First Quarter 2017 Financial Results

Transcription

1 Colin Living with Porphyria First Quarter 2017 Financial Results May 5,

2 Agenda Welcome Christine Regan Lindenboom Vice President, Investor Relations & Corporate Communications Q Overview John Maraganore, Ph.D. Chief Executive Officer Alnylam Clinical Pipeline Akshay Vaishnaw, M.D., Ph.D. Executive Vice President of R&D Financial Results Michael Mason Vice President, Finance and Treasurer 2017 Goals Update 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 annual report on Form 10-K 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 Q Overview 4

5 Strategic Context for 2017 APOLLO Phase 3 topline results expected in mid-2017 If positive, plan to file NDA/MAA at year-end Expect to advance three additional programs into Phase 3 studies Fitusiran, for the treatment of hemophilia Givosiran, for the treatment of acute hepatic porphyrias Inclisiran, for the treatment of hypercholesterolemia (in collaboration with The Medicines Company) Building world-class team and capabilities in preparation for potential transition to commercial stage Includes Quality, Medical Affairs, Manufacturing, and Commercial teams Buildup in North America and Western Europe, and then Global 5

6 Akshay Vaishnaw, M.D., Ph.D., Executive Vice President of R&D Alnylam Clinical Pipeline 6

7 Alnylam ATTR Amyloidosis Portfolio Committed to Continued Innovation for Patients Patisiran IV administration Phase 2 completed Phase 3 trial ongoing; fully enrolled with topline results expected in mid APOLLO-OLE study ongoing ALN-TTRsc02 ESC second generation chemistry Anticipate quarterly SC dose regimen Phase 1 ongoing; initial positive data presented December

8 ΔmNIS+7 from baseline to Month 24 Mean (SEM) ΔmNIS+7 from baseline at 24 mos~ Natural History Placebo (N=66) Diflunisal (N=64) Patisiran Phase 2 OLE Final Study Results Change in mnis+7 at 24 Months out of 27* patients (74%) with no change or an improvement in mnis+7 at month 24 compared to baseline (9.4) 29.6 (3.1) (2.7) (nonlinear; N=283) 1# // Diflunisal Ph 3 Study 2+ // Patisiran Ph 2 OLE^ (N=26) -7.0 (2.0) Individual ΔmNIS+7 at Month 24 (n=26) Adams et al., AAN, April 2017; SEM: Standard Error of the Mean; *One patient discontinued prior to the Month 24 assessment and is included in the denominator ~Assessments drawn from studies in patients with similar baseline neurologic impairment and not based on head-to-head studies #Predicted progression of median NIS value from Gompertz curve fit 1 +Linear interpolation from 2-year NIS progression measurement in longitudinal analysis set ^Patisiran results similar in patients with/without concurrent TTR stabilizer therapy; mnis+7 using full mnis+7 set; partial imputation was used to recover mnis+7 data points where components were missing at one or more replicate measurements (per patient/visit) 1. Adams D et al. Neurology. 2015;85; Berk JL et al. JAMA. 2013;310: Mean ΔmNIS+7 Across hattr Amyloidosis Studies at 24 mos ~

9 Patisiran Phase 2 OLE Final Study Results Change in mnis+7 at 24 Months by Baseline NIS Tertile 9Change in mnis+7 from Baseline to Month Individual ΔmNIS+7 at Month 24 (n=26) 0 27 Baseline NIS Tertiles N Baseline NIS Range Mean (SEM) ΔmNIS+7 from Baseline to Month 24 First Tertile (2.0) Second Tertile (3.3) Third Tertile (4.3) SEM: Standard Error of the Mean Adams et al., AAN, April 2017

10 Mean Absolute Change from Baseline in Dermal Amyloid Content, % Patisiran Phase 2 OLE Final Study Results TTR Amyloid Content in Skin: Lower Limb Blinded analysis of tandem skin punch biopsies performed at central lab; statistical significance testing performed post-hoc Dermal amyloid content in both distal thigh and distal leg decreased over time relative to baseline Statistically significant decrease in absolute change for distal thigh at 6, 18 and 24 months and at all time points for distal leg 0 Mean Absolute Change from Baseline in Dermal Amyloid Content 6 months 12 months 18 months 24 months Median Relative Change from Baseline in Dermal Amyloid Content Distal Thigh N Median Relative Percent Change (IQR) Distal thigh dermal amyloid content in Patient months (-75.7, 0) * N= * N=22 N= * N= * N=20 Distal Thigh (Baseline Amyloid content (n=24): 10.9%) Distal Leg (Baseline Amyloid content (N=24): 15.8%) * N= * N= * N=19 12 months (-87.5, 0) 18 months (-89.7, -8.3) 24 months (-78.3, 0) Distal Leg N Median Relative Percent Change (IQR) 6 months (-74.3, 0) 12 months (-85.8, 0) 18 months (-91.3, -10) 24 months (-78.3, -21.6) Baseline * P<0.05 IQR, Interquartile Range; 1 patient excluded due to baseline value of 0 and a non-zero post-baseline value 24months Red: Amyloid by Congo red staining 10 Adams et al., AAN, April 2017

11 Patisiran Phase 2 OLE Final Study Results Summary Patisiran generally well tolerated in patients with hattr amyloidosis out to 25 months No drug-related SAEs and majority of AEs were mild or moderate Drug-related AEs reported in 4 patients were infusion related reaction (22.2%) and flushing (22.2%), all of which were mild Results consistent with therapeutic hypothesis that patisiran can potentially halt or improve neuropathy progression Long-term patisiran administration resulted in improvement in neuropathy impairment score with mean 7.0-point decrease in mnis+7 at 24 months Compares favorably to expected mean point increase in mnis+7 at 24mo estimated from analyses of separate historical data sets in untreated hattr patients with similar baseline neuropathy impairment Improvement or no change in mnis+7 observed in 20 of 27 (74%) patients In exploratory analyses, observed an increase in sweat gland nerve fiber density and a decrease in dermal amyloid content in the distal thigh and leg relative to baseline All eligible patients have enrolled into the APOLLO-OLE study and will continue to receive patisiran dosing As of May 5, 2017, more than 20 patients received 36 months of patisiran dosing; plan to present data in late 2017 Plan to present APOLLO Phase 3 topline results in September 11

12 AT Activity (%) Fitusiran for Hemophilia Potential to Restore Hemostasis in Hemophilia Genetically validated, liver-expressed target gene Biomarker for POC in Phase 1 Definable path to approval and patient access Hemophilia A FVIII Hemophilia B FIX FVIIIa FIXa FXa Prothrombin FVIIa FVII FX AT AT FVa FV Thrombin Fibrinogen Fibrin Blood clot Plasma Biomarkers AT Lowering, Thrombin Generation AT % Lowering Peak Thrombin Days Fitusiran Phase 1 results: Pasi et al., WFH, July Peak Thrombin (nm) Established Endpoint Annualized Bleeding Rate (ABR) Photo courtesy of Guy Young, M.D. Director, Hemostasis & Thrombosis Center at Children's Hospital Los Angeles and Professor of Pediatrics, USC Keck School of Medicine

13 2:1 2:1 Preliminary Fitusiran ATLAS Phase 3 Program* Plan to Initiate in Early 2017 Adults and adolescents with hemophilia A or B with inhibitors On-demand N~50 Fitusiran OR OD BPA Endpoints: ABR Bypassing agent (BPA) consumption Quality of life Safety Adults and adolescents with hemophilia A or B without inhibitors On-demand N~100 Fitusiran OR OD Factor Endpoints: ABR Factor VIII or IX consumption Quality of life Safety Adults and adolescents with hemophilia A or B with or without inhibitors Prophylaxis N~100 PPX Factor/BPA Fitusiran Endpoints: ABR Factor/BPA consumption Quality of life Safety All completers will be eligible for fitusiran treatment in Phase 3 OLE study (ATLAS-OLE) 13 *Preliminary plans subject to further diligence and health authority feedback

14 Acute Hepatic Porphyrias DESCRIPTION Family of ultra-rare orphan diseases causing incapacitating and potentially fatal attacks PATIENT POPULATION* with sporadic attacks ~5,000Patients in U.S./EU with recurrent attacks ~1,000Patients in U.S./EU Disease burden includes: - Acute, Severe Abdominal Pain - Frequent Hospitalizations - Peripheral and Autonomic Neuropathy - Neuropsychiatric Symptoms - Chronic Pain Predominantly female, commonly misdiagnosed 14 *ORPHANET; The Porphyria Consortium

15 Mean (SEM) % ALA Knockdown Givosiran for Acute Hepatic Porphyrias Potential to Prevent Debilitating Attacks EMA PRIME Designation Genetically validated, liver-expressed target gene Biomarker for POC in Phase 1 Definable path to approval and patient access ALAS1 upstream of genetic defect Serum and Urinary Biomarkers ALA and PBG Placebo mg/kg 0.1 mg/kg 0.35 mg/kg 1.0 mg/kg 2.5 mg/kg Potential Endpoints Annualized attack rate ALA and PBG levels 0 20 Up-regulation of ALAS Accumulation of toxic intermediates ALA and PBG Time (Months) Givosiran Interim Phase 1 results: Sardh et al., ASH, December 2016

16 Robust and Sustained LDL-C Reductions with Inclisiran* Phase 2 Results to Day 270 Following Two Doses Safety (N=501): No drug-related SAEs, no discontinuations due to AEs Two patient deaths due to MI and stroke, both unrelated to study drug No LFT elevations related to study drug Majority of AEs mild or moderate in severity PLANNED NEXT STEPS FOR INCLISIRAN: Start Phase 3 study in mid *Phase 2 study results; Ray et al., ACC, March 2017; Inclisiran also known as ALN-PCSsc and PCSK9si The Medicines Company is leading and funding development of inclisiran from Phase 2 onward and will commercialize the program, if successful

17 Other Programs to Watch ALN-CC5 for Complement-Mediated Diseases ALN-HBV for Hepatitis B Virus (HBV) Infection Sustained control of disease hemolysis with up to 67% reduction in eculizumab dose in PNH patients 1 ALN-GO1 for Primary Hyperoxaluria 1 (PH1) Pre-clinical results: 3 up to 3.6 log 10 HBsAg reduction Safety (N=6): No SAEs, no discontinuations due to AEs 1 AE of hemolysis in setting of URI; moderate in severity and considered unrelated to study drug 1 AE of asymptomatic, transient grade 3 elevation of LFTs; considered possibly related Up to 8-fold increase in plasma glycolate in healthy volunteers 2 Safety (N=32): No SAEs, no discontinuations due to AEs All AEs mild or moderate, with exception of one subject with transient, asymptomatic CPK elevation considered unrelated to study drug RECENT ACTIVITY FOR ALN-GO1: First PH1 Patient Dosed in March Phase 1/2 Study; Hill et al., ASH, Dec Phase 1/2 Study; Milliner et al., IPNA, Sep Mouse model; Sepp-Lorenzino et al., Liver Meeting, Nov 2015

18 Michael Mason Vice President, Finance and Treasurer Q Financial Results 18

19 Financial Summary and Guidance 2017 Q1 Financial Results Cash $962.2M Includes $150.0M in restricted investments GAAP Revenues $19.0M Total GAAP Operating Expenses $125.5M Research and Development Expense $87.0M General and Administrative Expense $38.5M GAAP Net Loss of $107.3M Shares Outstanding 86.1M 2017 Guidance Year-end cash >$700M Includes $150.0M of restricted investments 19

20 Barry Greene President 2017 Goals Update 20

21 Transition to Potential Commercialization Planned Rapid Launch Succession Givosiran ~2020 Fitusiran ~2019 Patisiran ~2018 Manufacturing build-out to ensure consistent drug supply underway Alewife facility fully operational and ready for patisiran launch Norton drug substance facility expected to be commercially operational in 2020 Building commercial capabilities to prepare for potential product launches Patisiran in US, Canada, and Western Europe Fitusiran co-develop/co-commercialize in US, Canada, and Western Europe Givosiran globally 21

22 Alnylam 2017 Pipeline Goals *Early is Q1-Q2, Mid is Q2-Q3, and Late is Q3-Q4 PATISIRAN (hattr Amyloidosis) Phase 2 OLE data APOLLO Phase 3 top-line APOLLO Phase 3 results NDA/MAA filing 2017* Early Mid Late FITUSIRAN (Hemophilia and RBD) GIVOSIRAN (Acute Hepatic Porphyrias) Phase 2 OLE data ATLAS Phase 3 program start Phase 1, Part C data Phase 3 study start ORION-1 Phase 2 data INCLISIRAN** (Hypercholesterolemia) ADDITIONAL CLINICAL PROGRAMS ORION-2 HoFH study start ORION-3 Phase 2 OLE study start ASCVD Phase 3 study start Continue to advance early/mid-stage pipeline; Present clinical data **Based on The Medicines Company guidance as of January

23 Q Financial Results Q&A Session 23

24 24 Thank You