1. Nab-paclitaxel Development in Gynecologic Malignancies Robert Coleman, MD, FACOG, FACS Director of Clinical Research Department of Gynecologic Oncology MD Anderson Cancer Center

2. Nab-paclitaxel Gynecologic Malignancy Trials with Enrollment Complete Study DescriptionPrincipal Investigator Status nab-paclitaxel in Platinum- Sensitive Ovarian Cancer M. Teneriello47 pts Published JCO 2009 nab-paclitaxel + Carboplatin in Platinum-Sensitive Ovarian Cancer B. Benigno38 pts / 1 active nab-paclitaxel in Recurrent or Persistent Platinum-Resistant Ovarian Cancer R. Coleman49 pts / 2 active Final data analysis pending Current data from 41 pts nab-paclitaxel + Avastin in Recurrent Platinum-Resistant Ovarian Cancer T. Tillmanns48 pts / 2 active

3. Primary endpoints: Response Rate Secondary endpoints: Progression Free and Overall Survival, Quality of Life, Safety Phase II Evaluation of Nab-paclitaxel in Platinum-Sensitive Patients with Recurrent Ovarian, Peritoneal, or Fallopian Tube Cancer Teneriello, JCO 2009 Key Eligibility Measurable disease by RECIST or elevated CA- 125 ( > 70 U/mL) Prior platinum-based chemotherapy Platinum treatment-free interval >6 months n=47 nab-paclitaxel 260 mg/m 2 on Day 1 q Q3W x 6 cycles or 8 cycles if patient achieved CR

4. Patient Characteristics Number of Patients Enrolled47 Age, mean (Range)66 (42 – 84) n% ECOG Performance Status 0 1 38 9 81 19 Prior Therapy Prior taxane Prior Chemotherapy > 12 months Prior Chemotherapy < 12 months Surgery 42 43 4 44 90 92 9 94 Site of Primary Disease Epithelial Ovarian Fallopian Tube Peritoneum 37 1 9 79 2 19 Stage at Baseline IC/IIB/IIC III/IIIA/IIIB IIIC IV 4 7 25 11 9 15 52 23 Teneriello JCO 2009

5. Efficacy Data 64% Response Rate with Nab-paclitaxel Monotherapy Total Number of Eligible/Treated Subjects44 n (%)95% CI Best Response Complete Response Partial Response Stable Disease SD > 6 months SD < 6 months Progressive Disease Clinical Benefit (CR + PR + SD > 6 months) Non-evaluable 15 (34%) 13 (30%) 14 (32%) 6 (14%) 8 (18%) 2 (5%) 34 (77%) 3 (20.1 – 48.1) (16.1 – 43.0) (18.1 – 45.6) (0 – 10.7) Time to Response, median (months) Range 1.3 (0.5 – 4.8) Duration of Response, median (months) Range 7.9 (2.7 – 17.6)(6.7 –10.5) Progression-free Survival, median (months)8.5 Teneriello JCO 2009

6. Safety Data: Adverse Events Most Common Grade 3/4 AEs All Grade n (%) Grade 3 n (%) Grade 4 n (%) Hematological Neutropenia20 (47%)6 (13%)5 (11%) Leukopenia7 (15%)6 (13%)-- Non-hematological Neuropathy6 (13%)4 (9%)-- Fatigue10 (22%)1 (2%)-- Diarrhea3 (7%)1 (2%)-- Abdominal pain2 (4%)1 (2%)-- Pneumonia2 (4%)1 (2%)-- Upper respiratory tract infection 2 (4%)1 (2%)-- Generalized weakness2 (4%)1 (2%)-- Alopecia40 (87%)-- Teneriello JCO 2009

7. Primary endpoints: Antitumor activity and safety Secondary endpoints: Progression-free survival and overall survival Phase II Study of nab-paclitaxel Plus Carboplatin in Patients with Recurrent Platinum-Sensitive Ovarian or Primary Peritoneal Cancer Benigno Key Eligibility Recurrent ovarian or primary peritoneal cancer Platinum-sensitive Measurable disease n = 41 nab-paclitaxel 100 mg/m 2 Days 1, 8, 15 q 28 days + Carboplatin AUC 5 or 6 Day 1 q 28 days x 6 cycles Continue nab- paclitaxel until progressive disease or PI-PT discretion

8. Patient Characteristics Number of Patients Enrolled40 (38 evaluable) Age, mean (Range)62 (42 - 81) n% ECOG Performance Status 0 1 35 5 87 13 Prior Therapy Prior taxane / platinum Prior chemotherapy > 12 months Prior chemotherapy < 12 months 40 14 25 100 35 63 Site of Primary Disease Epithelial Ovarian Fallopian Tube 39 1 98 2 Stage at Baseline IIB / IIC / IIIB IIIC IV 9 28 3 23 70 7 Benigno

9. Dosing Information Treatment Cycles Completed >18 cycles n (%) 13-17 cycles n (%) 7-12 cycles n (%) 6 cycles n (%) < 6 cycles n (%) Evaluable Patients 38 TOTAL 5 1 pt active 410145 Reason for Discontinuing Phys or Pt discretion Progressive disease Toxicitiy Type/ cycle 220220 220220 640640 10 3 1 (G4 neurotoxity cycle 6) 0 3 2 (G4 pneumonia cycle 5, G3 hem cycle 4) Benigno Carboplatin dose AUC 6 administered to first 9 patients After Grade 4 neutropenia in 3 patients, reduced carboplatin to AUC 5 20 patients discontinued treatment for reasons other than toxicity or disease progression

10. Safety Data: Adverse Events Most Common Grade 3/4 AEs Grade 3 n (%) Grade 4 n (%) Hematological Neutropenia14 (34%)3 (7%) Anemia4 (10%)-- Thrombocytopenia2 (5%)-- Non-hematological Fatigue13 (32%)-- Carboplatin reaction7 (17%)-- Nausea2 (5%)-- Constipation1 (2%)-- Fever1 (2%)-- Shortness of breath1 (2%)-- Neuropathy--1 (2%) Benigno

11. Efficacy Data: Survival Over 50% of patients alive at 1-year Survival Rates 1-Year 56% 2-Year 39% Until 9/18/2009, there are 18 patients alive, 21 are dead and one is UNK due to lost of FU, one still active on cycle 44 Benigno

12. Primary endpoints: Antitumor activity and safety Secondary endpoints: Progression Free and Overall Survival Phase II Evaluation of nab-paclitaxel in Recurrent or Persistent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Key Eligibility Recurrent or persistent ovarian, peritoneal, fallopian tube carcinoma Platinum-resistant or refractory Paclitaxel-resistant or refractory Measurable disease n = 49 nab-paclitaxel 100 mg/m 2 on Days 1, 8, 15 q 28 Treatment until disease progression or unacceptable toxicity R.Coleman

13. Patient Characteristics  Age: –50-59 15 (36.6%) –60-69 14 (34.1%) –30-49 7 (17 %) –70-79 5 (12.2%)  Performance Status: –028 (68.3%) –112 (29.3%) –2 1 ( 2.4%)  Prior Therapy –1 Reg.41 (100%) –Immunoth 1 –Hormonal 2  Race: –White30 (73.2%) –African American 8 (19.5%) –Hispanic 2 ( 4.9%) –Am Indian 1 ( 2.4%)  Site of Disease –Ovary35 (85.4%) –Fallopian Tube 1 ( 2.4%) –Peritoneum 5 (12.2%)  Grade –1 5 (12.2%) –2 2 ( 4.9%) –3 34 (82.9%)  Cell Type: –Serous Adeno 29 (72%) R.Coleman

14. Efficacy Data 23% Response Rate with nab-paclitaxel Monotherapy Responses reported in 41 of 49 patients:  8 patients still to be evaluated N% Responses Partial Response1123.4 Stable Disease1736.2 Progressive Disease1736.1 Indeterminate24.3 PFS > 6mo No3063.8 Yes1634.0 Pending12.1 R.Coleman

15. Status of Patients by Cycles Completed 55% of patients received more than 3 cycles # of Cycles Receivedn% R.Coleman

16. Efficacy Data: Overall Survival and Progression-free Survival R.Coleman  Progression-free Survival, median: 4.5 months  Overall survival, median: 18.5 months

17. Safety Data: Adverse Events  No grade 4 toxicities  Only 1 patient grade 3 neurosensory toxicity AE, adverse event Toxicity / Adverse Events 41 of 49 pts Maximum grade, no. of patients 1234 Hematological anemia20 (49%)17 (41%)1 (2%)0 (0%) neutropenia4 (10%)5 (12%) 0 (0%) leukopenia16 (39%)8 (20%)1 (2%)0 (0%) thrombocytopenia3 (7%)0 (0%) Non-hematological neurosensory11 (27%)3 (7%)1 (2%)0 (0%) constitutional20 (49%)10 (24%)0 (0%) gastrointestinal18 (44%)7 (17%)2 (5%)0 (0%) metabolic7 (17%)2 (5%) 0 (0%) pain10 (24%)0 (0%)2 (5%)0 (0%) R.Coleman

18. GOG Phase II Trials in Platinum-Resistant Ovarian Cancer: Active Agents (126 Queue) RegimennRRPFSMedian OSNumber of Cycles Toxicity Paclitaxel Weekly 80mg/m 2 4921%3.6 mo13 moUp to 13 cycles 5 patients discontinued for toxicity Docetaxel 100mg/m 2 q3w 5822.4%2.5 moNRANC: 75% Gr IV Febrile: 30% Dose reduction: 36% Neuro: 3 grade III Pemetrexed 900mg/m 2 q3w 5121%2.9 mo11.4 moGrade 3/4 neutropenia 42% leukopenia 25% nab- paclitaxel 100 mg/m 2 weekly D1, 8, 15 of q4w 48 7 not yet reported 2 active 23.4%4.5 mo18.5 mo2 Patients are still being treated Cycle 21 No Grade 4 toxicity No treatment related deaths

19. Primary endpoints: Duration of objective response, safety Secondary endpoints: Duration of progression-free survival, overall survival, quality of life Phase II Study of Nab-paclitaxel with Bevacizumab in Patients with Recurrent Platinum-Resistant Primary Epithelial Ovarian or Primary Peritoneal Cancer Tillmans Key Eligibility Recurrent or persistent ovarian, peritoneal cancer Platinum-resistant within 6 months Measurable disease n = 48 Nab-paclitaxel 100 mg/m 2 on Days 1, 8, 15 + Bevacizumab 10mg/kg Days 1, 15 Q28d Treatment until disease progression or unacceptable toxicity

20. Efficacy Data 48% response rate with Nab-paclitaxel + Bevacizumab Best Overall Response Not DonePDPRSD Treatment Cyclen%n%n%n% 41633.31939.61327.1 71633.32143.81122.9 101633.32245.81020.8 131633.32245.81020.8 16 33.32245.81020.8 191633.32245.81020.8 221633.32245.81020.8 251633.32245.81020.8 281633.32245.81020.8 EOS All Pts510.4816.72347.91225.0 EOS Pts off study126820.51846.11230.8 Tillmanns  Response rate: 48%  Stable Disease: 25%

21. Efficacy: Progression-free Survival  Median Progression-free Survival: 8.26 months Tillmanns

22. Safety Data: Grade 3 / 4 Adverse Events* Most Common Grade 3/4 AEs*All Grade n (%) Grade 3 n (%) Grade 4 n (%) Hematological Neutropenia13 (27%)5 (10%)-- Anemia11 (23%)1 (2%)-- Non-hematological Abdominal pain17 (35%)3 (6%)-- Bowel obstruction17 (35%)4 (8%)2 (4%) Cardiac disorder11 (23%)--1 (2%) Fatigue35 (73%)2 (4%)-- GU / renal7 (15%)1 (2%) Infections8 (17%)4 (8%)-- Metabolism disorders18 (38%)2 (4%)-- Other blood / lymphatic system disorders16 (33%)2 (4%)-- Other gastrointestinal disorders29 (60%)6 (13%)-- Vascular disorders12 (25%)3 (6%)-- Neuropathy14 (29%)-- * One Death, NOS Tillmanns

23. Phase II Single Agent Bevacizumab Efficacy and Safety GOG 170-D Burger et al N = 62 Cannistra et al* N = 44 ORR13 (21%)7 (15.9%) 6 Month PFS40.3%27.8% ≥ Grade 3 Toxicity GI Perforation-5 (11.4%) Thrombosis / Embolism 1 (1.6%) (Venous) 4 (9.0%) (3 Arterial 1 VTE) HTN6 (9.7%)6 (13.6%) Cerebral ischemia-1 (2.3%) Proteinuria1 (1.6%)- Death Suspected as Related to Bevacizumab -3 (6.8%) *Trial terminated prematurely due to incidence of GI perforation. Burger RA, et al. J Clin Oncol. 2007;25(33):5165-5167; Cannistra SA, et al. J Clin Oncol. 2007;25(33):5180-5186.

24. Nab-paclitaxel Gynecologic Malignancy Trials Ongoing Study DescriptionPrincipal Investigator Status nab-paclitaxel + GM-CSF in Platinum-resistant ovarian cancer R. Swensen8 of 30 patients enrolled Phase I Trial of Intraperitoneal nab-paclitaxel in the Treatment of Advanced Malignancies Primarily Confined to the Peritoneal Cavity M. Cristea2 of 20 patients enrolled nab-paclitaxel in Recurrent or Persistent Cervical Cancer D. AlbertsGOG 2-stage trial 1 st stage (24 pts) met RR to advance to 2 nd stage

25. Ovarian Cancer Treatment Paradigm Where does nab-paclitaxel fit into this treatment paradigm? Surgery Front-line Platinum-based regimen Non-platinum- based regimen 1 st relapsed Platinum- based regimen Platinum- sensitive Platinum- resistant Platinum-sensitive = >6 months before recurrence after front-line platinum-based chemo #3 #1 #3 #2 Platinum-resistant = <6 months before recurrence after platinum- based chemo Carbo + Taxol ± Avastin Non-platinum- based regimens Carbo + Taxol ± Avastin Carbo + Gemzar ± Avastin Carbo + Doxil Doxil + Trabectedin Doxil Hycamtin Doxil Hycamtin