1. EB-1 CUBICIN ® (daptomycin for injection) for S. aureus Bacteremia Including Those With Known or Suspected Endocarditis Anti-Infective Drugs Advisory Committee Meeting March 6, 2006

2. EB-2 Log-rank test, stratification on C MIN CPK breakpoint: Chi-Sq statistic: 22.380 with 1 df Significance level: p << 5 X10 -4 DAPTOMYCIN TOXICODYNAMICS Time to CPK Elevation * When C MIN was evaluated as a continuous variable using Cox proportional hazards regression, it was also significant, p = 0.02.

3. EB-3 Dose (mg/kg) P (C MIN ≥ 25.7 mg/L) P (↑CPK) 43.7% 370/99993.7% 67.3% (730/9999)6.0% 815.9% (1585/9999)9.3% 1024.5% (2448/9999)12.8% 1232.8% (3279/9999)16.1% RISK ASSESSMENT Dose and Probability of CPK Abnormalities Monte Carlo simulation (9,999 iterations) utilized to estimate the probability of daptomycin trough concentrations being ≥25.7 mg/L From the cSSI study (CID 2004:38:1673), overall CPK elevations = 2.8%; daptomycin treatment emergent drug related CPK elevations = 2.1 %; 1.4% of troughs exceeded 25.7 mg/L

4. EB-4 Success by Pathogen-specific Therapy vs Comparator Agent (ITT AC) Success by Pathogen-specific Therapy Success by Comparator Agent 20 45 14 43 33 74 34 70 33 74 28 60 20 45 14 44VancomycinSSP

5. EB-5 Success in Patients with Septic Pulmonary Emboli (ITT) Risk Factor Daptomycin N = 120 n/N (%) Comparator N = 115 n/N (%) Septic pulmonary emboli6/10 (60.0)6/13 (46.2) RIE6/10 (60.0)6/9 (66.7) MSSA3/6 (50.0)3/5 (60.0) MRSA3/4 (75.0) LIE00/3* cBAC-MSSA00/1 * MRSA in 2 and MSSA in 1 comparator patients

6. EB-6 Adjudication Committee Success in Patients who Completed Therapy (ITT EOT/TOC) Success Rate % 70 80 69 77 50 80 47 77

7. EB-7 Investigator Success in Patients who Completed Therapy (ITT EOT/TOC) 77 80 74 77 64 80 58 77 Success Rate %

8. EB-8 Duke Criteria Underestimate Endocarditis Definite IEPossible IENot IE Entry DxLIERIE 122514454 Final DxLIERIEcBACuBAC 183512161 16 cases (6 LIE, 10 RIE) of S. aureus IE (7%) Diagnosed On-study

9. EB-9 Vancomycin Pharmacokinetic Summary 53/115 comparator patients received vancomycin53/115 comparator patients received vancomycin –44 (83.0%) had trough levels reported –Mean vancomycin trough levels = 14.1 µg/mL

10. EB-10 Complicated Bacteremia with Bone and Joint Infections Daptomycin N = 21 Comparator N = 11 Pts with Bone and Joint Infectionsn (%) No. who received intervention prior to or during treatment 11 (52.4)9 (81.8) Success at End of Therapy10 (47.6)3 (27.3) Success at Test of Cure8 (38.1)2 (18.2)

11. EB-11 Adjudication Committee Success All Randomized Patients (ITT EOT, TOC AC) Daptomyci n N = 124 % Comparator N = 122 % Differences In Success Rates (95% CI) End of Therapy Success59.758.2 1.5% (-10.8, 13.8) Test Of Cure Success 42.739.33.4% (-8.9, 15.7)

12. EB-12 Follow-up of Patients with Emergence of Reduced Susceptibility to Daptomycin and Failure due to Persisting/Relapsing S. aureus Pt ID Baseline Pathoge n Final Dx Clinical Summary Dur Tx Intervention Follow-up Therapy Outcome 037MRSALIEMitral/aortic IE, pulmonary edema 7No surgeryVanco, mino Made DNR, Died 183MRSALIEMitral IE, stroke8No surgeryVanco, cefepime MOFS, Died 152MSSAcRIETricuspid IE, large pulmonary emboli/ cavities, prob SC osteo, tunnel infection 20PICC removed D18 after AE redness at exit site x 11 days; exit cx + MSSA Oxacillin, gent Comp abx d40P 212MRSAcBACIV port infection, ? septic thrombphlebitis 14Port removed D2, pocket inadequately debrided VancoComp abx d28P 105MRSAcBACSeptic arthritis23Knee asp D2, synovectomy D5, D20P when relapse diagnosed Vanco, CTX Comp abx d66P 136MRSAcBACUndiagnosed retroperitoneal abscess 35Abscess dx’d day 31, CT drainage attempted D32 Linezolid, Vanco Comp abx d60P

13. EB-13 Post-marketing Reports of CPK Elevation* (> 150,000 Patients Treated) AE ReportedNumber of Reports CPK elevation61 CPK elevation with rhabdomyolysis14 *Data through 11 December 2005; reference Periodic Safety Update Reports 1 through 9

14. EB-14 Rhabdomyolysis Case Definition *Adapted from “ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of Statins” (Pasternak et al, J Am Col Cardiology 2002;40(3):567-572) **“Controlled Comparison of Amikacin and Gentamicin” (Smith et al, NEJM 1977;296(7):349-353. CriteriaRequired *Marked CPK elevation (typically substantially >10X ULN) + **Creatinine elevation within 2 weeks of onset of symptoms or CPK elevation:  0.5 mg/dL if  3.0 mg/dL  1.0 mg/dL if > 3.0 mg/dL + Elevated urinary myoglobin OR Elevated serum myoglobin OR Brown urine +/-

15. EB-15 Postmarketing Reports of Rhabdomyolysis Age Sex Dose (mg/kg )HxStatinOnset CPK Max (U/L) Creat BL mg/d L Creat Max mg/dL Myo- globinSymptoms 71 M 6DMN153,9651.31.8Unk Muscle weakness and myalgia, 72 M 3.7 DM CRF Y106,698unk 2.2 to 2.6 Urine and serum Weakness and pain, rechallenge positive 52* M 6.4 Hep C ITP Held10 20,77 1 0.81.4Unk Generalized weakness and pain 65 M 4 DM CRI CHF CAD N4 23,03 5 1.74.7Unk Dyspnea, lethargy; elevated BNP cTnI, CK-MB 53* * F 6DMN10 21,24 3 0.92.7Urine Generalized muscular weakness *Echevarria K, Datta P, Cadena J et al. J Antimicrob Chemother 2005; 55: 599–600 **Kazory A, Dibadj K. Weiner ID. J Antimicrob Chemother advance access 12 Jan 2006

16. EB-16 Shifts in CrCl from Baseline to Worst Value Creatinine Clearance on Study Baseline CL cr (mL/min) 50 - 8030 - < 50< 30 Daptomycin (N = 120) > 801131 50 - 8052 30 - < 501 Comparator (N =116) > 802331 50 - 80144 30 - < 507 Note: Both central and local laboratory data are utilized; if both results were available on a given day, the central laboratory result was used in the analysis

17. EB-17 Safety and Efficacy With and Without Gentamicin Comparator without Gentamicin N = 8 n (%) Comparator with Gentamicin N = 108 n (%) Renal Impairment AE (Safety population) 0 (0)21 (19.4) Success at TOC (ITT population) 2 (25.0)46 (42.6) *Patient with LIE

18. EB-18 Safety and Efficacy With and Without Gentamicin *Patient with LIE Daptomyci n with Gentamici n N = 1* n (%) Comparator without Gentamicin N = 8 n (%) Comparator with Gentamicin N = 108 n (%) Renal Impairment AE (Safety population) 1 (100)0 (0)21 (19.4) Success at TOC (ITT population) 1 (100)2 (25.0)46 (42.6)

19. EB-19 CPK Adverse Events Across Dose and Study Study, DoseDaptomycinComparator cSSSI, 4 mg/kg Any event DC due to event 15/534 (2.8%) 1/534 (<1%) 10/558 (1.8%) 0 SAB/IE, 6 mg/kg Any event DC due to event 8/120 (6.7%) 3/120 (2.5%) 1/116 (<1%) 0 Other studies,  6 mg/kg Any event DC due to event 14/249 (5.0%) 6/279 (2.2%) 4/160 (2.5%) 2/160 (1.3%)

20. EB-20 IVPD Model: MRSA in Stationary Phase Simulated endocardial vegetations in an in vitro pharmacodynamic modelSimulated endocardial vegetations in an in vitro pharmacodynamic model MRSA strain at high inoculum (5 x 10 9 CFU / SEV)MRSA strain at high inoculum (5 x 10 9 CFU / SEV) Daptomycin exhibited rapid bactericidal activity against stationary phase MRSADaptomycin exhibited rapid bactericidal activity against stationary phase MRSA LaPlante AAC 2004 Gentamicin

21. EB-21 200 CA-MRSA MIC (µg/mL) % Susceptible MBC ( µ g/mL) 50%90%Range Daptomycin0.250.50.06-11000.06-1 Teicoplanin0.51.00.13-21000.13-4 Vancomycin120.13-21000.13-8 All CA-MRSA were SCCmec type IVAll CA-MRSA were SCCmec type IV 78% of CA-MRSA strains carried PVL78% of CA-MRSA strains carried PVL Tsuji ICAAC 2005

22. EB-22 S. aureus with Defined Virulence Factors MIC (μg/mL) Antimicrobial AgentRangeMIC 50 MIC 90 Daptomycin0.12 - 0.50.250.5 Oxacillin  0.06 - >8 0.254 Vancomycin  0.25 - 1 0.5 Daptomycin is active against S. aureus with defined virulence factors (n = 42), including:Daptomycin is active against S. aureus with defined virulence factors (n = 42), including: –Accessory gene regulator (agr) 1 to 4 –Hemolysins –Panton Valentine leukocidin (PVL) –Toxic shock syndrome toxin-1 (TSST-1) –Enterotoxins Thorne GM, et al. Poster TH-11, ISSSI 2004.

23. EB-23 In Vitro SEV Model Huang JAC 2006

24. EB-24 14 C-Daptomycin Penetration into Cardiac Vegetations 14 C-daptomycin diffuses into cardiac vegetations 14 C-daptomycin diffuses into cardiac vegetations –Daptomycin homogeneously distributes throughout all the vegetations examined –Diffusion within the vegetations was consistent between all vegetations Caron et al, AAC 1992

25. EB-25 Baseline and Post-baseline Isolates 3 Log 10 Reduction = Bactericidal Daptomycin (8 µg/mL) was bactericidal in vitro against all isolates after 4 hours 152 Patient Number (Daptomycin-treated) -7 -6 -5 -4 -3 -2 0 Log 10 Reduction at 4 Hours Baseline Post-baseline 212105037183136172