Cortés J et al. ASCO 2009; Abstract 1022. (Poster Discussion)

1. Pertuzumab Monotherapy Following Trastuzumab-Based Treatment: Activity and Tolerability in Patients with Advanced HER2-Positive Breast Cancer Cortés J et al. ASCO 2009; Abstract 1022. (Poster Discussion)

2. Introduction Pertuzumab, the first in a new class of HER2 dimerization inhibitors (HDIs), is a humanized monoclonal antibody and a potent inhibitor of HER-mediated signaling pathways Synergistic effects of trastuzumab and pertuzumab, thought to be driven by the complementary mechanisms of action, have been observed in preclinical xenograft studies In a Phase II trial (BO17929), the combination of trastuzumab and pertuzumab was active in two patient cohorts with HER2-positive metastatic breast cancer (MBC) with disease progression on trastuzumab Objective Response Rate = 24.2% (Gelmon, ASCO 2008) Following these promising results, the trial protocol was amended to allow recruitment of a third cohort of patients, assessing the activity of pertuzumab monotherapy in this clinical setting Current study objectives: Investigate the safety and efficacy of pertuzumab monotherapy in patients with HER2-positive MBC with disease progression on trastuzumab-based therapy as part of last treatment regimen Source: Cortés J et al. ASCO 2009;Abstract 1022.

3. Trastuzumab continually suppresses HER2 activity Flags cells for destruction by the immune system Does not inhibit HER2 dimerization Pertuzumab inhibits HER2 forming dimer pairs Suppresses multiple HER signalling pathways Flags cells for destruction by the immune system Trastuzumab and Pertuzumab Bind to Different Regions on HER2 HER2 receptor Pertuzumab Trastuzumab Dimerisation domain of HER2 Subdomain 4 of HER2 Source: With permission from Cortés J. ASCO 2009;Abstract 1022.

4. BO17929: Pertuzumab Monotherapy, Cohort 3 (N=29) • Eligibility: • HER2-positive MBC • ≤ 3 lines of prior cytotoxic therapies and/or trastuzumab (H), including adjuvant therapy • Disease progression during trastuzumab as most recent treatment • Study treatment initiated > 1 month after last dose of trastuzumab Cohort 3a: Pertuzumab (P) only (n=29) Cohort 3b: P + H(n=15) PD* P, 840 mg loading dose  420 mg q3w H, 4 mg/kg loading dose  2 mg/kg qw or 8 mg/kg loading dose  6 mg/kg q3w * Trastuzumab reintroduction allowed with documented disease progression during pertuzumab monotherapy

5. Results: Response and Clinical Benefit in Study Cohort 3 1 Cohort 3a: Patients in the third cohort on pertuzumab monotherapy 2 Cohort 3b: Patients in the third cohort who went on to receive pertuzumab and trastuzumab (H + P) *Number of patients evaluable for overall best response at data cut-off Source: Cortés J et al. ASCO 2009; Abstract 1022.

6. Adverse Events: BO17929 Cohort 3 • Most adverse events (AE) were grade 1/2 • Most frequent: Diarrhea, nausea and vomiting • One patient experienced a treatment-related grade 3 AE (fatigue) • Later downgraded to grade 2 unrelated to study treatment • Mean changes in LVEF did not indicate a fall versus baseline • Three patients had a falling LVEF • None have received treatment for this event and all were asymptomatic Source: Cortés J et al. ASCO 2009; Abstract 1022.

7. Summary and Conclusions • Pertuzumab monotherapy is active in patients with HER2-positive breast cancer with disease progression on trastuzumab • Trastuzumab/pertuzumab combination therapy is active in patients with disease progression on either trastuzumab or pertuzumab monotherapy • Pertuzumab monotherapy or in combination with trastuzumab was well tolerated. No clinically significant cardiac events were observed in this patient group • CLEOPATRA is a Phase III trial of trastuzumab + docetaxel ± pertuzumab in previously untreated HER2-positive metastatic breast cancer, and is open to recruitment Source: Cortés J et al. ASCO 2009; Abstract 1022.