1. C-1 Safety Results S. aureus Bacteremia and Endocarditis Study Gloria Vigliani, M.D. Vice President, Medical Strategy Cubist Pharmaceuticals

2. C-2 Introduction Daptomycin is approved for use in complicated skin and skin structure infections Daptomycin is approved for use in complicated skin and skin structure infections – 4 mg/kg once daily S. aureus bacteremia and endocarditis study S. aureus bacteremia and endocarditis study – 6 mg/kg once daily

3. C-3 Background 150,000+ patients treated in commercial use 150,000+ patients treated in commercial use – No new toxicities Current labeling Current labeling – Monitoring muscle pain and weakness – Weekly CPK – Consider discontinuing statins Supportive data  6 mg/kg from 15 other trials Supportive data  6 mg/kg from 15 other trials – 414 subjects and patients

4. C-4 Safety Monitoring Baseline evaluation Baseline evaluation Daily visits during treatment Daily visits during treatment End of Therapy, Test of Cure, post-study visits End of Therapy, Test of Cure, post-study visits Collection of adverse events, labs, concomitant medications, diagnostics and procedures Collection of adverse events, labs, concomitant medications, diagnostics and procedures CPK 3x per week during treatment CPK 3x per week during treatment Data Safety Monitoring Board (DSMB) Data Safety Monitoring Board (DSMB)

5. C-5 Exposure to Study Treatment DaptomycinComparator Number of patients exposed120116 Study Drug Duration (days) Mean (range)17.7 (1-74)19.7 (1-57) Gentamicin use [n (%)]1 (<1)108 (93.1) Mean (range)4.0 (NA)4.4 (1-12) Safety Population

6. C-6 Overview of Adverse Events Patients with any Daptomycin N = 120 % Comparator N = 116 % Adverse event (AE)95.894.8 Drug-related AE35.042.2 Severe AE45.845.7 Serious AE (SAE)51.744.8 Drug-related SAE2.55.2 Deaths15.016.4 Study drug D/C due to AE16.718.1 Safety Population

7. C-7 Most Common (  10%) Adverse Events Safety Population Preferred Term Daptomycin N = 120 % Comparator N = 116 % Anemia12.515.5 Diarrhea11.718.1 Vomiting11.712.9 Constipation10.812.1 Nausea10.019.8 Hypokalemia9.212.9 Edema peripheral6.713.8 Headache6.710.3 Arthralgia3.311.2

8. C-8 Study Drug Discontinued Due to AE Daptomycin N = 120 n (%) Comparator N = 116 n (%) Withdrawal due to AE20 (16.7)21 (18.1) Withdrawal due to drug-related AE10 (8.3)13 (11.2) Drug-related Events Rashes and hypersensitivity reactions 3 (2.5)9 (7.8) CPK increased3 (2.5)0 Interstitial nephritis and renal failure1 (<1)4 (3.4) Cardiac arrest1 (<1)0 Vomiting1 (<1)0 Thrombocytopenia1 (<1)0 Safety Population

9. C-9 Skeletal Muscle Effects System Organ Class Daptomycin N = 120 n (%) Comparator N = 116 n (%) Musculoskeletal and connective tissue disorders 35 (29.2)42 (36.2) High Level Term Muscle pains1 (<1) Muscle related symptoms2 (1.7)6 (5.2) Other musculoskeletal symptoms23 (19.2)30 (25.9) Rhabdomyolysis*1 (<1)0 *CPK elevation, no clinical features of rhabdomyolysis reported Safety Population

10. C-10 Maximum CPK in Patients with CPK Elevation on Treatment *Maximum post-baseline CPK 5548 U/L Daptomycin N = 120 n (%) Comparator N = 116 n (%) Number of patients with CPK > 50011 (9.2)2 (1.7) Maximum CPK (U/L) > 500 - 10004 (3.3)1 (<1) > 1000 - 20003 (2.5)0 > 2000 - 30001 (<1) > 3000 - 40002 (1.7)0 > 4000 - 500000 > 5000*1 (<1)0 Safety Population

11. C-11 CPK Elevations Associated with Musculoskeletal AEs Pt ID Age/ Sex Baselin e CPK Max CPK CPK Resolve d Rx D/CComment 070 29/F 50847YesNo“Rhabdomyolysis” secondary to in- hospital heroin overdose, day 12 084 43/M 8335548Yes Osteoporosis on steroids, lower extremity weakness due to spinal cord compression 229 55/F 412977Yes DM, obesity, CAD, HTN, arrhythmia, TIA, on simvastatin. Upper extremity weakness, CPK 853 day 15

12. C-12 Renal Impairment Adverse Events Renal Impairment AE Daptomycin n/N (%) Comparator n/N (%) At least 1 AE8/120 (6.7) 21/116 (18.1) Age  65 years 2/30 (6.7)12/38 (31.6) At least 1 drug-related AE3/120 (2.5)13/116 (11.2) At least 1 SAE1/120 (<1.0)9/116 (7.8) SAE age  65 years 0/30 (0)6/38 (15.8) Discontinuations1/120 (<1.0)5/116 (4.3) Safety Population

13. C-13 Time to Decrease in Creatinine Clearance Wilcoxon p=0.003; Log-rank p=0.002 % Without Decrease in Creatinine Clearance Study Day 100 75 50 25 0 01020304050607080Daptomycin Comparator

14. C-14 AEs at > 10% Difference Between Treatment Groups in Patients Treated  28 Days System Organ Class Daptomycin N = 27 % Comparator N = 29 % Blood and lymphatic disorders22.234.5 Gastrointestinal disorders44.469.0 General and administrative disorders51.969.0 Infections and infestations55.669.0 Investigations25.944.8 Metabolism and nutrition disorders14.837.9 Musculoskeletal and connective tissue40.751.7 Nervous system disorders25.937.9 Renal and urinary disorders14.831.0 Reproductive system and breast disorders3.713.8 Safety Population

15. C-15 Safety Summary Daptomycin was well tolerated at a dose of 6 mg/kg administered once daily in patients with S. aureus bacteremia and endocarditis Daptomycin was well tolerated at a dose of 6 mg/kg administered once daily in patients with S. aureus bacteremia and endocarditis Skeletal muscle effects uncommon, reversible and can be monitored Skeletal muscle effects uncommon, reversible and can be monitored Comparator agents associated with significant renal toxicity Comparator agents associated with significant renal toxicity No new safety issues identified with dose of 6 mg/kg once daily for up to 4 to 6 weeks No new safety issues identified with dose of 6 mg/kg once daily for up to 4 to 6 weeks