The Medicines — Medicines — Investor Day (November 2014)
183 slides from The Medicines's investor day presentation, Nov 5, 2014
Slide 1: Investor & Analyst Day
INVESTOR & ANALYST DAY The Roosevelt Hotel, New York 5 November 2014 the medicines company
Slide 2: Welcome
Welcome Bob Laverty The Medicines INVESTOR & ANALYST Welcome Bob Laverty The Medicines
Slide 3: Legal notices: forward looking statements
3 Statements in this presentation about The Medicines Company (the “Company”), the Company’s products and product candidates, the timing of clinical trial results, regulatory submissions, product or indication launches, the Company’s strategy, future financial results and operations, and future oppo
Slide 4: Program overview agenda
4 I Q&A II Q&A III Q&A IV 08:30 09:00 09:30 10:00 10:30 11:00 11:30 12:00 12:30 Program overview Agenda 08:30–12:30 I Growth drivers today II Growth drivers ahead III Business strategy IV What’s next
Slide 5: Overview
Overview Clive Meanwell The Medicines Company Overview Clive Meanwell The Medicines Company
Slide 6: One year ago we described
6 One year ago we described: Purposeful approach to the acute and intensive hospital care market Intellectual property program with ANGIOMAX® Four intended product launches in three hospital care pathways Our intention to add more products that fit our strategy Since that time we have: Moved forward
Slide 7: One year ago: portfolio for three hospital care pathways
7 One year ago Portfolio set up to serve three hospital care pathways Acute Cardiovascular Surgery & Perioperative Infectious Disease Market ANGIOMAX®/ANGIOX® BRILINTA®* RECOTHROM® CLEVIPREX® HTN Argatroban, 50 mg per 50 mL† NDA Cangrelor IONSYS™ RAPLIXA™ ORBACTIV™ ABSSSI R&D CLEVIPREX® AHF MDCO-216
Slide 8: Today: portfolio expanded
8 Today, 12 months later Portfolio expanded Acute Cardiovascular Surgery & Perioperative Infectious Disease Market ANGIOMAX®/ANGIOX® BRILINTA®* Promus PREMIER™ stentII CLEVIPREX® HTN RECOTHROM® Argatroban, 50 mg per 50 mL† PREVELEAK™ ORBACTIV™ MINOCIN® IV NDA Cangrelor IONSYS™ RAPLIXA™ ORBACTIV™ (EU
Slide 9: Major regulatory activities during the last months
9 Major regulatory activities during the last 12 months Asset United States Europe ORBACTIV™ NDA approved, launched MAA review on track Cangrelor CRL resubmission MAA review on track (planned Q4) RAPLIXA™ NDA review ext. to 4/15 MAA review on track IONSYS™ NDA review on track MAA review on track Str
Slide 10: Asset acquisitions during the last months
10 Asset acquisitions during the last 12 months Asset United States Europe MINOCIN® IV Acquired, re-launched MINOCIN® IV new formuln Acquired, sNDA on track MAA plan accepted (RPX-602) CARBAVANCE™ Acquired, Phase 3 started MAA plan accepted BARDA contract up to $90M Range of BLI programs Acquired, I
Slide 11: Progress towards proof of clinical concept
11 Progress towards proof of clinical concept during the last 12 months Asset Progress MDCO-216 (ApoA1-M) Mechanism, cholesterol efflux, and safety (humans) Manufacturing scale-up feasibility and construction PCSK9 synth. inhibitor Clinical effect and preliminary safety of IV formuln (humans) (with
Slide 12: Strategy for growth
12 Strategy for growth Innovation: Strategic and operating leverage Situation Strategy Actions 1 Customers demand value Lead with purpose Build value-based solutions 2 Near term growth demand Launch new products strongly Emphasize US market 3 ANGIOMAX® IP complexity Steadfast commitment Manage litig
Slide 13: Investor & Analyst Day objectives
13 Describe progress, status and plans, focusing on: Marketed growth drivers today ORBACTIV™ and MINOCIN® IV PREVELEAK™ ANGIOMAX® Growth drivers ahead—under regulatory review RAPLIXA™ IONSYS™ Cangrelor Growth drivers ahead—at or approaching clinical proof of concept ApoA1-Milano cholesterol efflux p
Slide 14: Growth drivers today
Growth drivers today Clive Meanwell The Medicines Company
Slide 15: What hospitals want
What hospitals want Mike Jellinek Lahey Health System
Slide 16: Current Issues in US Hospitals
Current Issues in US Hospitals Michael Jellinek, M.D. CEO, Community Network EVP, Lahey Health System Burlington, MA November 5, 2014
Slide 17: Mission
Mission • Care for every patient like a beloved family member – Safe, high quality, coordinated care • Exceed patient’s and family’s expectations • Relentless pursuit of excellence • Teaching standard – “Do it the way you would teach it.” • Academic medical center – Teach – Research
Slide 18: Market Forces Vary
Market Forces Vary • All fee for service—18% of GDP, slope? • Commercial vs. Medicare vs. Medicaid • Universal coverage vs. indigent care burden • Competition: – Hospital, physicians and for-profit, technical and ancillary services • Population health management/holding risk (lower utilization, infr
Slide 19: Financial Pressures
Financial Pressures • Fixed cost structure, 24 x 7, full service – Ready for anything—Ebola, flu, fire, bus accident, – Bullet wound, heart attack • 60% + labor expense • Heavily regulated, high standards • IT investment (EPIC) • AMC—teaching/research requires subsidy • Pension costs • Most services
Slide 20: Utilization Critical
Utilization Critical • Hospital margin range . Most low (0 to 4%) • 80% plus utilization to cover fixed costs • Fee for service—incentive to utilize but: • Inpatient to outpatient (gall bladder, hip) • Length of stay down, more admissions • Co-pays and high deductibles decrease and steer patients •
Slide 21: Management Responses
Management Responses • Growth: volume in fee for service; covered lives in HPM (costly investments) • Constrain capital (age of plant, bond rating) • Wage increases limited; lower benefit costs • Process improvement • Supply chain; standardization • Review costly new technology • Pharmacy management
Slide 22: Likely Future
Likely Future • Right care in right place at right time • Value based purchasing—quality outcome at lower cost • Process improvement, standardization • Focus on patient experience... satisfaction • Population health management consolidation, integrate insurance and provider • Movement to outpatient
Slide 23: Launching new antibiotics: ORBACTIV and MINOCIN IV
Launching 2 new antibiotics: ORBACTIV™ and MINOCIN® IV Mike McGuire, Michael Mitchell The Medicines Company
Slide 24: SOLO I data support outpatient treatment option
24 Efficacy and safety of single dose oritavancin compared to 7–10 days of vancomycin in patients with acute bacterial skin and skin structure infections treated in outpatient setting.” K. LaPensee, W. Fan, H. Jiang, T. Lodise New data presented at ICAAC SOLO I data support outpatient treatment opti
Slide 25: Early clinical response methods and results
25 Early clinical response was assessed at 24–48 hours. Methods and results SOLO I data support outpatient treatment option ORBACTIV™ Vancomycin N ECE N ECE Hospital 303 82.2 306 80.7 Outpatient 172 82.6 173 75.7 LaPensee K, Lodise TP, Fan W, et al. Comparison of Efficacy and Adverse Events between
Slide 26: Resources applied and team is built
26 Resources applied and team is built Experienced customer facing team in place consisting of customer engagement, market access and global health science Category Average years of experience ID 5.5 Hospital 13.9 GHSC Clinical practice/academia 10.2 Pharmaceutical industry 9.9 I Growth drivers toda
Slide 27: Many customers have waited for ORBACTIV availability
27 Many customers have waited for ORBACTIV™ (oritavancin) availability: There are formulary reviews scheduled over next three months 1,451 Hospitals* *Total number of hospitals MDCO calls on in the US. I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of
Slide 28: Core accounts targeted
28 1,451 Hospitals 1,008 Core accounts* *Hospitals targeted by MDCO’s Infectious Disease Care team. I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostasis in surgery PCI patients ANGIOMAX® IP II Growth
Slide 29: Active discussions
29 1,451 Hospitals 827 Active discussions 1,008 Core accounts I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostasis in surgery PCI patients ANGIOMAX® IP II Growth drivers ahead III Business strategy IV
Slide 30: Active discussions with core accounts
30 1,451 Hospitals 827 Active discussions 607 Active discussions (with core accounts) 1,008 Core accounts I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostasis in surgery PCI patients ANGIOMAX® IP II G
Slide 31: Formulary reviews expected over next three months
31 827 Active discussions 607 Active discussions (with core accounts) 300 Reviews expected over next three months 1,008 Core accounts 1,451 Hospitals I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostas
Slide 32: System case study
32 System case study Large academic teaching institution Current ABSSSI pathway Diagnosis: ED Treatment: IV antibiotic patients admitted Hospitalist calls ID consult if severe Patient discharged to OP infusion Economics: Costs are ~$1M higher than reimbursement New pathway Observation unit being con
Slide 33: Hospital case study
33 Hospital case study Small community hospital Current ABSSSI pathway Diagnosis: Majority in ED Treatment: Admitted by hospitalist 200 ABSSSI per year Economics: Costs are $500–$1500 per patient higher than reimbursement New pathway ORBACTIV™ OPAT only ID restriction short term Long-term goal to op
Slide 34: Outpatient case study
34 Outpatient case study ID owned infusion center Current ABSSSI pathway Diagnosis: Referrals Treatment: Direct referral from MD • 3–6 days to complete therapy Hospital discharge referrals • 7–10 days IV OPAT Up to 2 hours drive time New pathway Direct referrals treated by single infusion Hospital d
Slide 35: MINOCIN IV
MINOCIN®* IV
Slide 36: MINOCIN IV case study
36 MINOCIN® IV (minocycline for injection) case study Large academic teaching center in the central US For MINOCIN® IV indication and Important Safety Information, please see www.minociniv.com. Multidisciplinary institution serving a large geographic area Over 40,000 patients admitted a year for man
Slide 37: Early experience with minocycline
37 Jankowski C. et al. Infectious Diseases in Clinical Practice. 2012;Volume 20;Issue 3;184–187. Early experience with minocycline Demographics and clinical outcomes of patients with Acinetobacter baumannii infections treated with minocycline IV ID Age, Gender Site of infection (hospital day culture
Slide 38: New acinetobacter burden of illness data
38 ID week: New acinetobacter burden of illness data MDR is prevalent: Mortality, health service utilization, costs high MDR Non-MDR Prevalence 74.1% 25.9% Mortality 15.3% 5.9% LOS (days) 13.4 10.5 Cost (mean) $32,086 $24,367 K. LaPensee et. al. Prevalence, Mortality and Outcomes of Antibiotic Thera
Slide 39: RPX-602 new formulation of MINOCIN IV
39 Being developed to help facilitate ease of use • Allows smaller administration volume at a more physiologic pH • Current formulation pH is 2.5–4.01, new formulation will be at 4.5–6.02 • Can infuse doses in a smaller volume where larger fluid volumes may be problematic Expect sNDA filing in 4Q 20
Slide 40: Summary ORBACTIV
40 Summary ORBACTIV™ Many hospitals delayed formulary process until ORBACTIV™ availability Experienced customer-facing organization in place Early formulary wins and usage reflect positive response to value pricing and data Anticipated events—4Q ISPOR EU—Budget impact model • Poster presentation I G
Slide 41: Summary MINOCIN IV
41 Summary MINOCIN® IV MINOCIN® IV is a safe and effective treatment for MDR acinetobacter infections1 MINOCIN® IV use is expected to increase in target ORBACTIV™ institutions Anticipated events—4Q sNDA submission for new formulation 1. MINOCIN® IV Prescribing Information. I Growth drivers today Wha
Slide 42: Pain in hospital: IONSYS
Changing the management of pain in hospital: IONSYS™ Jason Campagna, Jim Jones The Medicines Company
Slide 43: Disruptive innovation: state-of-the-art technology
44 Disruptive innovation State-of-the-art technology future: Reduced to the essential IONSYS™ is currently not approved for commercial use in any market. I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemo
Slide 44: Human factor studies
45 1 2 3 4 Ease of assembly Assembly instructions clarity Ease of application Application instructions clarity Overall ease of use Nurse assessment of patient understanding Nurse assessment of patient competence Disruptive innovation The human touch Human Factor studies for sNDA • Six studies submit
Slide 45: IONSYS performance
46 Disruptive innovation IONSYS™ (fentanyl iontophoretic transdermal system) performance Previous one part system: • <3% failure rate • Approved by FDA and EMA, and launched in Europe • 15,000 units sold in northern Europe in first six months Current two part system failure rate <0.2% (>4,000 system
Slide 46: IONSYS matches pharmacokinetics of IV fentanyl
47 Disruptive innovation IONSYS™ matches the pharmacokinetics of IV fentanyl Randomized cross-over design of 40 evaluable patients Patients received 80 µg of fentanyl over 20 minutes every hour for up to 24 hours • IONSYS™ • IV fentanyl infusion In consultation with FDA, identical design used in app
Slide 47: Patient global assessment: excellent response
48 Evaluable patients from four Phase 3 studies Study Morphine IV PCA n/N (%) IONSYS™ n/N (%) Odds Ratio (95% CI) IONSYS™ vs. Morphine IV PCA P-value All Studies 24 hr 454/1298 (35.0) 574/1271 (45.2) 1.533 (1.307, 1.798) <0.0001 All Studies 48 hr 308/818 (37.7) 467/827 (56.5) 2.196 (1.798, 2.683) <0
Slide 48: Adverse events versus morphine IV PCA
49 I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostasis in surgery PCI patients ANGIOMAX® IP II Growth drivers ahead III Business strategy IV What’s next Treated patients, AE onset after start of trea
Slide 49: Nurses and physical therapists found IONSYS easy to use
50 Overall ease of care Weighted Mean Difference Type of EOC Morphine IV PCA (N) IONSYS™ (N) Weighted Mean Difference (95% CI) P-value Nurses 702 722 0.57 (0.64, 0.50) <.0001 Physical Therapist 245 250 0.29 (0.41, 0.17) <.0001 Disruptive innovation Nurses and physical therapists found IONSYS™ easy t
Slide 50: Investing in the patient experience in pain management
51 Disruptive innovation Investing in the patient experience in pain management Patient satisfaction is one of the components of hospital reimbursement Pain is 1 of 8 total dimensions being measured by HCAHPS Quality improvement efforts around pain are declining 1. Abraham, J. (2014, June). An Analy
Slide 51: IONSYS potential to reduce hospital costs
52 Disruptive innovation IONSYS™ potential to reduce hospital costs Harmful IV PCA medication errors cost $6,9432,7 per event Harmful IVPCA device errors cost $7,2812,7 per event IONSYS™ potential to reduce AEs, pump and programming errors, and pain management related nursing activities. IONSYS™ 1,2
Slide 52: Manufacturing systems and commercial scale production
53 Disruptive innovation Manufacturing systems and commercial scale production established Lakewood, NJ facility Capacity for 2M units per year at launch Expansion equipment available for more than 15M units per year More than $40M invested capital by Alza/ Johnson & Johnson prior to our acquisition
Slide 53: The value of balanced analgesia
54 Disruptive innovation The value of balanced analgesia Post op Analgesic (dose) Opioid use NSAID Placebo 56.5 mg Ketorolac (30 mg) 37.8 mg COX–2 Inhibitor Placebo 19.7 mg Celecoxib (200mg) 15.1 mg NMDA antagonist Placebo 72.1 mg Ketamine (10 mcg/kg/min) 50.5 mg Alpha-2 adrenergic agonists Placebo
Slide 54: US in-hospital post-operative pain market
55 Patient population United States in-hospital post-operative pain (IPOP) market In-hospital surgical procedures, 2011 Days of use average, 2012 22,186,6341 1.74 days2 Patients Proportion IPOP receiving IV PCA2 1,373,423 6.2% IPOP receiving IV opioids not IV PCA2 7,073,597 31.9% IPOP not receiving
Slide 55: Europe and Asia post-operative pain market
56 Patient population Europe and Asia in-hospital post-operative pain market The majority of in-hospital post-operative pain patients receive IV opioids Estimated total surgical procedures Estimated days of use average 80,231,843 2.24 days In-hospital post-op pain treatment Patients Proportion IPOP
Slide 56: Regulatory submissions complete and reviews underway
57 United States FDA sNDA • Submitted 30 June 2014 • Accepted for filing 11 Sept 2014 • PDUFA action date 30 April 2015 European CHMP MAA • Submitted 3 Sept 2014 • Accepted for filing 24 Sept 2014 • Preliminary opinion anticipated 22 January 2015 Disruptive innovation Regulatory submissions complete
Slide 57: News flow
58 Publications 2 publications submitted to date, with 4 additional scheduled for submission in 2014 Clinical trial Pediatric study expected to begin Q1 2015 Early cycle reviews EMA January 2015 PDUFA April 2015 Disruptive innovation News flow I Growth drivers today What hospitals want Launching 2 n
Slide 58: Potential future of post-operative pain management
59 Disruptive innovation The potential future of post-operative pain management IONSYS™ is currently not approved for commercial use in any market. I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostasis
Slide 59: Hemostasis in surgery: RECOTHROM, RAPLIXA, PREVELEAK
Changing the management of hemostasis in surgery: RECOTHROM®, RAPLIXA™ and PREVELEAK™ Jason Campagna The Medicines Company
Slide 60: Hemostasis portfolio market
61 Hemostasis portfolio 110 million surgical procedures/year worldwide result in bleeding that requires hemostatic product $192M $208M $5M $86M $174M US market $665 million Liquid Fibrin Sealants Flowables Pads Glues Thrombins $173M $99M $188M $20M EU market $480 million Liquid Fibrin Sealants Flowa
Slide 61: Competitive landscape for hemostasis
62 Tissue bleeding Data on file. The Medicines Company. Simple Skin Graft surface Tissue flaps Organ injuries Complex Bone Complex organ injuries Avulsion wounds Vascular anastomotic bleeding Moderate Mild Low pressure High pressure Powdered “Actives” Flowables Mechanical Hemostats Patches Synthetic
Slide 62: Complementary products for surgeons
63 Hemostasis portfolio Complementary products for surgeons RECOTHROM® Thrombin Topical (recombinant) PREVELEAK™ RAPLIXA™ (sealant powder) Status US market US and EU market BLA/MAA review Classification Aqueous recombinant thrombin hemostat Surgical sealant Powdered fibrinogen/ thrombin hemostat Ind
Slide 63: PCI patients: Cangrelor and ANGIOMAX
PCI patients: Cangrelor and ANGIOMAX® Makis Deliargyris The Medicines Company
Slide 64: The job to be done in PCI: arterial thrombosis
65 The job to be done in PCI Manage acute arterial thrombosis Stalker TJ. Blood. 2013;121:1875-1885. Mouse cremaster muscle arteriole Laser injury +2.1 seconds Laser injury +5 minutes, 3D reconstruction, Isosurface view Platelet labeling, 15 µm Albumin Non-activated platelets: CD41 Activated platele
Slide 65: Acute thrombin and platelet inhibition is desirable
66 The job to be done in PCI Acute thrombin and platelet inhibition is desirable Control Stalker TJ. Blood 2013;121:1875-1885 Direct thrombin inhibitor P2Y12 inhibitor Fibrin Non-activated platelets: CD41 Activated platelets: P-selectin I Growth drivers today What hospitals want Launching 2 new anti
Slide 66: Alleviate acute thrombotic risk in first 24 hours
67 Acute myocardial infarction (STEMI) Cardiac death/repeat infarction/stent thrombosis The job to be done in PCI Alleviate acute thrombotic risk during the first 24 hours 0 1 2 3 4 5 6 7 0 20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 Percent (%) Days HORIZONS-AMI (n=3,602) 0
Slide 67: Move patient through care pathway quickly
68 The job to be done in PCI Move patient through care pathway quickly and efficiently FRISC1 (Lancet 1999) 4 days RITA-33 (Lancet 2002) 3 days CRUSADE44 (Circulation 2005) 23 hours ACUITY5 (NEJM 2006) 20 hours CHAMPION7 PHOENIX (NEJM 2013) 4 hours CHAMPION6 PLATFORM (NEJM 2009) 8 hours PCI-CURE2 (L
Slide 68: Make sure drugs reach site of action
69 The job to be done in PCI Make sure drugs have reached the intended site of action I Growth drivers today What hospitals want Launching 2 new antibiotics Changing the management of pain in hospital Changing the management of hemostasis in surgery PCI patients ANGIOMAX® IP II Growth drivers ahead
Slide 69: Rapid onset and offset of platelet inhibition
70 Allows rapid onset and offset of platelet inhibition 800 700 600 500 400 300 200 160 140 120 100 80 60 40 20 0 0 Time (minutes) Bolus 30µg/kg Infusion 4µg/kg/min Recovery time 60 minutes Concentration (ng/mL) % Platelet aggregation (impedance) Plasma concentration (Cangrelor) Platelet activity Ak
Slide 70: Cangrelor clinical results: efficacy
71 Cangrelor Clinical trials results in PCI — Efficacy Adapted from Steg PG, et al. Lancet 2013; 382:1891-92. Patient-level pooled Phase 3 clinical trial data (N=24,910) Ischemic outcomes at 48 hours Odds ratio cangrelor:clopidogrel events (95% CI) Death, MI, IDR, ST Death, QMI, IDR, ST Death, MI, I
Slide 71: Cangrelor clinical results: safety
72 Cangrelor Clinical trials results in PCI — Safety Patient-level pooled Phase 3 clinical trial data (N=24,910) Non-CABG bleeding at 48 hours Bleeding Scale Cangrelor (n=12,565) Clopidogrel (n=12,542) Odds Ratio (95% CI) P-value GUSTO Severe 28 (0.2%) 23 (0.2%) 1.22 (0.70, 2.11) 0.49 GUSTO Moderate
Slide 72: Cangrelor active regulatory review
73 Cangrelor Active, ongoing regulatory review United States (FDA)—NDA Status Europe (EMA)—MAA Status Complete Response Letter received on April 30, 2014 Resubmission planned before year-end Anticipated • Advisory Committee Meeting • Six-month review Day 180 List of Outstanding Issues (LOI) – Septem
Slide 73: ANGIOMAX clinical trial data platform
74 ANGIOMAX® (bivalirudin)/ANGIOX® Extensive clinical trial data platform with more planned in 2015-16 Study Year Size Comparator Patients REPLACE-21 2003 6,002 UFH + GPI PCI – Elective ACUITY2 2006 13,819 UFH + GPI PCI - NSTEMI ISAR-REACT 33 2008 4,570 UFH PCI - Elective HORIZONS-AMI4 2008 3,602 UF
Slide 74: Real-world data underscore market leadership
75 ANGIOMAX®/ANGIOX® Real-world data in US underscore market leadership position in PCI 452,044 PCI patients 2004–2008 Odds Ratio In-Hospital Death versus UFH + GPI (95% CI) P-value Bivalirudin alone 0.75 (0.68–0.83) <0.0001 Bivalirudin + GPI 0.89 (0.78–1.01) 0.08 Heparin alone 1.09 (1.01–1.18) 0.04
Slide 75: ANGIOMAX growth driven by US sales
76 ANGIOMAX®/ANGIOX® Growth driven by US sales has continued in 2014 # of Publications 3 8 10 21 20 30 26 24 40 47 48 35 36 # of Accounts Purchasing 216 597 939 1,133 1,285 1,411 1,618 1,664 1,727 1,777 1,875 1,916 1,939 # of Accts Purchasing $.5M or more 0 5 15 38 59 85 108 177 225 282 300 343 400
Slide 76: Investments in potential new indications
77 Leon MB et al. NEJM. 2010; 363:1597-1607. ANGIOMAX®/ANGIOX® Investments in potential new indications continue Outcome TAVR (N=179) No. of pts (%) Control (N=179) No. of pts (%) P-value Vascular complications 55 (30.7) 9 (5.0) <0.001 Major vascular complications 29 (16.2) 2 (1.1) <0.001 Major blee
Slide 77: BRAVO and ENDOMAX trials
78 ANGIOMAX®/ANGIOX® Investments in potential new indications continue BRAVO 2–3 Trial (n=800) Open Label ANGIOMAX® vs. heparin in TAVR ENDOMAX Trial (n=4000) Double Blind ANGIOMAX® vs. heparin in carotid stenting + peripheral interventions including critical limb ischemia 6 EU countries + Canada—35
Slide 78: Leadership in cardiac catheterization laboratories
79 Leadership in cardiac catheterization laboratories In the United States we also promote products for our partners, AstraZeneca and Boston Scientific BRILINTA® (ticagrelor) PROMUS PREMIER™ Stent System Ticagrelor tablets Indicated for ACS Everolimus-Eluting Platinum Chromium Coronary Stent System
Slide 79: In Summary
80 • Contemporary management of acute cardiac patients undergoing PCI requires fast and effective therapies • Cangrelor and ANGIOMAX® are both ideal for the PCI setting • Cangrelor is under active regulatory review in the US and Europe • Assuming exclusivity, ANGIOMAX® will continue to grow – New In
Slide 80: ANGIOMAX IP
ANGIOMAX® IP Ed Haug Frommer Lawrence & Haug, LLP
Slide 81: ANGIOMAX litigations settled or tried
82 ANGIOMAX® litigations Settled or tried Teva Settled ’727 and ’343 patents valid – infringed APP Settled ’727 and ’343 patents valid – infringed Hospira On appeal ’727 and ’343 patents valid – not infringed Mylan District court decision ’727 valid and enforceable – infringed • Awaiting entry of pe
Slide 82: ANGIOMAX litigations pending
83 ANGIOMAX® litigations Pending New Jersey cases Sun Stayed DRL No trial date Apotex Trial scheduled for August 2015 Aurobindo No schedule yet Pending North Carolina cases Excela Schedule to Markman June 2015, no trial date Accord/Intas No schedule yet I Growth drivers today What hospitals want Lau
Slide 83: ANGIOMAX patents/regulatory timeline
84 2015 2016 2019 2020 2029 ANGIOMAX® patents/regulatory timeline June 15, 2015 ‘404 patent exp. w/ ped exclusivity Sept. 2015 Apotex’s 30 month stay expires Sept. 2016 Aurobindo’s 30 month stay expires Dec. 2016 Accord/Intas’ 30 month stay expires June 30, 2019 Teva anticipated launch date Sept. 20
Slide 84: Questions, answers and summary
Questions, answers and summary Clive Meanwell
Slide 85: Growth drivers today summary
86 We are moving forward aggressively with our hospital portfolio Our hemostasis portfolio is making progress ORBACTIV™ and MINOCIN® IV launches are underway in US IONSYS™ is under regulatory review with potential US launch in mid-2015 Cangrelor is under active regulatory review in both US and Europ
Slide 86: Break
BREAK
Slide 87: Growth drivers ahead
Growth drivers ahead Scott Johnson The Medicines Company
Slide 88: What atherosclerosis needs
What atherosclerosis needs Greg Schwartz University of Colorado disclosures: research grants to institution — roche, sanofi,anthera,reserverlogix
Slide 89: Emerging strategies for treatment of dyslipidemia
Emerging strategies for treatment of dyslipidemia • Gregory G Schwartz, MD PhD • University of Colorado, Denver • 5 Nov 2014 Disclosures: Research grants to institution — Roche, Sanofi, Anthera, Resverlogix A cardiologist’s perspective
Slide 90: No drug added to statin shown to provide incremental benefit
To date, no drug added to statin has been shown to provide incremental clinical benefit 1987 – 2014: 27 years since first statin approved
Slide 91: Residual cardiovascular risk in statin trials
Residual cardiovascular risk in selected statin trials To what extent is residual risk attributable to lipoprotein abnormalities and modifiable by lipoprotein interventions? 100 80 60 40 20 0 Residual Events Prevented Events 4S LIPID CARE HPS WOS AF/5ex JUPITER 2° Prevention High Risk 1° Prevention
Slide 92: Major classes of lipoproteins and targeted approaches
3 major classes of lipoproteins and targeted approaches to their modification Lipoprotein class Biological function LDL Deliver cholesterol to cells HDL Remove excess cholesterol from tissue sites and bring to liver for excretion in bile Triglyceride-rich lipoproteins Deliver fatty acids to cells fo
Slide 93: LDL: still the best target?
LDL – still the best target? • Is residual CV risk related to LDL-C in patients treated with statins? • How can we further lower LDL-C? • What kind of clinical benefit can we expect? Cholesterol ester Apoprotein B-100 Phospholipid Unesterified cholesterol LDL
Slide 94: LDL-C and residual CV risk with statins
Relation of LDL-C to residual CV risk among 38,153 patients treated with statins 0.0 0.2 0.4 0.6 0.8 1.0 1.2 <50 50-<75 75-<100 100-<125 125-<150 150-<175 =175 Relative risk Range of LDL-C on statin treatment Boekholdt M., et al. J Am Coll Cardiol 2014;64:485-94 P for trend <0.001
Slide 95: LDL-C reduction beyond statins
LDL-C reduction beyond statins: Existing and emerging approaches -15 -25 -30 -40 -40 -50 -70 -80 -70 -60 -50 -40 -30 -20 -10 0 % LDL-C reduction (from statin baseline)
Slide 96: Effect of PCSK9 monoclonal antibody on LDL-C
Roth EM et al. N Engl J Med 2012;367:1891-1900. Effect of PCSK9 monoclonal antibody on LDL-C LDL Cholesterol (mean percent change from baseline) Atorvastatin, 80 mg, plus placebo Atorvastatin, 10 mg, plus SAR236553 Atorvastatin, 80 mg, plus SAR236553 Baseline (all on atorva 10mg) Week
Slide 97: Predicted contrast in CV risk by PCSK9 inhibition
Predicted contrast in CV risk by inhibition of PCSK9 Relative risk Range of LDL-C on statin treatment Boekholdt M., et al. J Am Coll Cardiol 2014;64:485-94 HR 0.79 Placebo PCSK9 inhibition
Slide 98: HDL structure
HDL ApoA1 Apo E Cholesterol Ester ApoA-II Triglyceride Apo C ApoA1 Unesterified Cholesterol Apo C Phospholipid
Slide 99: HDL and ApoA-I as target: key questions
HDL and ApoA-I as target of therapy: Key questions 1. Are plasma concentrations of HDL-C and ApoA-I related to risk in patients treated with statins? 2. Is HDL functional in patients with atherosclerosis? 3. Which approaches are promising for HDL-based treatment?
Slide 100: ApoA1 and CV risk in statin-treated patients
ApoA1 and CV risk in statin-treated patients *4S, AFCAPS, LIPID, CARDS, TNT, IDEAL, SPARCL, JUPITER; multivariable adjustment Boekholdt et al., Circulation 2013; 128:1504-12 Hazard ratio for MCVE Apolipoprotein A-1 <122 mg/dL Apolipoprotein A-1 122-137 mg/dL Apolipoprotein A-1 137-150 mg/dL Apolipop
Slide 101: HDL-C raising trials that did not reduce CV risk
Completed CV outcome trials with agents that increase HDL-C concentration, but did not reduce CV risk • Niacin ~15% increase in HDL-C • CETP inhibitors (dalcetrapib, torcetrapib) ~30-70% increase in HDL-C
Slide 102: Why did niacin and CETPi trials fail?
Why did niacin and CETPi trials fail? • Undesirable effects of the drugs: – Niacin: impaired glucose tolerance, serious GI events, infections – CETPi: increased blood pressure, C-reactive protein • HDL function was abnormal
Slide 103: Concentration versus function
Concentration Function CETP Inhibition with dalcetrapib No association between baseline HDL-C (by quintiles) and risk of primary endpoint n=15,872 patients with ACS Schwartz et al N Engl J Med. 2012;367:2089-99
Slide 104: HDL cholesterol efflux capacity reduced in CAD
In vitro cholesterol efflux capacity of HDL is reduced in patients with CAD Patel P J et al. Eur J Heart Fail 2013;15:1215-19 No CAD (n=46) HDL efflux capacity (normalized to samples from healthy volunteers) CAD (n=23) p=0.02
Slide 105: ApoA1 Milano mutation
ApoA1 Milano: A mutation associated with increased HDL function • Low HDL-C and A1 concentration, increased triglycerides • Longevity without cardiovascular disease • High cholesterol efflux capacity of HDL in vitro, anti-inflammatory effects Franceschini et al., Metabolism 1981;30:502 Favari et al.
Slide 106: Summary
Summary PCSK9 • Key regulator of LDL-C levels • Abrogating its function reduces LDL-C and may reduce CV risk HDL and ApoA-I • HDL-C concentration is easy to measure, but HDL function may be more important. • To date, 2 strategies that increase HDL-C have not reduced CV risk (niacin, CETP inhibitors)
Slide 107: Atherosclerosis: ApoA1-Milano and PCSK9sc
Changing the management of atherosclerosis: ApoA1-Milano and PCSK9sc David Kallend The Medicines Company Changing the management of atherosclerosis: ApoA1-Milano and PCSK9sc David Kallend The Medicines Company
Slide 108: High density lipoprotein
109 High density lipoprotein Cholesterol transport particles HDL is the smallest of the lipoproteins with various sub-types1 HDL plays a key role in reverse cholesterol transport2 Prebeta-1 HDL removes cholesterol from atherosclerotic plaque3,4,5,6 Larger HDL particles transport cholesterol to the l
Slide 109: Apolipoprotein A1
110 ApoA1 plays a key role in HDL remodeling and interacts with ABCA1 which mediates cholesterol efflux1 Loss of function leads to increased risk of CV disease1 Gain of function leads to decreased risk of CV disease and atherosclerosis2 ApoA1-Milano induces plaque regression in rabbits3 CV disease i
Slide 110: ABCA1 cholesterol efflux regulatory protein
111 ABCA1 Cholesterol efflux regulatory protein ABCA1 is the “pump” which mediates the efflux of cholesterol to lipid poor ApoA1 forming mature HDL particles1 ABCA1 plays a key role in reverse cholesterol transport2 Loss of function is seen in Tangier Disease3 which is associated with premature athe
Slide 111: HDL efflux rates more critical than HDL-C levels
112 High density lipoprotein HDL efflux rates are potentially more critical than HDL-C levels Cholesterol efflux capacity has been shown to have an indirect association with the presence of coronary artery disease1 Prebeta 1 HDL levels correlate strongly with ABCA1 mediated cholesterol efflux2 These
Slide 112: MDCO-216 Phase I trial completed
113 Up to 4 fold increase in ABCA1 efflux compared with baseline ABCA1 efflux was maximally increased by 20 mg/kg in CAD patients The ApoA1-Milano lipid phenotype of low HDL-C and raised TG was observed MDCO-216 was well tolerated at all doses Full data planned to be presented at AHA MDCO-216 (ApoA1
Slide 113: HDL function with MDCO-216, dalcetrapib and niacin
114 0 2 4 6 8 10 12 14 16 18 20 Baseline Post Baseline dalcetrapib (dal-ACUTE) placebo adjusted MDCO-216 20 mg/kg niacin (HIFUN) MDCO-216 HDL function with MDCO-216, dalcetrapib and niacin 14 fold greater increases in ABCA1 efflux with MDCO-216 in CAD patients compared to dalcetrapib1 8 fold increas
Slide 114: MDCO-216 clinical proof of concept established
115 MDCO-216 Clinical proof of concept established previously I Growth drivers today II Growth drivers ahead What atherosclerosis needs Changing the management of atherosclerosis What multidrug resistance needs Managing CRE Changing anesthesia III Business strategy IV What’s next Placebo (N=11) MDCO
Slide 115: Phase 2 MILANO-DRIVE study
116 Phase 2 trial ApoA1-Milano, MILANO-DRIVE Phase 2 dose finding study expected to begin in 2015 Study to be designed to reconfirm previous findings of atherosclerosis regression on intravascular ultrasound (IVUS) Dose for Phase 3 will be selected on: • Coronary imaging • Cholesterol efflux • Pharm
Slide 116: MDCO-216 development plan
117 Phase 2 MILANO-DRIVE study: Dose and regimen will be selected for Phase 3 Anticipated Phase 3 study • Cardiovascular mortality and morbidity study in 6,000–8,000 ACS patients • Primary endpoint major acute coronary events (CV death, non-fatal MI and stroke) Manufacturing scale-up steps Global pa
Slide 117: ALN-PCSsc PCSK9 synthesis inhibitor
ALN-PCSsc First in Class PCSK9 Synthesis Inhibitor
Slide 118: ALN-PCSsc IV formulation study results
119 Rapid, dose-dependent, and durable knockdown of PCSK9 of up to 84% with mean lowering of 68% at 0.4 mg/kg group Significant reductions in LDL-C of up to 50% with mean lowering of 41% at 0.4 mg/kg group Single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers. P
Slide 119: ALN-PCSsc pre-clinical efficacy in NHP
120 Up to 96% PCSK9 knockdown Up to 77% LDL-C lowering (in absence of statins) Supports once-monthly or possibly once-quarterly dosing ALN-PCSsc pre-clinical efficacy in NHP: Single dose data Potent durable PCSK9 knockdown and LDL-C lowering I Growth drivers today II Growth drivers ahead What athero
Slide 120: Potential profile of PCSK9 synthesis inhibitor
121 Clamped PCSK9 knockdown and LDL-C lowering Monthly or, possibly, quarterly SC dosing LDL-C lowering independent of baseline PCSK9 levels Low SC injection volumes <1 mL Potential synergy with statins ALN-PCSsc PCSK9 synthesis inhibitor Potential profile of PCSK9 synthesis inhibitor I Growth drive
Slide 121: Anticipated subcutaneous Phase 1 study design
122 Study design for single ascending dose phase Study design for multiple dose phase Patient Population Healthy subjects (single dose) Healthy subjects and patients on statins (multiple dose) Study Size Up to 28 subjects single dose Up to 48 subjects multiple doses ALN-PCSsc Anticipated subcutaneou
Slide 122: Phase 1 endpoints and status
123 Endpoints Safety LDL-C and PCSK9 reduction PK, other lipids and lipoproteins Status CTA filed October 2014 Initial results mid-2015 ALN-PCSsc Anticipated sub-cutaneous Phase 1 placebo controlled dosing study in humans I Growth drivers today II Growth drivers ahead What atherosclerosis needs Chan
Slide 123: Current regulatory strategy
124 We believe in this fast route to filing of ALN-PCSsc Complete Phase 1 SAD / MD study expected Q2 2015 Perform multi-dose Phase 2 study to confirm dose and dosing regimen for Phase 3 Proceed to pivotal Phase 3 studies • Lipid lowering studies • Long term studies for safety • CV mortality and morb
Slide 124: ALN-PCSsc partnerships
125 ALN-PCSsc Partnerships Collaboration between The Medicines Company and Alnylam Pharmaceuticals, Inc. to advance ALN-PCSsc program Create industry-leading effort for best-in-class medicine for PCSK9 antagonism • $25M upfront payment • Up to $180M Milestone payments • Scaled double-digit royalties
Slide 125: Anticipated news flow
126 MDCO-216 Presentation of Phase 1 SAD data at AHA November 2014 Publication of manuscript of Phase 1 SAD study Q1 2015 (estimated) Announcement of FPI Phase 2 study Q2 2015 First results Q2 2016 Manufacturing milestones MDCO-216 and ALN-PCSsc Anticipated news flow I Growth drivers today II Growth
Slide 126: Backup: What multidrug resistance needs
Backup What multidrug resistance needs Ron Jones JMI Laboratories What multidrug resistance needs Ron Jones JMI Laboratories
Slide 127: What multidrug resistance needs
What multidrug resistance needs Ron Jones JMI Laboratories
Slide 128: Antimicrobial resistance
Antimicrobial resistance • Resistance among Gram-negative bacilli is escalating due to mobile genes encoding potent drug inactivating enzymes (e.g., ß-lactamases) • Epidemiology is linked worldwide via patient/leisure travel and military conflicts/population migrations • Solutions are intuitive, but
Slide 129: Beta-lactamase inhibitors
Beta-lactamase inhibitors (BLI) Bind in the active site of beta-lactamase Inactivate the enzyme Prevent degradation of the antibiotic Antibiotic Penicillin Cephalosporin Carbapenem e.g., TEM-1 Inactive Beta-Lactamase Inhibitor e.g., ESBL e.g., KPC-2 RPX-7009 bound in ESBL CTX-M-15 Bacterial beta-lac
Slide 130: Resistant Klebsiella outbreaks in New York: the KPC story
Timeframe 2000–2006 • 602 Klebsiella isolates from 11 hospitalsa • 45% ESBL positive • 3.3% of these were KPC positive (from 7 hospitals) – Highly resistant to cephalosporins and carbapenems • KPC-2 and -3: plasmid encoded serine ß-lactamasesb – Efficiently hydrolyze carbapenems (Class A enzyme) – R
Slide 131: Mortality and morbidity of KPC infections
Mortality Attributable mortality of KPC producing Klebsiella blood stream infections—48% vs. 12% for non-KPC producing Klebsiella blood stream infections Morbidity Patients with KPC-producing Klebsiella blood stream infections significantly more likely than similar patients without bacteremia to req
Slide 132: ESBLs and carbapenemases spreading worldwide
Similar trends are emerging in the US and worldwide ESBLs and Carbapenemases in Enterobacteriaceae: Similar trends Carbapenem-resistant Enterobacteriaceae reported in 47 States (US CDC, February 2014) 40% 30% 20% 10% 0% 1980s 1990s 2000s 50% Incidence Beta-lactamase mediated resistance can dissemina
Slide 133: Six year trend of ESBL and CRE
Six year trend of ESBL and CRE in the 2007–2012 SENTRY Programa United States Organism (no. tested) Resistanceb % by Year 2007 2008 2009 2010 2011 2012 E. coli (9,743) ESBL 5.6 6.0 9.5 10.0 12.8 11.6 CRE 0.1 0.0 0.1 0.1 0.4 0.3 Klebsiella spp. (7,677) ESBL 15.4 13.2 12.7 12.5 14.6 14.1 CRE 5.5 4.8 5
Slide 134: Worldwide spread of carbapenemases
Worldwide Spread of Carbapenemases Lancet ID 2013;13:785, Page 2
Slide 135: Emerging resistances among E. coli and Klebsiella
Summary of emerging resistances among E. coli and Klebsiella spp. (SENTRY Program, 2011) Regional variations % by area (trend)a Organism (no. tested) Resistanceb USA China Europe LATAMb E. coli (5,118) ESBL 12.8 (+) 73.8 (+) 19.4 (+) 37.1 (+) CRE 0.4 (+) 2.1 (+) 0.1 (NC) 0.0 (NC) Klebsiella spp (3,2
Slide 136: CDC considers CRE an urgent threat
Resistance is highly transmittable (plasmids) Difficult infection control challenges (e.g., NIH Clinical Center outbreak) Lack of adoption of new definitions in microbiology laboratories may cause hospitals to “miss” resistance Potential for community spread • E. coli is a common cause of community
Slide 137: Managing CRE: CARBAVANCE and beta-lactamase inhibitors
Managing CRE: CARBAVANCE™ and beta-lactamase inhibitors Mike Dudley The Medicines Company
Slide 138: Options for treatment of CRE infections
139 Gram-negative multidrug resistance (MDR) Options for treatment of infections due to carbapenem-resistant Enterobacteriaceae (CRE) Class Tetracyclines (tigecycline) Polymyxins (colistin) Aminoglycosides Beta-lactams Daikos et. al., J Antmicrob Chemother. 2014;58:2322-8. I Growth drivers today II
Slide 139: New beta-lactamase inhibitor combinations in development
140 Gram-negative MDR New beta-lactamase inhibitor combinations in clinical development Beta-lactam antibiotic Inhibitor Examples Previously Approved “New” Ceftazidime + avibactam Imipenem/cilastatin + MK7655 Meropenem + RPX-7009 (CARBAVANCE™) New “Old” Ceftolozane + tazobactam Key serine beta-lacta
Slide 140: Why a carbapenem for a BLI combination?
141 Bloodstream isolates of carbapenemase-negative, ESBL-producing Enterobacteriaceae from US Hospitals Gram-negative MDR Why a carbapenem for a BLI combination? Data are MIC90 Meropenem Imipenem Ertapenem Ceftazidime Pip/Tazo Aztreo All strains, ESBL Phenotype (151) 0.12 0.5 0.5 >8 >64 >8 Escherich
Slide 141: Discovery of RPX-7009
142 Gram-negative MDR Discovery of RPX-7009—new class of beta-lactamase inhibitors1 Series of cyclic boronic acid compounds synthesized Potent inhibitory activity against Class A and C serine beta-lactamases Optimized for: • Inhibition of serine carbapenemases • Pharmacology with carbapenems In Vitr
Slide 142: In vitro activity of meropenem with RPX-7009
143 Gram-negative MDR In vitro activity of meropenem alone or with RPX-7009 against Enterobacteriaceae1 Organism (no. tested) Antimicrobial agent* MIC 50% 90% Enterobacteriaceae (n=200) Meropenem 0.12 32 Mer+RPX-7009 8 (µg/mL) 0.03 0.5 K. pneumoniae (n=76) Meropenem 16 >32 Mer+RPX-7009 8 (µg/mL) 0.0
Slide 143: CARBAVANCE versus cephalosporin-based combinations
144 0% 20% 40% 60% 80% 100% <=0.06 0.125 0.25 0.5 1 2 4 8 16 32 Cumulative % of strains inhibited MIC of beta-lactam antibiotic Gram-negative MDR In vitro comparison of CARBAVANCE™ (Meropenem + RPX-7009) vs. cephalosporin-based combinations N=235 MIC50 MIC90 Meropenem Alone + RPX-7009 (4 µg/mL) 0.12
Slide 144: Pharmacokinetics of CARBAVANCE in human subjects
145 0.1 1.0 10.0 100.0 0 2 4 6 8 10 12 Meropenem 2g Alone Meropenem 2g + RPX7009 2000 mg Time (h) Meropenem concentration (mg/L) 0.1 1.0 10.0 100.0 0 2 4 6 8 10 12 RPX-7009 concentration (mg/L) Time (h) RPX7009 2000 mg Alone RPX7009 2000 mg + Meropenem 2g Gram-negative MDR Pharmacokinetics of CARBAV
Slide 145: Pharmacodynamics in hollow fiber model
146 Gram-negative MDR Pharmacodynamics of simulated human dosage regimens of meropenem + RPX-7009 against KPC-producing CRE in an in vitro hollow fiber model Strain Beta-Lactamases Meropenem MIC (mg/L) Change in Log CFU over 24 hours Alone + RPX-7009 8ug/mL E. coli EC1007 KPC-3 16 =0.06 >4 E. cloaca
Slide 146: CARBAVANCE pivotal trial program design
147 Gram-negative MDR CARBAVANCE™ pivotal clinical trial program design TANGO I TANGO II Patients Complicated UTI and AP CRE suspected cUTI, HABP, VABP and/or bacteremia Design Randomized 1:1 Double blind Randomized 2:1 Open label Comparator Piperacillin/Tazobactam Best available therapy Total patie
Slide 147: What's next? CRE in other settings
148 Gram-negative MDR What’s next? CRE is in other settings – potential implications for MDCO’s oral BLI combination Initial wave of CRE cases mostly in larger metropolitan hospitals Long-term acute care hospitals in Chicago1 • Median duration of colonization 16 months • High risk of transmission Co
Slide 148: Broad-spectrum carbapenemase inhibitors
149 Gram-negative MDR Broad-spectrum carbapenemase inhibitors (BCI) restore the potency of beta-lactam antibiotics versus major carbapenems, including NDM-1 45 KPC; 7 OXA-48 type; 36 VIM; 28 NDM-1; 18 IMP. All inhibitors tested at a fixed 4 µg/mL. 367 MDR isolates enriched for carbapenemase producti
Slide 149: Gram-negative MDR news flow
150 Gram-negative MDR News flow TANGO Phase 3 protocols reviewed with FDA and EMA 1Q 2014 BARDA contract awarded 2Q 2014 Phase 3 trial set up 3Q 2014 TANGO first patient enrolled 4Q 2014 BARDA award of next option periods in CARBAVANCE™ contract 4Q 2015 Anticipate clinical candidate for next generat
Slide 150: Changing anesthesia: ABP-700
Changing anesthesia: ABP-700 Jason Campanga The Medicines Company
Slide 151: The beginning of the era of anesthesia
152 The beginning of the era of anesthesia. Innovations in anesthesia 1846 1846 Massachusetts General Hospital surgeon John Collins Warren removed a tumor from the neck of Edward Abbott under ether anesthesia. I Growth drivers today II Growth drivers ahead What atherosclerosis needs Changing the man
Slide 152: The first barbiturates
153 The first barbiturates. Diethyl-barbituric acid, also known as barbital, malonal, or gardenal, was first introduced clinically as a hypnotic by the German companies Merck and Bayer and Co in 1904. Innovations in anesthesia 1904 1904 López-Muñoz et al 2005. I Growth drivers today II Growth driver
Slide 153: The first intravenous anesthesia
154 The first intravenous anesthesia. Sodium thiopental (Pentothal™) first used in human beings on March 8, 1934, by Dr. Ralph M. Waters in Wisconsin. The drug subsequently revolutionized anesthesia by providing an intravenous route to induce general anesthesia. Sodium thiopental is still a core med
Slide 154: Great age of inhaled anesthetic development
155 The great age of inhaled anesthetic development. Ether-derived Methoxyflurane (60s) Desflurane (70s)* Enflurane (60s) Isoflurane (70s) Sevoflurane (70s)** Innovations in anesthesia 1940s – 1970s 1940s–1970s *Desflurane marketed in 1993 . **Sevoflurane marketed in 1995. Chloroform-derived Halotha
Slide 155: Search for barbiturate replacements
156 Intensive search for barbiturate replacements. 1971–73 althesin 1972 etomidate 1973 propofol original formulation Innovations in anesthesia 1960s – 1970s 1960s–1970s I Growth drivers today II Growth drivers ahead What atherosclerosis needs Changing the management of atherosclerosis What multidru
Slide 156: Innovations in anesthesia 1980s–1990s
157 Innovations in anesthesia 1980s–1990s 1980s–1990s I Growth drivers today II Growth drivers ahead What atherosclerosis needs Changing the management of atherosclerosis What multidrug resistance needs Managing CRE Changing anesthesia III Business strategy IV What’s next Pace of innovation accelera
Slide 157: Growth of outpatient surgery
158 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 Surgeries by Setting, 1981–2006 Inpatient Surgeries Outpatient Surgeries Laryngeal Mask Airway (LMA) Etomidate Propofol Cu
Slide 158: Measuring sedation and anesthesia
159 It’s more complicated than “awake” or “asleep” Measuring “sedation” and “anesthesia” CONTINUUM AND LEVELS OF SEDATION Minimum sedation/ anxiolysis Moderate/ sedation analgesia (previously conscious sedation) “MAC” Deep sedation/ analgesia General anesthesia I Growth drivers today II Growth drive
Slide 159: Widespread use of propofol exposed the risks
160 Anesthesia provider professional societies (American Society of Anesthesiologists, American Association of Nurse Anesthetists) Government hospital accreditation bodies (Center for Medicare Services, Joint Commission) Regulatory Agencies responsible for drug approval and safety (FDA) Published Li
Slide 160: FDA rejects petition to remove warning from label
161 FDA rejects petition to remove warning from label Excerpt from FDA letter U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Janet Woodcock, M.D. to Richard M. Cooper, Esq, Docket No. FDA-2005-P-0059, August 11, 2010. I Growth drivers today II Growth drivers ahead What a
Slide 161: FDA rejects petition to remove warning from label
162 FDA rejects petition to remove warning from label Excerpt from FDA letter U.S. Food and Drug Administration, Center for Drug Evaluation and Research, Janet Woodcock, M.D. to Richard M. Cooper, Esq, Docket No. FDA-2005-P-0059, August 11, 2010. I Growth drivers today II Growth drivers ahead What a
Slide 162: Overall safety of anesthesia is high
163 Anesthesia-related deaths have decreased over the last 25 years from two per 10,000 anesthetics administered to one per 200,000 to 300,000.1 The American Society of Anesthesiologists says a person is more likely to be struck by lightning than die from anesthesia-related complications.2 This is l
Slide 163: Addressing the global surgery crisis
164 Addressing the global surgery crisis Taking a more universal view MORE RESOURCES vs. BETTER TOOLS I Growth drivers today II Growth drivers ahead What atherosclerosis needs Changing the management of atherosclerosis What multidrug resistance needs Managing CRE Changing anesthesia III Business str
Slide 164: ABP-700 improved anesthetic by design
165 ABP-700 An improved anesthetic by design ABP-700 Selected from diverse, highly “tunable” compound library Ester chemistry of “soft analogues” I Growth drivers today II Growth drivers ahead What atherosclerosis needs Changing the management of atherosclerosis What multidrug resistance needs Manag
Slide 165: ABP-700 preclinical study in dogs: onset and offset
166 ABP-700 preclinical study in dogs Achieves rapid onset and offset of anesthesia Campagna J, et al. Advancing Novel Anesthetics: Pharmacodynamic and Pharmacokinetic Studies of Cyclopropyl-methoxycarbonyl Metomidate in Dogs. Anesthesiology. 2014. Burst Suppression Ratio Time (min) 0 50 100 150 200
Slide 166: ABP-700 recovery times constant and short
167 ABP-700 preclinical study in dogs Recovery times constant and short, independent of dose Dogs emerge from anesthesia and recover normal function faster with ABP-700 when compared to propofol or etomidate Time to recovery is independent of duration of anesthesia Comparison of recovery from 120-mi
Slide 167: Preliminary results: human experience mirrors animal data
168 Preliminary results Human experience mirrors animal data including dog data shown here ABP-700 is a rapidly acting IV anesthetic Appears to have a highly titratable PD effect Safety profile is consistent with pre-clinical animal data After bolus injection, rapidly reversible anesthetic effect wi
Slide 168: Upcoming milestones
169 Upcoming milestones Expect Phase 1 program completion by end of 2014 Press release on Phase 1 program in January at JPMorgan Healthcare Conference, and final results at Euroanaesthesia meeting in May 2015 Phase 2 program expected to begin by Q2 2015 Planning for late 2016–2017 NDA/MAA submission
Slide 169: Innovative deal structure
170 Equity holder via series A June 2012 (along with Atlas Ventures and Partners Innovation Fund). Pre-negotiated option based on acceptable Proof of Concept study. Option is to acquire all assets and intellectual property for approximately $30M plus milestones and royalties. Innovative deal structu
Slide 170: Unmet needs and first-in-class solutions
Unmet needs for global atherosclerosis epidemic Relentless demand for solutions to increasing multidrug resistance 284 million surgeons worldwide demand safer, more efficient anesthesia First-in-class solutions for large-scale global healthcare problems Questions, answers and summary Scott Johnson
Slide 171: Growth drivers ahead summary
172 Unmet needs for global atherosclerosis epidemic Relentless demand for solutions to increasing multidrug resistance Surgeons worldwide demand safer, more efficient anesthesia Potential first-in-class solutions for large-scale global healthcare problems Growth drivers ahead Summary I Growth driver
Slide 172: Business strategy
Business strategy Glenn Sblendorio The Medicines Company
Slide 173: Strategy for growth
174 Strategy for growth Innovation: Strategic and operating leverage Situation Strategy Actions 1 Customers demand value Lead with purpose Build value-based solutions 2 Near-term growth demand Launch new products strongly Emphasize US market 3 ANGIOMAX® IP complexity Steadfast commitment Manage liti
Slide 174: Lead with purpose: build value-based solutions
175 Lead with purpose Action 1: Build value-based solutions ANGIOMAX® ORBACTIV™ IV anti-thrombin for PCI (incl. ACS in EU) 1 Decreased bleeding, non-inferior ischemic benefit vs. Heparin +/- GPI2 Linear PK/PD allows early sheath pull3 Reduced cost of complications, LOS Hospital decrease in cost $791
Slide 175: Launch new products strongly; focus on US market
176 US EU China Japan ROW Relative Market Opportunity Regulatory Market Access Market Challenges Growth Targeted Key Accounts (approx.) MDCO 1500 250 0 0 0 Potential Partners 0 1250 1200 450 Selective Strategy Full Attention Focused Attention Targeted Partnering Targeted Partnering Opportunistic Str
Slide 176: Steadfast commitment to ANGIOMAX
177 Strategy: Steadfast commitment to ANGIOMAX® Action 3: Manage litigation, lifecycle and partnerships I Growth drivers today II Growth drivers ahead III Business strategy IV What’s next Lifecycle ANGIOMAX® partnerships Continued defense of ANGIOMAX® patents Valuable supply contracts Teva Settled L
Slide 177: Build development-stage products and seek global partners
178 We are actively seeking regional partners for our registration-stage/launch products and anticipate dedicated efforts to build global partnerships in the future for our development-stage products Strategy: Build development-stage potentially major products Action 4: Achieve clinical POC and seek
Slide 178: In-licensing and acquisition strategy; potential payments
179 We have built our company based on an in-licensing and acquisition strategy which is disciplined, focused and milestone-based Milestones are tied to successful outcomes On aggregate, across current development and launch products we have paid <30% of total terms as upfront payments Potential nee
Slide 179: Potential payments if programs succeed
180 If all of our programs are successful and if we achieve success in development, regulatory and/or commercial launch milestones and consummate two acquisitions during 2015, then we anticipate paying up to $415M Potential need for capital if portfolio continues successfully Action 5: Drive product
Slide 180: Revenue target ranges and milestone payments
181 Potential need for capital if portfolio continues successfully Action 5: Drive products to success, pursue partnership opportunities and additional financing, as needed Revenue Target Ranges1 ($M) $25-$199 $200-$499 $500-$999 $1,000+ Total Aggregate annual revenue2 $905 $3,110 $2,950 $2,500 $9,4
Slide 181: Questions and answers
Questions and answers Glenn Sblendorio
Slide 182: What's next
What’s next Clive Meanwell The Medicines Company
Slide 183: Thank you
THANK YOU