017
Slide 1: Fitusiran, an Investigational RNAi Therapeutic Targeting Antithrombin: Interim Phase 2 Extension Results
Venkat Venkat Living with Hemophilia Living with Hemophilia Fitusiran, an Investigational RNAi Therapeutic Targeting Antithrombin for the Treatment of Hemophilia: Interim Results from a Phase 2 Extension Study in Patients with Hemophilia A or B with and Without Inhibitors K John Pasi, Pencho Georgie
Slide 2: Fitusiran: Investigational RNAi Therapeutic for Treatment of Hemophilia
Fitusiran Investigational RNAi Therapeutic for Treatment of Hemophilia Fitusiran (ALN-AT3) • SC-administered small interfering RNA (siRNA) therapeutic Hemophilia A targeting antithrombin (AT) FVIIa FVII FX ◦ Non-biologic, chemically-synthesized, with targeting ligand to FVIII FVIII FVIIIa specifical
Slide 3: Fitusiran Phase 2 OLE Study Design & Patient Disposition
Fitusiran Phase 2 Open-Label Extension (OLE) Study Design & Patient Disposition Patients previously dosed in Phase 1* study eligible to roll over onto Phase 2 OLE^ study Phase 1, Part B (N=12 patients with HA or HB) 15, 45, 75 mcg/kg weekly x 3 SC Phase 2 OLE‡ (n= 33) Phase 1, Part C (N=18 patients
Slide 4: Patient Demographics & Exposure
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Patient Demographics & Exposure Patients without Inhibitors Patients with Inhibitors 50 mg† 80 mg† 50 mg† 80 mg† N=10 N=9 N=3 N=11 Age, years; mean (range) 36 (19 – 61) 40 (24 – 58) 31 (22 – 36) 34 (21 – 41) Weight, kg; mean (range)
Slide 5: Patient Disposition
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Patient Disposition 33 Patients Enrolled 5 Patients Discontinued Dosing • 4 due to withdrawal of consent† • 1 due to AE‡ 28 Patients Continued Dosing *Data transfer 15June2017 AE, adverse event † Withdrawal of consent due to: incarc
Slide 6: Safety/Tolerability
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Safety/Tolerability • 6 patients reported SAEs† ◦ 2 with SAEs considered possibly related to study drug – Asymptomatic ALT and AST elevation in patient with chronic HCV infection; led to discontinuation – Seizure with confusion in p
Slide 7: Context for Transaminase Elevations
Slide not included in presentation given at ISTH 2017 Context for Transaminase Elevations Fitusiran is a liver-directed therapy and low frequency of ALT changes with other molecules in our platform have been reported However, chronic HCV infection has been associated with elevated ALT and thus repre
Slide 8: Antithrombin Levels and Thrombin Generation
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Antithrombin Levels and Thrombin Generation Antithrombin Levels Thrombin Generation 1.0 50 mg monthly (N=13) 135 50 mg monthly (N=13) 0.9 80 mg monthly (N=20) HV Median‡ 80 mg monthly (N=20) 120 Mean [+/- SEM] Thrombin Generation Me
Slide 9: Exploratory Analysis of Bleed Events
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Exploratory Analysis of Bleed Events Summary of Median ABRs in all Patients • 48% (16/33) of patients bleed free during observation period† ◦ Overall median ABR in observation period = 1 (IQR: 0-3) • 67% (22/33) of patients reported
Slide 10: Characteristics of Bleed Events During Treatment with Fitusiran
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Characteristics of Bleed Events During Treatment with Fitusiran Bleed events evaluated in patients when antithrombin lowering was >75% Characteristic Patients without Inhibitors (n=19) Patients with Inhibitors (n=14) Total bleeds, n
Slide 11: Management of Bleed Events with Factor Replacement in Patients without Inhibitors
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Management of Bleed Events with Factor Replacement in Patients without Inhibitors* Treatment of Bleeds FVIII (n=8) FIX (n=2) No more than 30 IU/kg; re-dose after 24 No more than 50 IU/kg; re-dose after 24 Recommendation from Protoco
Slide 12: Management of Bleed Events with Bypassing Agents in Patients with Inhibitors
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Management of Bleed Events with Bypassing Agents in Patients with Inhibitors* Treatment of Bleeds aPCC (n=4) rFVIIa (n=1) Up to 75 U/kg for minor to moderate bleeds Up to 90 μg/kg every 2 hours, adjustable and up to 100 U/kg (no mor
Slide 13: Summary
Interim Fitusiran Phase 2 Open-Label Extension (OLE) Study Results* Summary Increasing patient safety experience, with up to 20 months of dosing in Phase 2 OLE • Majority of AEs were mild or moderate in severity; ISRs most common non-laboratory AE, all mild and transient • No thromboembolic events;
Slide 14: Modeling Based on Clinical Data Supports 80 mg as Phase 3 Dose
Slide not included in presentation given at ISTH 2017 Next Steps Modeling Based on Clinical Data Supports 80 mg as Phase 3 Dose Simulation of mean ABR as a function of AT Modeled Dose-AT Relationship suggests a target of ~80% AT lowering 50 100 100 P r e d ic t e d S t e a d y -S t a t e Predicted S
Slide 15: Next Steps: ATLAS Phase 3 Program Initiated
Slide not included in presentation given at ISTH 2017 Next Steps ATLAS Phase 3 Program Initiated • Adults and adolescents with Primary Endpoints: 9 months hemophilia A or B with • ABR† fitusiran inhibitors Secondary Endpoints: 2:1 • Currently manage bleeds OR • Spontaneous ABR with on-demand bypassi
Slide 16: Acknowledgements
Acknowledgements Thank you to the patients, investigators, and study staff who participated in these studies Country PI Name Location United Kingdom Steve Austin London – St. George’s Healthcare NHS Trust Haemophilia Centre David Bevan London – The Centre for Haemostasis and Thrombosis Guy’s and St.
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