1 Efficacy and Safety of 3 Different IV Doses of Palonosetron for the Prevention of PONV in the Outpatient (Study 1) and Inpatient (Study 2) Settings Study 1 (Outpatients—US): Candiotti KA, et al. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo for preventing postoperative nausea and vomiting. Anesth Analg. 2008;107: Study 2 (Inpatients—Europe): Kovac A, et al. A randomized, double-blind study to evaluate the efficacy and safety of three different doses of palonosetron versus placebo in preventing postoperative nausea and vomiting over a 72-hour period. Anesth Analg. 2008;107: Keith Candiotti, MD Departments of Anesthesiology, Perioperative Medicine and Pain Management University of Miami Miami, Florida American Society of Anesthesiologists Annual Meeting October 20, 2008

Palonosetron PONV Trials Study funded by MGI/Eisai Study presented on behalf of all investigators involved in both trials. 2

Phase 3 Study Designs Study 1: Outpatients (US) Study 2: Inpatients (Europe) Patients Randomization Stratification Placebo vs PALO dosage Interactive voice response system PlaceboPALO mg/kg IV PALO mg/kg IV PALO mg/kg IV (1) n = 135 (2) n = 136 (1) n = 136 (2) n = 136 (1) n = 137 (2) n = 137 (1) n = 138 (2) n = 135 M/F pts undergoing elective laparoscopic abdominal or gynecological surgery Female pts undergoing elective gynecological or breast surgery  Hx of PONV/motion sickness  Non-smoking status  Gender  Hx of PONV/motion sickness  Non-smoking status  Type of surgery Two Randomized, Stratified, Double-blind, Parallel-group, Balanced, Placebo-controlled Multicenter Studies

4 Study 1: Outpatients (US)Study 2: Inpatients (Europe) Palonosetron (IV) Placebo0.025 mg/kg0.050 mg/kg mg/kgPlacebo0.025 mg/kg mg/kg mg/kg (n=135)(n=136)(n=137)(n=138)(n=136) (n=137)(n=135) Gender (female) Mean age (years) Hx of PONV/motion sickness Smoking status (non- smoker) Alcohol consumption (no) Gynecologic laparoscopy Abdominal laparoscopy Gynecologic surgery Breast surgery ASA status I ASA status II ASA status III Patient Demographics

5 (% of Patients) Placebo PALO mg IV PALO mg IV PALO mg IV Study 1: Outpatients (US) Male + hx PONV + non-smoker 4444 Female + hx PONV + non-smoker Female + hx PONV + smoker 1315 Female + no hx PONV + non-smoker Study 2: Inpatients (Europe) Hx no PONV/motion sickness + non-smoker 5453 Hx PONV/motion sickness + non-smoker Hx PONV/motion sickness + smoker Stratification: PONV Risk Factors There were no statistically significant differences in PONV risk factors in patients across all treatment groups.

6 Anesthesia Premeds –Midazolam 1-2 mg IV or fentanyl  g IV as needed Induction –Propofol mg/kg IV or thiopental mg/kg IV; methohexital mg/kg IV –Succinylcholine mg/kg IV; rocuronium mg/kg IV, cisatracuronium mg/kg IV, vecuronium mg/kg IV, or mivacurium mg/kg Maintenance –N 2 O 50-70% end tidal concentration, O % end tidal concentration –Rocuronium, cisatracuronium or vecuronium titrated as needed for muscle relaxation Inhalation agent –Isoflurane 0.4-3%, desflurane 2-6% or sevoflurane 1-3% end tidal concentration, titrated as needed Intraoperative opioid –Fentanyl 2-10  g/kg IV or sufentanil  g/kg, titrated as needed Muscle relaxant reversal –Neostigmine <or= 2.5 mg IV and glycopyrrolate mg IV as per usual clinical practice

7 Study Endpoints Primary endpoint for both studies Complete response* (CR) at 0-24 h and h (no emetic episodes and no rescue medication) Secondary endpoints for both studies † CR at additional time intervals Complete control (CR plus no more than mild nausea) Percentage of pts experiencing emesis Number of emetic episodes Severity of nausea Time to treatment failure Patient functional interference (Study 1 only) * P value adjusted for 3-dose comparison vs placebo [ P =0.05/3=0.0166] † Measured at 2, 6, 24, 48, and 72 h (all tested at P <0.05)

8 Complete Response ( No Emesis, No Use of Rescue Medication) * Statistically significant at P < (for primary analyses); analysis by logistic regression. † Statistically significant at P <0.05 (for secondary analyses); analysis by logistic regression. * † † Primary endpoints % of Patients † * * * Study 1 Study 2

9 Percentage of Patients With No Treatment Failure P = for palonosetron mg vs placebo. Time to treatment failure: time to first emetic episode and/or to first use of rescue meds. Patients who did not have treatment failure were censored at 72 hours. % of Patients With No Treatment Failure P = for palonosetron mg vs placebo. Study 1: Outpatients (US) Study 2: Inpatients (Europe) Hours PALO mg Placebo Hours 0 PALO mg Placebo

10 Nausea Severity * Statistically significant vs placebo at P <0.05 (Cochran-Mantel-Haenszel) h0-72 h Placebo PALO mg Placebo PALO mg % of Patients Evaluable for Nausea Severe Moderate Mild None * * PlaceboPALO mg 0-24 h Placebo PALO mg 0-72 h Study 1Study 2 * *

11 Percentage of Patients Without Functional Interference * (Study 1 Only) * Functional interference due to nausea and vomiting was measured utilizing a Modified Osoba Nausea and Emesis Module. Measurements were based on a 4-point Likert scale: 1 = not at all; 2 = a little; 3 = quite a bit; 4 = very much. The percentages provided above represent those patients with a score of 1 on any individual subscale. † P <0.05 (Mann-Whitney test for pair-wise comparisons of palonosetron vs placebo) AppetiteSleepPhysical activitiesSocial lifeEnjoyment of life % of Patients Without Interference 0-24 h PlaceboPALO mg † † †

12 Study 1: Outpatients (US) Adverse Events: n, % Placebo (n=137) PALO mg IV (n=136) PALO mg IV (n=138) PALO mg IV (n=136) Total treatment-related AEs13 (10%)12 (9%)15 (11%)9 (7%) Headache6 (4%)5 (4%)9 (7%)4 (3%) Constipation4 (3%)2 (2%)6 (4%)4 (3%) Study 2: Inpatients (Europe) Adverse Events: n, %(n=136) (n=137)(n=135) Total treatment-related AEs45 (27%)48 (29%)49 (29%)48 (29%) Bradycardia15 (9%)16 (10%)14 (8%)13 (8%) ECG QTc prolonged11 (7%)10 (6%)14 (8%)15 (9%) Most Frequent Treatment-related Adverse Events There were no statistically significant differences among treatment groups.

13 Changes in QTc Study 1: Outpatients (US) Mean change from baseline in QTc by Fridericia, msec Placebo (n=137) PALO mg IV (n=136) PALO mg IV (n=138) PALO mg IV (n=136) 15 minutes hours91011 Study 2: Inpatients (Europe) Mean change from baseline in QTc by Fridericia, msec (n=168) (n=169)(n=168) 15 minutes hours ECGs: In triplicate at baseline (screening) and as a single recording at 15 minutes and at 3-6 hours (Study 1) and 6 hours (Study 2) post-study drug administration. Independent blinded cardiologist reading with manual QT interval measurement. Results: At 15 minutes post-dose, QT prolongation was consistent across all treatment groups. At 3 to 6 hours post-dose (Study 1) and at 6 hours post-dose (Study 2), QTc intervals remained slightly increased from baseline values; however, they tended to normalize compared with the 15- minute results.

14 Overall Summary Dose-response trend observed with increasing doses of PALO A single IV dose of PALO (0.075 mg) : was effective in reducing PONV in both the inpatient and outpatient settings was superior to placebo (0-24 hours) for the primary endpoint (CR) reduced the severity of nausea compared with placebo Adverse events: no dose relationship, no differences vs placebo, consistent with those expected for the 5-HT 3 receptor antagonist class These benefits may: distinguish PALO as unique among the 5-HT 3 receptor antagonists address important unmet needs, including nausea control