1. CALYPSO Trial: Carboplatin & Pegylated Liposomal Doxorubicin (PLD) versus Carboplatin & Paclitaxel in Relapsed, Platinum- Sensitive Ovarian Cancer Pujade-Lauraine E et al. ASCO 2009; Abstract LBA5509. (Oral Presentation)

2. Source: Pujade-Lauraine E et al. ASCO 2009;Abstract LBA5509. Introduction Choice of treatment for relapsed ovarian cancer is dependent upon the interval since prior platinum-based therapy –Relapse within six months: platinum-resistant disease –Relapse > six months: platinum-sensitive disease Carboplatin/paclitaxel (CP) is a standard treatment in platinum-sensitive, relapsed ovarian cancer Due to risk of cumulative neuropathy and hair loss, other carboplatin-based combinations are needed Pegylated liposomal doxorubicin (PLD) is a rationale partner for carboplatin –PLD resulted in significant improvements in PFS and OS compared to topotecan in platinum-sensitive ovarian cancer (JCO 2001;19:3312) –Safety and efficacy (median PFS: 9.4 months) of carboplatin/PLD was demonstrated in a phase II trial (Ann Oncol 2007;18:263) Current study objectives: –Evaluate PFS and safety of carboplatin/PLD (CD) versus CP in patients with platinum-sensitive, relapsed ovarian cancer

3. CALYPSO: Open Label Phase III Non-Inferiority Study Design Eligibility  Ovarian, fallopian tube or extra- ovarian papillary serous cancer in late relapse (>6 mos) after 1st or 2nd-line platinum-based therapy  Previous taxane treatment Control arm: CP Paclitaxel 175 mg/m 2 IV d1 Carboplatin AUC 5 d1 Q21 days x 6* Experimental arm: CD PLD 30 mg/m 2 IV d1 Carboplatin AUC 5 d1 Q28 days x 6* R *or until disease progression in patients with SD or PR (N = 976) Source: Pujade-Lauraine E et al. ASCO 2009;Abstract LBA5509.

4. Progression-Free Survival: ITT (Median Follow-Up = 22 months) Source: With permission from Pujade-Lauraine E. ASCO 2009;Abstract LBA5509. CD N = 467 CP N = 509 Median PFS, mo11.39.4 HR (95% CI)0.82 (0.72, 0.94) Log-rank p-value (superiority) 0.005 P-value (non-inferiority) <0.001 1.0 0.8 0.6 0.4 0.2 0.0 0612182430 Months from Randomization Proportion not Progressing CD CP

5. Hematologic Toxicity Grade 3/4 toxicity CD (n = 464) CP (n = 500)p-value Neutropenia35%46%<0.01 Febrile neutropenia2%4%NS Thrombocytopenia16%6%<0.01 Bleeding0.6%0%NS Anemia8%5%NS Source: Pujade-Lauraine E et al. ASCO 2009;Abstract LBA5509. NS = not significant

6. Non-Hematologic Toxicity CD (n = 466) CP (n = 501) ToxicityGrade 2Grade 3/4Grade 2Grade 3/4 Nausea/vomiting*31%4%20%4% Arthralgia/myalgia*4%0%18%1% Hand-foot syndrome*11%2% 0% Mucositis*13%2%6%1% Cardiac disorders2%1%3%1% Alopecia*7%--84%-- Neuropathy*4%1% † 24%4% † Carboplatin hypersensitivity reaction* 3%2% † 10%9% † *P < 0.001; † Grade 3/5 Treatment discontinuation related to toxicity * : CD = 6% vs CP = 15% Source: Pujade-Lauraine E et al. ASCO 2009;Abstract LBA5509.

7. EORTC OV28: Quality of Life - Peripheral Neuropathy Score Over Time Source: With permission from Pujade-Lauraine E. ASCO 2009;Abstract LBA5509. Months from Randomization Randomization3691215 60 50 40 30 20 10 Mean QoL scale score Error bars: 95% CI Treatment Arm CD CP

8. Summary and Conclusions In relapsed, platinum-sensitive ovarian cancer carboplatin/pegylated liposomal doxorubicin (CD) was non-inferior to CP –18% reduction in risk of progression (HR = 0.82, p = 0.005) Overall survival data is immature CP associated with more severe toxicity (carboplatin hypersensitivity), alopecia and long-lasting toxicity (neuropathy) — more toxicity-related treatment discontinuation –CP = 15% vs CD = 6% (p < 0.001) CD associated with moderate, reversible hand-foot syndrome, more mucositis and more nausea/vomiting Overall, CD demonstrated a superior therapeutic index (benefit/risk ratio) versus the current standard CP CD offers an evidence-based option for patients with relapsed, platinum- sensitive ovarian cancer Source: Pujade-Lauraine E et al. ASCO 2009; Abstract LBA5509.