1. Efficacy of BSI-201, a PARP Inhibitor, in Combination with Gemcitabine/Carboplatin in Triple Negative Metastatic Breast Cancer: Results of a Phase II Study Joyce O’Shaughnessy, 1,2,4 Cynthia Osborne, 1,2,4 John Pippen, 1,2,4, Debra Patt, 3,4 Christine Rocha, 5 Valeria Ossovskaya, 5 Barry M. Sherman, 5 Charles Bradley 5 1 Baylor Sammons Cancer Center, 2 Texas Oncology, Dallas, TX; 3 Texas Oncology Cancer Center, Austin, Texas; 4 US Oncology, Dallas, TX; 5 BiPar Sciences, Inc., Brisbane, CA

2. Disclosure Dr. O’Shaughnessy has no commercial relationships to disclose. 2

3. Replication Lesions Base excision repair PARP1 Mechanisms of DNA Repair Single Strand Breaks Nucleotide excision repair Base excision repair PARP1 Double Strand Breaks Non-homologous end-joining Homologous recombination BRCA1/BRCA2 Fanconi anemia pathway Endonuclease-mediated repair DNA DAMAGE Cell Death Environmental factors (UV, radiation, chemicals) Normal physiology (DNA replication, ROS) MAJOR DNA REPAIR PATHWAYS Chemotherapy (alkylating agents, antimetabolites) Radiotherapy DNA Adducts/Base Damage Alkyltransferases Nucleotide excision repair Base excision repair PARP1 Helleday et al. Nature Reviews. 2008; 8:193 3

4. BRCA-Deficient Cells are Sensitive to PARP Inhibition PARP inhibition selectively reduces viability and induces chromosomal aberrations in BRCA-deficient cells Adapted by permission from Macmillan Publishers Ltd: Farmer et al. Nature, 2005; 434:917, © 2005 Log surviving fraction Conc. PARP Inhibitor (M) Wild type BRCA1-/- + PARP Inhibitor (10 nM) + PARP Inhibitor (1000 nM) No Treatment BRCA1-Deficient Cells BRCA1+/- 4

5. Triple Negative Breast Cancer (TNBC) ER-negative, PR-negative, and HER2 not overexpressed ~15% of all breast cancers (~170,000 cases worldwide in 2008) 1,2 Aggressive natural history –Higher rates of symptomatic visceral and brain metastases –Median survival of 13 months after developing metastases 3,4 –30% patients develop metastatic disease 5 4 Lin NU et al. Cancer. 2008; 113:2638-45 5 Rody A et al. Breast. 2007; 16:235-40 1 Carey L et al. JAMA. 2006; 295:2492-502 2 Swain S. ASCO Annual Meeting. June 3, 2008 3 Kassam F et al. Clin Breast Cancer. 2009; 9:29-33 5

6. CharacteristicsHereditary BRCA1Triple Negative/Basal-Like 1,2,3 ER/PR/HER2 statusNegative TP53 statusMutant BRCA1 statusMutational inactivation*Diminished expression* Gene-expression patternBasal-like Tumor histology Poorly differentiated (high grade) Poorly differentiated (high grade) Chemosensitivity to DNA- damaging agents Highly sensitive TNBC Shares Clinical and Pathologic Features with BRCA1-Related Breast Cancers 3 Sorlie et al. Proc Natl Acad Sci U S A 2001;98:10869-74 4 Miyoshi et al. Int J Clin Oncol 2008;13:395-400 *BRCA1 dysfunction due to germline mutations, promoter methylation, or overexpression of HMG or ID4 4 1 Perou et al. Nature. 2000; 406:747-752 2 Cleator et al.Lancet Oncol 2007;8:235-44 6

7. Limited treatment options for metastatic TNBC –Most patients treated with adjuvant anthracycline, taxane, and cyclophosphamide –PFS ≤ 4 months with chemotherapy for metastatic disease 1 –Bevacizumab/paclitaxel improves PFS compared with paclitaxel alone 2 Rationale for gemcitabine/carboplatin in MBC –Synergistic antitumor activity between gemcitabine and carboplatin 3 –Active combination in MBC, with response rates from 21% to 53% 3,4 Current Treatment for TNBC 3 Hsiao LC and Russell CA. Oncology. 2004; 18:12 4 Loesch D Et al. Clin Breast Cancer. 2008; 8:178 7 1 Kassam F et al. Clin Breast Cancer. 2009; 9:29-33 2 Miller K et al. NEJM. 2007; 357:2666

8. PARP Inhibitor Mechanism of Action BRCA1 BRCA2 1. PLATINUM CHEMOTHERAPY Inflicts DNA damage via adducts and DNA crosslinking 2. PARP1 UPREGULATION Base-excision repair of DNA damage 3. INHIBITION OF PARP1 Disables DNA base-excision repair 4. REPLICATION FORK COLLAPSE Double strand DNA break CELL SURVIVAL CELL DEATH PARP1 BSI-201 Pt PARP1 8

9. Preclinical Evidence for Synergy: Combination of BSI-201 with Carboplatin or Gemcitabine BSI-201 potentiated antitumor effects of carboplatin and gemcitabine in the MDA-MB-468 triple negative breast cancer cell line BiPar Sciences, data on file CarboplatinGemcitabine [BSI-201] 0  M 50  M 100  M % Viable Cells 100 40 20 80 0 0 60 0 mM 25 mM 0 nM 5 nM 9

10. PARP Inhibitor-Based Therapy for TNBC Background and Rationale PARP1 –Upregulated in majority of triple negative human breast cancers 1 BSI-201 –Small molecule PARP inhibitor –Potentiates effects of chemotherapy-induced DNA damage –No dose-limiting toxicities in Phase I studies of BSI-201 alone or in combination with chemotherapy – Marked and prolonged PARP inhibition in PBMCs 1 BiPar Sciences, data on file 10

11. Phase II TNBC Study Trial Design –Multi-center, open-label, randomized safety and efficacy trial –1:1 randomization of gemcitabine/carboplatin with or without BSI-201 Primary Objectives –Clinical benefit rate (CBR = CR + PR + SD ≥ 6 months) of gemcitabine/carboplatin ± BSI-201 –Safety of BSI-201 Secondary Objectives –Overall response rate (ORR) –Progression-free survival (PFS) –Overall survival (OS) 11

12. Key Inclusion/Exclusion Criteria Histologically documented TNBC Metastatic breast cancer with measurable disease 0-2 prior chemotherapy regimens for metastatic disease No prior treatment with gemcitabine, carboplatin, cisplatin, or PARP inhibitor Stable brain metastases allowed ECOG PS 0 - 1 12

13. Phase II TNBC Study: Treatment Schema 21-Day Cycle * Patients randomized to gem/carbo alone could crossover to receive gem/carbo + BSI-201 at disease progression RANDOMIZE BSI-201 (5.6 mg/kg, IV, d 1, 4, 8, 11) Gemcitabine (1000 mg/m 2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) BSI-201 (5.6 mg/kg, IV, d 1, 4, 8, 11) Gemcitabine (1000 mg/m 2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) Gemcitabine (1000 mg/m 2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) Gemcitabine (1000 mg/m 2, IV, d 1, 8) Carboplatin (AUC 2, IV, d 1, 8) RESTAGING Every 2 Cycles Metastatic TNBC N = 120 13

14. Enrollment: October 2007 – March 2009 of 123 patients 74 of 116 treated patients are off study treatment as of data cutoff of March 31, 2009 Efficacy determined by investigator assessment and RECIST criteria Hazard ratios estimated from Cox proportional hazards regression model Evaluation of 120 patients provides 80% power with one- sided alpha of 0.05 to detect an increase in CBR from 0.45 in control arm to 0.67 in investigational arm Final data analyses will be performed in 4Q2009 Study Enrollment and Statistical Overview 14

15. Patient Characteristics Gem/Carbo BSI-201 + Gem/Carbo Randomized Patients, n6261 Age, median (range)52 (26-80)55 (34-76) Race, n (%) White African-American Asian Missing/Unknown 48 (77.4%) 12 (19.4%) 0 (0.0%) 2 (3.2%) 48 (78.7%) 9 (14.8%) 1 (1.6%) 3 (4.9%) ECOG PS, n (%) 0 1 Missing/Unknown 43 (69.4%) 15 (24.2%) 4 (6.5%) 42 (68.9%) 16 (26.2%) 3 (4.9%) Metastatic Sites,* n (%) Lung Liver Brain Bone Lymph Nodes 33 (53.2%) 27 (43.5%) 6 (9.7%) 22 (35.5%) 37 (59.6%) 38 (62.3%) 24 (39.3%) 2 (3.3%) 20 (32.8%) 38 (62.3%) Prior Therapies,* n (%) Neo/Adjuvant Metastatic: 1 prior 2 prior 38 (64.4%) 13 (22.0%) 8 (13.5%) 32 (56.1%) 19 (33.3%) 6 (10.5%) Bevacizumab Taxane Anthracycline Taxane & Anthracycline 5 (8.4%) 4 (6.7%) 32 (54.2%) 7 (12.2%) 12 (21.0%) 6 (10.5%) 32 (56.1%) *Includes patients dosed only (n = 59 and n = 57 for each arm, respectively) 15

16. PARP1 is Upregulated in TNBC Gene expression profiling showed that PARP1 was significantly upregulated in the majority of triple negative breast cancers (n = 50) PARP1 mRNA (Red Fluorescence Units Normalized to  -Glucoronidase) P < 0.0001 16

17. Preliminary Efficacy Results* Gem/Carbo (n = 44) BSI-201 + Gem/Carbo (n = 42) P-value Objective Response Rate n (%) 7 (16%)20 (48%)0.002 **Clinical Benefit Rate n (%) 9 (21%)26 (62%)0.0002 *Includes patients enrolled before September 30, 2008 and patients who had a confirmed response or disease progression **Clinical Benefit Rate = CR + PR + SD ≥ 6 months 17

18. Progression-Free Survival 18 BSI-201 + Gem/Carbo (n = 57) Median PFS = 6.9 months Gem/Carbo (n = 59) Median PFS = 3.3 months P < 0.0001 HR = 0.342 (95% CI, 0.200-0.584)

19. Overall Survival 19 BSI-201 + Gem/Carbo (n = 57) Median OS = 9.2 months 8 Gem/Carbo (n = 59) Median OS = 5.7 months P = 0.0005 HR = 0.348 (95% CI, 0.189-0.649)

20. Safety Summary No differences in hematologic or non-hematologic toxicities No differences in gemcitabine/carboplatin dose reductions between study arms 20

21. Safety – Hematologic Toxicity Gem/Carbo (n = 59) BSI-201 + Gem/Carbo (n = 57) Grade 2Grade 3Grade 4Grade 2Grade 3Grade 4 Anemia, n (%) 12 (20.3%) 7 (11.9%) 0 (0.0%) 15 (26.3%) 7 (12.3%) 0 (0.0%) Thrombocytopenia, n (%) 7 (11.9%) 6 (10.2%) 6 (10.2%) 4 (7.0%) 6 (10.5%) 7 (12.3%) Neutropenia, n (%) 7 (11.9%) 18 (30.5%) 13 (22.0%) 7 (12.3%) 18 (31.6%) 7 (12.3%) Febrile neutropenia, n (%) 0 (0.0%) 3 (5.1%) 1 (1.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) RBC treatment*, n (%) 5 (8.5%) 5 (8.5%) 2 (3.4%) 3 (5.3%) 5 (8.8%) 2 (3.5%) G-CSF Use, n (%) 6 (10.2%) 6 (10.2%) 3 (5.1%) 4 (7.0%) 5 (8.8%) 1 (1.8%) *Transfusion and/or EPO use 21

22. Gem/Carbo (n = 59) BSI-201 + Gem/Carbo (n = 57) Grade 2Grade 3Grade 4Grade 2Grade 3Grade 4 Nausea, n (%) 10 (16.9%) 2 (3.4%) 0 (0.0%) 7 (12.3%) 0 (0.0%) 0 (0.0%) Vomiting, n (%) 9 (15.3%) 0 (0.0%) 0 (0.0%) 4 (7.0%) 1 (1.8%) 0 (0.0%) Fatigue, n (%) 10 (16.9%) 6 (10.2%) 0 (0.0%) 10 (17.5%) 1 (1.8%) 0 (0.0%) Neuropathy, n (%) 2 (3.4%) 0 (0.0%) 0 (0.0%) 1 (1.8%) 0 (0.0%) 0 (0.0%) Diarrhea, n (%) 6 (10.2%) 1 (1.7%) 0 (0.0%) 1 (1.8%) 1 (1.8%) 0 (0.0%) Safety – Non-Hematologic Toxicity 22

23. Conclusions PARP1 was upregulated in most evaluated TNBC patients BSI-201 + gemcitabine/carboplatin was well tolerated and did not potentiate chemotherapy-related toxicities BSI-201 improved patients’ clinical outcomes –Clinical Benefit Rate (62% vs. 21%; P = 0.0002) –ORR (48% vs. 16%; P = 0.002) –Median PFS (6.9 months vs. 3.3 months; P < 0.0001) –Median OS (9.2 months vs. 5.7 months; P = 0.0005) Promising safety and efficacy data from this Phase II study justify further investigation of BSI-201 in a Phase III study 23

24. Phase III Metastatic TNBC Study Open-Label, Randomized Safety and Efficacy Trial of Gemcitabine/Carboplatin ± BSI-201 in Metastatic TNBC Primary Endpoints –Overall Survival –Progression-Free Survival Patients randomized to chemotherapy alone may crossover to receive BSI-201 at disease progression Planned Initiation: Late June 2009 For more information: http://www.BiParSciences.com 24

25. Acknowledgements Participating patients US Oncology investigators and research coordinators Karla Burgos, US Oncology Project Management Phase I investigators of BSI-201 who enabled this study –Anthony Tolcher –Elisabeth Heath –Scott Kopetz –Nancy Lewis –Patricia LoRusso –Monica Mita –Kyri Papadopoulos 25