bristol myerd squibb American Society of Clinical Oncology (ASCO) Highlights

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  • 1. ASCO 2008 Highlights * Investor Teleconference June 2, 2008 *American Society of Clinical Oncology, May 30 – June 3, 2008 Not For Promotional Use 1
  • 2. Comments will be about the Company’s future plans and prospects that may be forward-looking statements under the Private Securities Litigation Reform Act of 1995. We caution that actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Company’s most recent annual report on Form 10-K, periodic reports on Form 10-Q and current reports on Form 8-K. These documents are available from the SEC, the Bristol-Myers Squibb web site or from Bristol-Myers Squibb Investor Relations. While we may elect to update forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our estimates change. Not For Promotional Use 2
  • 3. ASCO 2008 Highlights – Agenda More than 100 Abstracts at ASCO 2008 Erbitux® SPRYCEL® Ipilimumab IXEMPRATM Brivanib CT-322 Not For Promotional Use 3
  • 4. ASCO Highlights – Erbitux Data presented from 64 abstracts covered a variety of tumor types Colorectal cancer (CRC) 22 ..... ............. Head and neck cancer 10 ...... ............. Upper GI cancer including pancreas, esophageal and gastric . . . . . . . . . . . . . . . . . . . 6 Non-small cell lung cancer (NSCLC) . . . . . 6 Other tumors 20 ................. ............. Two plenary presentations, a first at ASCO for any given drug: First-line NSCLC (FLEX): Improved survival in broad population KRAS in first-line CRC (CRYSTAL): Improved PFS in wild-type KRAS Not For Promotional Use 4
  • 5. Erbitux – FLEX Randomized, multi-center, Phase III study of cetuximab in combination with cisplatin/vinorelbine versus cisplatin/vinorelbine alone in the first-line treatment of patients with advanced NSCLC Primary endpoint: – Overall survival Secondary endpoints: – Response – Progression-free survival – Disease control – Quality of life – Safety Not For Promotional Use 5
  • 6. Erbitux – FLEX: Overall Survival 1-year survival Median OS CT + Cetuximab ▬ 11.3 months 47 % (n=557) CT ▬ Overall Survival (%) 10.1 months 42 % (n=568) HR = 0.871 (95% CI 0.762–0.996) p-value = 0.044 Months Patients at risk CT 568 383 225 134 48 0 CT + Cetuximab 557 383 251 155 53 3 p-value = stratified log-rank test (2-sided) Not For Promotional Use FLEX, Pirker, et. al., ASCO, 2008 6
  • 7. Erbitux – FLEX: Pre-specified subgroup analysis Survival benefit was seen across all major subgroups ECOG performance status Smoking status Histology Gender Age Tumor stage Not For Promotional Use 7
  • 8. Erbitux – FLEX: Overall Survival Major Treatment Group: Caucasians (n=946) Pre-specified Analysis Median OS (months) CT + Cetuximab CT HR [95% CI] 0.803 Caucasian 10.5 9.1 (n=946) [0.694–0.928] Adeno 0.815 12.0 10.3 (n=413) [0.649–1.023] 0.794 Squamous cell 10.2 8.9 (n=347) [0.626–1.007] 0.807 Other 9.0 8.2 (n=185) [0.584–1.115] Other: includes large cell, adenosquamous, undifferentiated Not For Promotional Use FLEX, Pirker, et. al., ASCO, 2008 8
  • 9. Erbitux – FLEX: Safety Profile Adverse Events CT + Cetuximab CT Grade 3/4 (n=548) (n=562) Any event 91 % 86 % Neutropenia 53 % 51 % Febrile neutropenia 22 % 15 % Anemia 14 % 17 % Acne-like rash (only grade 3)* 10 % <1% Diarrhea 5% 2% Infusion-related reactions 4 %** <1% Treatment-related deaths 3% 2% *There were no grade 4 skin reactions **Allergy/Anaphylaxis 3% Not For Promotional Use FLEX, Pirker, et. al., ASCO, 2008 9
  • 10. Erbitux – CRYSTAL KRAS Analysis CRYSTAL was a Phase III study in first-line metastatic CRC which compared cetuximab plus FOLFIRI to FOLFIRI alone. Results of the study showed that cetuximab plus FOLFIRI met the primary endpoint of increasing median duration of progression-free survival (PFS) over FOLFIRI alone A retrospective analysis investigated the impact on response rate and PFS of the KRAS mutation status of tumors in the first-line treatment of metastatic CRC treated with FOLFIRI ± cetuximab Not For Promotional Use 10
  • 11. Erbitux – Relating KRAS Status to Efficacy: Data Quality 1198 subjects (ITT) 587 subjects analyzed for KRAS mutation status 540 subjects: KRAS evaluable population 348 (64.4%) KRAS wild-type 192 (35.6%) KRAS mutant Group A: Group B: Group A: Group B: 172 (49.4%) 176 (50.6%) 105 (54.7%) 87 (45.3%) 171 subjects with events (49.1%) 101 subjects with events (52.6%) Cetuximab + FOLFIRI FOLFIRI Not For Promotional Use 11
  • 12. Erbitux – Relating KRAS Status to Efficacy: Primary Endpoint – PFS, KRAS Wild-Type 1.0 Progression-free survival estimate KRAS wild-type HR=0.68; p = 0.017 0.9 0.8 mPFS Cetuximab + FOLFIRI: 9.9 months mPFS FOLFIRI: 8.7 months 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 18 Months Cetuximab + FOLFIRI FOLFIRI Not For Promotional Use CRYSTAL, Van Cutsem, et. al., ASCO, 2008 12
  • 13. Erbitux – Relating KRAS Status to Efficacy: Primary Endpoint – PFS, KRAS Mutant 1.0 Progression-free survival estimate KRAS mutant HR=1.07; p = 0.47 0.9 0.8 mPFS Cetuximab + FOLFIRI: 7.6 months mPFS FOLFIRI: 8.1 months 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 0 2 4 6 8 10 12 14 16 Months Cetuximab + FOLFIRI FOLFIRI Not For Promotional Use CRYSTAL, Van Cutsem, et. al., ASCO, 2008 13
  • 14. Erbitux – Relating KRAS Status to Outcome: Most Common Grade 3/4 Adverse Events KRAS wild-type KRAS mutant Cetuximab + Cetuximab + FOLFIRI FOLFIRI FOLFIRI FOLFIRI N=105 (%) n=87 (%) n=173 (%) n=176 (%) Any 50.6 78.0 55.2 72.4 Neutropenia 16.5 25.4 23.0 21.9 Febrile neutropenia 0.6 0.6 0 3.8 Diarrhea 9.1 17.3 12.6 13.3 Vomiting 2.8 4.6 6.9 2.9 Fatigue 4.5 2.3 2.3 9.5 Acne like rasha 0 16.2 0 17.1 Infusion-related reactions 0 1.7 0 3.8 a There There was no grade 4 acne-like rash acne- Not For Promotional Use CRYSTAL, Van Cutsem, et. al., ASCO, 2008 14
  • 15. Erbitux – ASCO Key Takeaways FLEX First anti-EGFR to prolong survival in broad population of NSCLC patients Cetuximab added to first-line chemotherapy with cisplatin / vinorelbine demonstrated superior overall survival compared to chemotherapy alone in patients with advanced EGFR-expressing NSCLC Side effects were similar to those observed in previous trials and manageable with acne-like skin rash as the most common cetuximab-related side effect CRYSTAL KRAS Analysis First anti-EGFR to show additional PFS benefit in patients with wild-type KRAS CRC as first-line treatment in combination with chemotherapy The grade 3/4 adverse event profile was similar in the KRAS evaluable and overall populations Not For Promotional Use 15
  • 16. Erbitux – Milestones in Further Development Regulatory filings planned: First-line metastatic head & neck: EXTREME First-line advanced NSCLC: FLEX Phase III studies ongoing: Adjuvant and metastatic CRC Esophageal cancer Gastric cancer Locally advanced NSCLC Not For Promotional Use 16
  • 17. ASCO Highlights – SPRYCEL Data presented from 11 abstracts Chronic Myelogenous Leukemia (CML) 2nd-line indication − Long-term duration of response and survival in chronic phase CML: 80% progression-free survival at 2 yrs − Efficacy of 100mg once-daily SPRYCEL dose in patients with baseline BCR-ABL mutations Expanding into 1st-line CML − Updated results of Phase I/II study of SPRYCEL in patients with previously untreated CML First data in Solid Tumors – Phase II study of SPRYCEL in patients with castration- resistant (hormone-refractory) prostate cancer Not For Promotional Use 17
  • 18. SPRYCEL – Expanding into 1st-line CML Historical 12-month complete cytogenetic responses (CCyR) rate with imatinib ~65% Rapid CCyR with SPRYCEL in this Phase I/II study in patients with previously untreated CML are highly encouraging – 40 patients randomized to SPRYCEL either 50mg BID or 100mg QD – 26 of 26 (100%) evaluable patients achieved a CCyR by 12 months – 30 of 32 (94%) evaluable patients achieved a CCyR by 6 months Strong rationale for Phase III study in 1st-line CML, which is ongoing and recruiting rapidly Study SWOG–040, Cortes, et. al., ASCO, 2008 Not For Promotional Use 18
  • 19. SPRYCEL – First Data in Solid Tumors: Study Characteristics Phase II study of SPRYCEL in patients with castration-resistant (hormone-refractory) prostate cancer Progressive disease based on rising PSA Castrate levels of testosterone (<50ng/dL) No prior chemotherapy Composite primary endpoint – PSA response – bone scan response – disease control according to RECIST criteria Assessment of urinary N-telopeptide (UNTx) as a marker of bone metabolism 47 patients treated on 2 SPRYCEL BID regimens Not For Promotional Use 19
  • 20. SPRYCEL – First Data in Solid Tumors Encouraging evidence of SPRYCEL efficacy in patients with metastatic prostate cancer PSA: – 33 of 43 (77%) had an improved PSA doubling time – 18 of 43 (42%) had a decrease PSA velocity – 1 patient had a confirmed PSA response Bone scan: – 22 of 36 (61%) patients had stable or improved disease at 12 weeks Disease control: – 12 of 24 (50%) RECIST-evaluable patients had stable disease Bone Metabolism: – 32 of 39 (82%) with evaluable UNTx levels had a decrease from baseline Study is continuing with a QD regimen Rationale for – moving SPRYCEL into Phase III in prostate cancer – development of SPRYCEL in a variety of other solid tumors Study -085, Yu, et. al., ASCO, 2008 Not For Promotional Use 20
  • 21. SPRYCEL – Ongoing Development Upcoming regulatory filing: 2-year CML/Ph+ALL data for full approval of SPRYCEL Ongoing development programs: First-line CML in Phase III Solid tumors including – Prostate cancer, transitioning to Phase III – Breast cancer – Glioblastoma – CRC Hematologic malignancies including – Multiple myeloma – Chronic lymphocytic leukemia Additional data presentations: European Hematology Association (EHA), June 12-16, 18 abstracts Not For Promotional Use 21
  • 22. ASCO 2008 Highlights – Ipilimumab Data presented from 19 abstracts Advanced Malignant Melanoma . . . . . . . . . . . . . . . . . . . . 15 Metastatic Hormone-refractory Prostate Cancer . . . . 2 Pre-clinical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Outcome Research/Health Economics . . . . . . . . . . . . . . . 1 Not For Promotional Use 22
  • 23. ASCO 2008 Highlights – Ipilimumab Oral Presentations Advanced Malignant Melanoma: Ipilimumab showed efficacy, with encouraging median overall survival Novel efficacy findings for immunotherapy development: Immune activation precedes tumor shrinkage by weeks to months Prostate Cancer: Ipilimumab was generally well tolerated at the maximum dose tested in this study (10 mg/kg) +/- additional XRT in patients with hormone-refractory prostate cancer – Seven confirmed responses (19%) and one unconfirmed response (2.7%) as assessed by PSA Not For Promotional Use 23
  • 24. Ipilimumab – Phase II Advanced Melanoma Program: Study Characteristics Study 8: N = 155 Single-arm; 10 mg/kg Progression on or after previously approved or frequently used therapy Study 22: N = 217 3-arm: 10 mg/kg, 3 mg/kg, and 0.3 mg/kg Progression or intolerance to any prior therapy Study 7: N = 115 2-arm: 10 mg/kg + placebo vs 10 mg/kg + prophylactic budesonide Untreated or progression on or after any prior therapy Not For Promotional Use 24
  • 25. Ipilimumab – Best Objective Response Rate (BORR) (mWHO) Study 8 Study 22 Study 7 (N = 155) (N = 217) (N = 115) 10mg/kg + 10 mg/kg Dose schedule 10 mg/kg 10 mg/kg 3 mg/kg 0.3mg/kg placebo +budesonide BORR 5.8 11 4.2 0 15.8 12.1 (CR + PR), % (2.7-10.7) (4.9-20.7) (0.9-11.7) (0) (7.5-27.9) (5-23.3) (range) Disease 27.1 29.2 26.4 13.7 35.1 31.0 control rate, % BORR, best objective response rate; CR, complete response; PR, partial response; mWHO, manual analysis on World Health Organization guidelines Study -007, Weber, et. al., ASCO, 2008 Study -008, O’Day, et. al., ASCO, 2008 Not For Promotional Use Study -022, Wolchock, et. al., ASCO, 2008 25
  • 26. Ipilimumab – Median Overall Survival in 3 Phase II Studies Updated Analysis (All Randomized) Study 8 Study 22 Study 7 10 mg/kg + 10 mg/kg + 10 mg/kg 10 mg/kg 3 mg/kg 0.3 mg/kg placebo budesonide (n = 155) (n = 72) (n = 72) (n = 73) (n = 57) (n = 58) Median OS, 10.2 14.6 8.6 8.6 – – mos (95% CI) (7.3, –) (6.9, –) (6.9, 12.3) (7.7, 14.5) (11.5, –) (6.8, –) 1-year OS, % 47 53.4 38.2 40.4 59.1 58.8 (95% CI) (38.6, 55.6) (41.2, 63.7) (6.9, 12.3) (27.1, 53.8) (45.4, 72.2) (43.6, 70.3) Median F/U, 9.5 8.9 8.1 7.9 10.9 10.6 mos (range) (3.6-12.3) (0.4-15.9) (0.4-17.0) (0.5-19.9) (0.3-20.1) (0.6-22.3) Crossover to 17 25 23 ~ ~ ~ 10 mg/kg @ (24%) (35%) (32%) ~12 wks, n (%) Study -007, Weber, et. al., ASCO, 2008 Study -008, O’Day, et. al., ASCO, 2008 Not For Promotional Use Study -022, Wolchock, et. al., ASCO, 2008 26
  • 27. Ipilimumab – Kaplan-Meier Estimate for Overall Survival per Dosing Schedule 1.0 10 mg/kg cohort Median OS = 14.59 months 0.8 53.39% 1-year survival Proportion alive 0.6 0.3 mg/kg 0.4 Censored 3.0 mg/kg Censored 0.2 10 mg/kg Censored 0 0 2 4 6 8 10 12 14 16 18 20 Months Study -022, Wolchok, et. al., ASCO, 2008 Not For Promotional Use 27
  • 28. Ipilimumab – Four Patterns of Response Were Observed Response in baseline lesions Stable disease with slow, steady decline in total tumor burden Response after initial increase in total tumor burden Response in total tumor burden in the presence of new lesions Not For Promotional Use 28
  • 29. Ipilimumab – Immune-related Adverse Events Safety population 0.3 mg/kg 10 mg/kg 3 mg/kg (n=72) (n=71) (n=71) Severe Severe Severe (grade 3-4) (grade 3-4) (grade 3-4) Any – % 7.0 0 25.4 GI – % 2.8 0 15.5 Hepatobiliary – % 0 0 2.8 Endocrine – % 2.8 0 1.4 Skin – % 1.4 0 4.2 Bowel perforations – % 0 0 0 1.4* Drug-related deaths – % 0 0 * Death caused by grade 3 respiratory infection possibly related to treatment. Patient was a tobacco user with lung metastases Study -022, Wolchok, et. al., ASCO, 2008 Not For Promotional Use 29
  • 30. Ipilimumab – Summary: Melanoma Survival rates across the Phase II program were encouraging and consistent – Median range 10-15 months – ~50% alive at 1 year Early biological activity, but variable timeframe to evolve a measurable clinical effect Four patterns of response observed likely contributed to the observed OS rates, despite modest BORR per mWHO Immune-related AEs were manageable and reversible with prompt treatment using established guidelines or treatment withdrawal Conducting ongoing studies focused on overall survival to better quantify the benefit/risk profile for the compound Not For Promotional Use 30
  • 31. Ipilimumab – Ongoing Development Monotherapy – Adjuvant melanoma trial to be initiated shortly Combination with Chemotherapy – Phase II program in combination with carbo/taxol in lung cancer (SCLC and NSCLC) Combination with Radiation – Phase II study ongoing in prostate cancer Other combinations under exploration – Combination with GVAX – Combination with targeted therapies Not For Promotional Use 31
  • 32. ASCO 2008 Highlights – Summary Erbitux® – FLEX data showing improved overall survival in NSCLC – CRYSTAL KRAS analysis showing additional PFS benefit in CRC patients with wild-type KRAS SPRYCEL® – Data showing efficacy in first-line CML – First solid tumor data in prostate cancer supporting Phase III transition Ipilimumab – New data showing encouraging overall survival in advanced melanoma Not For Promotional Use 32
  • 33. ASCO 2008 Highlights * Investor Teleconference June 2, 2008 *American Society of Clinical Oncology, May 30 – June 3, 2008 Not For Promotional Use 33