APOLLO Phase 3 Study of Patisiran Topline Results

Transcription

1 Leo Living with hattr Amyloidosis APOLLO Phase 3 Study of Patisiran Topline Results September 20, 2017

2 Agenda Welcome Christine Lindenboom Vice President, Investor Relations & Corporate Communications Introduction John Maraganore, Ph.D. Chief Executive Officer Disease Overview & APOLLO Results Akshay Vaishnaw, M.D., Ph.D. Executive Vice President of R&D Commercial Preparedness & Next Steps Barry Greene President Q&A Session 2

3 Alnylam Forward Looking Statements This presentation contains forward-looking statements, within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of There are a number of important factors that could cause actual results to differ materially from the results anticipated by these forwardlooking statements. These important factors include our ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of our product candidates; pre-clinical and clinical results for our product candidates; actions or advice of regulatory agencies; delays, interruptions or failures in the manufacture and supply of our product candidates; our ability to obtain, maintain and protect intellectual property, enforce our intellectual property rights and defend our patent portfolio; our ability to obtain and maintain regulatory approval, pricing and reimbursement for products; our progress in establishing a commercial and ex-united States infrastructure; competition from others using similar technology and developing products for similar uses; our ability to manage our growth and operating expenses, obtain additional funding to support our business activities and establish and maintain business alliances; the outcome of litigation; and the risk of government investigations; as well as those risks more fully discussed in our most recent quarterly report on Form 10-Q under the caption Risk Factors. If one or more of these factors materialize, or if any underlying assumptions prove incorrect, our actual results, performance or achievements may vary materially from any future results, performance or achievements expressed or implied by these forward-looking statements. All forward-looking statements speak only as of the date of this presentation and, except as required by law, we undertake no obligation to update such statements. 3

4 John Maraganore, Ph.D. Chief Executive Officer Introduction 4

5 Patisiran For Patients Living with hattr Amyloidosis Edgar Christina Sr. Edgar Jr. Leo Ron Sr. Sandie 5

6 RNAi Therapeutics New Class of Innovative Medicines Harness natural pathway Catalytic mechanism Silence any gene in genome Upstream of today s medicines Clinically proven approach 6

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8 Akshay Vaishnaw, M.D., Ph.D. Executive Vice President of R&D Disease Overview & APOLLO Results 8

9 Hereditary ATTR (hattr) Amyloidosis DESCRIPTION Orphan multi-system disease caused by mutant transthyretin (TTR) amyloid deposits in nerves, heart, GI tract, and other tissues PATIENT POPULATION* ~50,000 CNS worldwide Cardiovascular Ocular Nephropathy GI Significant morbidity and fatal within 2-15 years from symptom onset Autonomic neuropathy Peripheral sensory-motor neuropathy 9 Image based on Conceicao et al., J Peripher Nerv Syst, 2016;21:5 9 *Ando et al., Orphanet J Rare Dis, 2013; Ruberg et al., Circulation, 2012

10 Patisiran for hattr Amyloidosis Potential for Disease Modification by Reducing Pathogenic Protein Patisiran Therapeutic Hypothesis patisiran Production of mutant and wild type TTR hattr amyloidosis IV administration Phase 2 completed Unstable circulating TTR tetramers reduced Phase 2 Open-Label Extension (OLE) study completed Phase 3 completed APOLLO-OLE study ongoing Organ deposition of monomers, amyloid (β-pleated) fibril prevented, clearance promoted Fast Track Designation in U.S.; Orphan Drug Designation in U.S., EU, Japan Expanded Access Protocol (EAP) ongoing in U.S Neuropathy, cardiomyopathy Stabilization or improvement 10

11 2:1 RANDOMIZATION APOLLO Patisiran Phase 3 Study Design N=225 Patient Population hattr amyloidosis: any TTR mutation, FAP Stage 1 or 2 Neurological impairment score (NIS) of Prior tetramer stabilizer use permitted ClinicalTrials.gov Identifier: NCT Patisiran 0.3 mg/kg IV q3w or Placebo IV q3w Primary Endpoint Change in mnis+7 from baseline at 18 months Secondary Endpoints Norfolk QOL-DN NIS-weakness R-ODS 10-meter walk mbmi COMPASS-31 Patients who complete the study may be eligible for patisiran treatment on Phase 3 OLE study (APOLLO-OLE), ClinicalTrials.gov Identifier: NCT Endpoint Domain Reference Range Improvement mnis+7 Neuropathy points Negative change Norfolk QoL QoL points Negative change NIS-W Motor Strength points Negative change R-ODS Disability 0 48 points Positive change 10-MWT Ambulation (gait speed) meter/second (m/s) Positive change mbmi Nutritional status kg/m 2 x g/l Positive change COMPASS Autonomic Symptoms points Negative change

12 APOLLO Patisiran Phase 3 Study Topline Results Population and Baseline Characteristics APOLLO enrolled 225 patients Patients enrolled at 44 sites in 19 countries from North America, EU, Asia Pacific and Central/South America from Dec 13 Jan genotypes represented 43% V30M 57% nonv30m 56% with cardiac involvement Mean baseline mnis+7 = 78.8 (range: ) 12 Topline results presented 20 Sept 2017 and qualified by detailed study results to be presented at 1 st European ATTR Amyloidosis Meeting for Patients and Doctors, 2-3 Nov 2017, in Paris, France

13 APOLLO Patisiran Phase 3 Study: Topline Results Primary and Secondary Endpoints Primary Endpoint (18 mo.) p-value mnis x Secondary Endpoints (18 mo.) p-value Norfolk-QoL 1.10 x NIS-W 1.40 x R-ODS 4.07 x MWT 1.88 x mbmi 8.83 x COMPASS Topline results presented 20 Sept 2017 and qualified by detailed study results to be presented at 1 st European ATTR Amyloidosis Meeting for Patients and Doctors, 2-3 Nov 2017, in Paris, France

14 APOLLO Patisiran Phase 3 Study: Topline Results Subgroup Analyses Mean improvement in mnis+7 from baseline, compared to placebo, observed across all subgroup analyses, including: Age Sex Race Geographic Region Genotype Baseline NIS Score FAP Stage Previous Tetramer Stabilizer Use Cardiac Subgroup 14 Topline results presented 20 Sept 2017 and qualified by detailed study results to be presented at 1 st European ATTR Amyloidosis Meeting for Patients and Doctors, 2-3 Nov 2017, in Paris, France

15 APOLLO Patisiran Phase 3 Study: Topline Results Safety Safety Patisiran Placebo Adverse Events 96.6% 97.4% Serious Adverse Events 36.5% 40.3% Deaths 4.7% 7.8% Discontinuations from Treatment 7.4% 37.7% Discontinuations from Treatment due to AEs 4.7% 14.3% AEs in 10% of patients, seen more frequently in patisiran compared with placebo: Peripheral edema* Infusion related reactions* 29.7% 18.9% 22.1% 9.1% No evidence of safety signal with regard to platelets, renal function or liver enzyme elevations 15 *Generally mild-to-moderate in severity Topline results presented 20 Sept 2017 and qualified by detailed study results to be presented at 1 st European ATTR Amyloidosis Meeting for Patients and Doctors, 2-3 Nov 2017, in Paris, France

16 Barry Greene President Commercial Preparedness & Next Steps 16

17 Planned Next Steps for Patisiran APOLLO Detailed Results Nov 17 NDA Submission Late 17 MAA Submission Early 18 U.S. / EU Launch

18 Succeeding in Rare Disease Requires a Specific Road Map Engagement and Advocacy Educate Retain Diagnose RNAi Therapeutics Success Support and Solutions Access Best or First-in-Class Product Profiles 18

19 hattr Amyloidosis Market Landscape Limited available therapies; no approved drugs that halt disease progression and improve patient quality of life U.S.: No approved drugs; limited use of diflunisal off-label EU: tafamidis approved for Stage 1 polyneuropathy patients only; limited access (e.g., not reimbursed in UK) Multiple studies that document disease progression during tafamidis treatment 1-5 Orthotopic liver transplantation (OLT) use declining worldwide 6 Generally limited to younger patients with V30M mutation Involves significant risks and may still result in disease progression Contraindicated for patients with cardiomyopathy Few investigational therapies in clinical development Inotersen/NEURO-TTR Study Cortese et al. 1 N 61 Baseline NIS-LL 28 ± 5 Month 6 Month 12 Month (62% of patients) +5.9 (65% of patients) +8.0 (65% of patients) Randomized controlled trial in 61 patients with hattr Amyloidosis NIS-LL = neuropathy impairment score-lower limb Cortese A, et al. J Neurol 2016; 263: ; 2. Plante-Bordeneuve V, et al. J Neurol 2017; 264: Coelho T et al. Neurology 2012; 79:785-92; 4. Lozeron et al. Eu J Neurol 2013; 20: Merlini G, et al. J Cardiovasc Transl Res 2010; 6: Suhr O, et al. Transplantation 2016;100:

20 Alnylam to Commercialize in U.S. / Canada / W. Europe Collaboration with Sanofi Genzyme in Rest of World Patisiran to be commercialized by Alnylam in its territories Cambridge, MA Maidenhead, UK Zug, Switzerland Alnylam Sanofi Genzyme Note: Not to scale 20

21 Digital Educational Initiatives Recently launched two websites for disease education Health care professionals Patients and their families

22 Alnylam Act TM No-charge Third-party Genetic Testing and Counseling Program* Individuals with suspected diagnosis or confirmed family history of hattr amyloidosis eligible to take part in Genetic Screening performed by CLIA-certified clinical diagnostic laboratory Three testing options now available via saliva or blood Neuropathy Panel Cardiomyopathy Panel Single TTR Gene Testing >300 Accounts** ~2,000 Tests Submitted** More information regarding this program available at: Genetic counseling offered by genetics services provider Counseling available before, during or after genetic testing Exploring supported diagnostic program in EU 22 *Available in the United States Only **Since program inception and as of July 22, CLIA - Clinical Laboratory Improvement Amendments At no time does Alnylam receive patient-identifiable information.

23 23 Q&A Session

24 24 Thank You