bristol myerd squibb American Society of Clinical Oncology (ASCO) Highlights
1. ASCO 2008 Highlights *
Investor Teleconference
June 2, 2008
*American Society of Clinical Oncology, May 30 – June 3, 2008
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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.
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3. ASCO 2008 Highlights – Agenda
More than 100 Abstracts at ASCO 2008
Erbitux®
SPRYCEL®
Ipilimumab
IXEMPRATM
Brivanib
CT-322
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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
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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
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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)
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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
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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
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FLEX, Pirker, et. al., ASCO, 2008 8
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
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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
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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
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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-
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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33. ASCO 2008 Highlights *
Investor Teleconference
June 2, 2008
*American Society of Clinical Oncology, May 30 – June 3, 2008
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