bristol myerd squibb 26th Annual JPMorgan Healthcare Conference

1Not for promotional useNot for promotional use

Research & DevelopmentResearch & DevelopmentUpdateUpdate

Elliott Sigal, MD, PhDElliott Sigal, MD, PhDExecutive Vice PresidentExecutive Vice President

Chief Scientific Officer & President, R&DChief Scientific Officer & President, R&D

JP Morgan Healthcare ConferenceJanuary 7, 2008


During this meeting, we will make statements about the CompanyDuring this meeting, we will make statements about the Company’’s future s future plans and prospects, including statements about our financial poplans and prospects, including statements about our financial position, sition, business strategy, research pipeline concerning product developmbusiness strategy, research pipeline concerning product development and ent and product potential, that constitute forwardproduct potential, that constitute forward--looking statements for purposes looking statements for purposes of the safe harbor provisions under the Private Securities Litigof the safe harbor provisions under the Private Securities Litigation Reform ation Reform Act of 1995.Act of 1995.

Actual results may differ materially from those indicated by theActual results may differ materially from those indicated by these forwardse forward--looking statements as a result of various important factors, inclooking statements as a result of various important factors, including those luding those discussed in the companydiscussed in the company’’s most recent annual report on Form 10s most recent annual report on Form 10--K, K, periodic reports on Form 10periodic reports on Form 10--Q and current reports on Form 8Q and current reports on Form 8--K. These K. These documents are available from the SEC, the Bristoldocuments are available from the SEC, the Bristol--Myers Squibb websiteMyers Squibb websiteor from Bristolor from Bristol--Myers Squibb Investor Relations.Myers Squibb Investor Relations.

In addition, any forwardIn addition, any forward--looking statements represent our estimates only as looking statements represent our estimates only as of today and should not be relied upon as representing our estimof today and should not be relied upon as representing our estimates as of ates as of any subsequent date. While we may elect to update forwardany subsequent date. While we may elect to update forward--looking looking statements at some point in the future, we specifically disclaimstatements at some point in the future, we specifically disclaim any any obligation to do so, even if our estimates change.obligation to do so, even if our estimates change.


AgendaAgenda

Evolving to the Next Generation Evolving to the Next Generation BioPharmaBioPharma ModelModel

R&D StrategyR&D Strategy

Pipeline UpdatePipeline Update


Forces Driving Industry ChangeForces Driving Industry Change

Increased regulatory / clinical requirements Increased regulatory / clinical requirements

Decreased access to physicians by sales Decreased access to physicians by sales modelmodel

Increased power of payers on pricing and Increased power of payers on pricing and prescribingprescribing

Consolidation / costConsolidation / cost--reduction across reduction across industryindustry


Evolution of Biotech and Pharmaceutical Evolution of Biotech and Pharmaceutical CompaniesCompanies

Traditional Biotech

Traditional Large Pharma

MajorBiotechs

’’80s/80s/’’90s90s 2000 2000 –– now now

SmallBiotechs

Mid-CapPharma

MegaPharma

Next Generation

Model

Future ModelFuture Model

More More consolidation?consolidation?

More More consolidation?consolidation?

Focus on Focus on productivity/productivity/

executionexecution


Next Generation Next Generation BioPharmaBioPharma ModelModel

Next GenerationBioPharma

Best of PharmaBest of Biotech

Innovative Innovative PortfolioPortfolio

Selectively Selectively Integrated Integrated

Business ModelBusiness ModelContinuous Continuous

ImprovementImprovement

Nimble and Entrepreneurial Culture


Innovative PortfolioInnovative Portfolio

Selectively Selectively IntegratedIntegrated

Business ModelBusiness ModelContinuousContinuous

ImprovementImprovementInnovativeInnovativePortfolioPortfolio

Innovative Portfolio: Implications to R&DFocus is on serious unmet medical needs in specialty and high prevalence disease areasFlexibility to choose the right modality for the right target Generation of clinical and economic data that demonstrate value for payers and patients



2

1

3

1

2

2

4

6

4

6

1

2

2

4

4

5

3

1

4

1

5

2

0 1 2 3 4 5 6 7 8 9 10 11

J&J

Wyeth

AZ

Roche*

Lilly

S-A

Novartis

GSK

BMS

Merck

Pfizer

PriorityNon-Priority

Record of Priority Review is External Record of Priority Review is External Validation of Innovative PortfolioValidation of Innovative Portfolio Average FDAAverage FDA

Review TimeReview Time(Months)(Months)

1919

88

77

1414

1818

2323

1818

1010

1515

1616

1111

US NME Approvals January 2002 US NME Approvals January 2002 –– October 2007 October 2007 with FDA Review Status and Average Review Timewith FDA Review Status and Average Review Time

Note: Includes compounds designated as classification “1” (NDA chemical type – new molecular entity) by the FDA. Novel biologics and novel vaccines are included.* Includes compounds Genentech filed in the US (i.e., Avastin, Tarceva) for which Roche had significant development participation.Approval for Boniva credited to both Roche and GSK based on co-development agreement.Source: PhRMA, FDA, Company Reports, BMS internal analysis

$7.2$7.2

$4.5$4.5

$6.2$6.2

$4.3$4.3

$5.6$5.6

$3.0$3.0

$5.0$5.0

$2.9$2.9

$3.8$3.8

$4.7$4.7

20062006PharmaPharma

R&D Spend R&D Spend ($B) ($B)

$2.8$2.8





Selectively Integrated Business ModelSelectively Integrated Business Model

Selectively Integrated Business Model:Implications to R&D

External sources of innovation to complement internal capabilitiesCo-development and co-commercialization partnershipsFocusing internal activities in core, high-value areas



CoCo--development and Codevelopment and Co--commercialization to commercialization to Optimize the Value of a PipelineOptimize the Value of a Pipeline

Share risk and cost associated with large lateShare risk and cost associated with large late--stage development investmentsstage development investments

Allow greater investment in broader portfolioAllow greater investment in broader portfolio

Make big products even bigger by leveraging Make big products even bigger by leveraging partnerpartner’’s capabilities s capabilities

SaxagliptinSaxagliptinApixabanApixaban DapagliflozinDapagliflozin





Focus on Continuous ImprovementFocus on Continuous Improvement

Focus on Continuous Improvement: Implications to R&D

Improving yield Increasing cost-effectiveness



Nine New Drug Approvals inNine New Drug Approvals inLess Than Five YearsLess Than Five Years

20032003 20042004 20052005 20062006 20072007

Otsuka AmericaPharmaceutical, Inc.

ImClone SystemsIncorporated

HIV / AIDS

Schizophrenia, Depression

Cancer

Hepatitis B

Rheumatoid ArthritisHIV / AIDS

Cancer

Cancer

Depression

SomersetPHARMACEUTICALS INC.


BristolBristol--Myers Squibb R&D Productivity Myers Squibb R&D Productivity Counter to Industry TrendCounter to Industry Trend

Industry based on top 11 pharma companies Industry based on top 11 pharma companies Source: Company reports, PhRMA, BMS internal analysisSource: Company reports, PhRMA, BMS internal analysis

Rolling 3 year totals for Pharma R&D spend vs. U.S. NME approvalRolling 3 year totals for Pharma R&D spend vs. U.S. NME approvalss

$ B

illio

ns$

Bill

ions

$0$0

$1$1

$2$2

$3$3

$4$4

$5$5

$6$6

$7$7

$8$8

$9$9

$10$10

19961996--19981998 19971997--19991999 19981998--20002000 19991999--20012001 20002000--2002200200

11

22

33

44

5566

77

88

99

1010

1111

1212Industry AvgIndustry AvgBMSBMS

3 Yr Pharma R&D Spend3 Yr Pharma R&D Spend 3 Yr R&D NME Approvals3 Yr R&D NME ApprovalsIndustry AvgIndustry AvgBMSBMS

19991999--20012001 20002000--20022002 20012001--20032003 20022002--20042004 20032003--20052005R&D Spend:R&D Spend:

NME Approvals:NME Approvals:20012001--2003200320042004--20062006

NM

E A

ppro

vals

NM

E A

ppro

vals


Continuous Productivity Occurring Continuous Productivity Occurring CompanyCompany--widewide

Productivity Transformation Team

Management Council

Supply ChainSupply Chain R&DR&D Commercial Commercial OperationsOperations

G&AG&A

$1.5 BillionCost Savings + Cost Avoidance

$400 MM$400 MM $200 MM$200 MM $550 MM$550 MM $350 MM$350 MM


AgendaAgenda

Evolving to the Next Generation Evolving to the Next Generation BioPharma ModelBioPharma Model

R&D StrategyR&D Strategy

Pipeline UpdatePipeline Update


Building Pipelines Within Products: Building Pipelines Within Products: Full Development ProgramsFull Development Programs

A new cytotoxic designed to overcome resistance

IpilimumabEstablishing a new

immunotherapy paradigm for the treatment of cancer

BelataceptNovel co-stimulation blocker

developed to replace cornerstone therapy in solid

organ transplantation

SaxagliptinBringing a new choice

to the management of diabetes – driven by the partnership of

Bristol-Myers Squibband AstraZeneca

DapagliflozinProviding a new insulin-

independent mechanism for improved outcomes in overweight and obese

diabetes patients

ApixabanPredictable and reliable

anticoagulant with a wider therapeutic window than current standard of care














diabetes patients




Current Therapies for Solid Organ TransplantCurrent Therapies for Solid Organ Transplant

Significant gains in oneSignificant gains in one--year graft survival rates with year graft survival rates with current therapy current therapy

Less progress on fiveLess progress on five--year patient and graft survivalyear patient and graft survival–– 34% graft loss for deceased donors34% graft loss for deceased donors–– 21% graft loss for living related donors21% graft loss for living related donors

Calcineurin inhibitors (CNIs) are associated withCalcineurin inhibitors (CNIs) are associated withlonglong--term complications term complications

–– Increased risk of chronic allograft nephropathy Increased risk of chronic allograft nephropathy leading to graft loss leading to graft loss

–– Increased risk factors for cardiovascular diseaseIncreased risk factors for cardiovascular disease–– Increased risk of diabetesIncreased risk of diabetes


Belatacept Showed Comparable Efficacy and Belatacept Showed Comparable Efficacy and Improved Safety Over Cyclosporine at 1 YearImproved Safety Over Cyclosporine at 1 YearImmunosuppressive Efficacy Immunosuppressive Efficacy

Low rates of acute rejection, comparable across armsLow rates of acute rejection, comparable across armsComparable patient and graft survivalComparable patient and graft survival

Safety ProfileSafety ProfileLow rates of serious infections and malignancies, Low rates of serious infections and malignancies, comparable across armscomparable across arms

Addressing Key Areas of Unmet NeedAddressing Key Areas of Unmet NeedProtection of renal function Protection of renal function Lower rates of chronic allograft nephropathyLower rates of chronic allograft nephropathyFavorable trends in CV and metabolic parametersFavorable trends in CV and metabolic parameters

Phase II Study IM103-100, 12 month results, NEJM, 353:770, August 25, 2005Phase II Study IM103Phase II Study IM103--100, 12 month results, NEJM, 353:770, August 25, 2005100, 12 month results, NEJM, 353:770, August 25, 2005


Cal

cula

ted

GFR

(Glo

mer

ular

Filt

ratio

n R

ate)

C

alcu

late

d G

FR (G

lom

erul

ar F

iltra

tion

Rat

e)

(ml/m

in/1

.73m

(ml/m

in/1

.73m

22 ))

Months After TransplantMonths After Transplant

Belatacept Showed Stable Kidney Belatacept Showed Stable Kidney Function Over Four YearsFunction Over Four Years

1212 1818 2424 3030 3636 4242 4848

Belatacept (N = 102) Belatacept (N = 102) Cyclosporine (N = 26)Cyclosporine (N = 26)

9090

8080

7070

6060

Oral Presentations: 2007 ATC, San Francisco; 2007 ESOT, Prague Oral Presentations: 2007 ATC, San Francisco; 2007 ESOT, Prague


Belatacept: Initial Registrational Program Belatacept: Initial Registrational Program in Renal Transplantin Renal Transplant

Planning for BLA submission in 1H 09Planning for BLA submission in 1H 09

StudyStudy Study DesignStudy Design EndpointsEndpoints NN

BroadBroad--criteria criteria donordonor

belatacept vs. belatacept vs. cyclosporinecyclosporine

belatacept vs. belatacept vs. cyclosporinecyclosporine

660660

ExtendedExtended--criteria donorcriteria donor

540540

••Death/Graft LossDeath/Graft Loss••Renal function (GFR)Renal function (GFR)••Acute rejectionAcute rejection••Chronic allograft Chronic allograft nephropathynephropathy














diabetes patients




Saxagliptin: DPP4 Inhibition Saxagliptin: DPP4 Inhibition –– An Emerging An Emerging Mechanism for Diabetes TreatmentMechanism for Diabetes Treatment

Once a day, oral route of administrationOnce a day, oral route of administrationWeight neutral and low incidence of hypoglycemiaWeight neutral and low incidence of hypoglycemiaIn clinical trials, safety profile comparable to In clinical trials, safety profile comparable to placeboplaceboProlonged glycemic control at low dose due to:Prolonged glycemic control at low dose due to:

–– Highly potent inhibition of DPP4Highly potent inhibition of DPP4–– Sustained binding to DPP4 active siteSustained binding to DPP4 active site

FixedFixed--dose combinations facilitated by:dose combinations facilitated by:–– Unique formulationUnique formulation–– Efficacy at low doseEfficacy at low dose


Saxagliptin + Metformin Show Improved Saxagliptin + Metformin Show Improved HbAHbA1c1c Reductions at Week 24Reductions at Week 24

* p<0.0001* p<0.0001Bars indicate 95% twoBars indicate 95% two--sided confidence intervalsided confidence intervalPhase III Study Phase III Study --014, ADA, June 2007014, ADA, June 2007

Adjusted Change From BaselineDifference in Adjusted Change from Baseline vs Placebo + Metformin

% C

hang

e in

HbA

% C

hang

e in

HbA

1c1c

PBOPBO+ MET + MET

(N = 175)(N = 175)

SAXA 2.5mgSAXA 2.5mg+ MET+ MET

(N = 186)(N = 186)

SAXA 5mgSAXA 5mg+ MET + MET

(N = 186)(N = 186)

SAXA 10mgSAXA 10mg+ MET+ MET

(N = 180)(N = 180)

*-1

* *-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

--0.730.73 --0.720.72--0.830.83


Saxagliptin Registrational ProgramSaxagliptin Registrational Program

NDA submission targeted for 1H 08NDA submission targeted for 1H 08Target indicationsTarget indications

–– MonotherapyMonotherapy–– AddAdd--on combination therapy on combination therapy

(metformin, TZD, sulfonylurea)(metformin, TZD, sulfonylurea)–– Initial combination therapy with Initial combination therapy with

metforminmetforminPhase III data presentationsPhase III data presentations

–– ADA, June 2008ADA, June 2008–– EASD, Sept 2008EASD, Sept 2008














diabetes patients




PropertiesProperties BenefitsBenefits

Orally active Ease of administration

Rapid onset of action Obviates need for overlap with a parenteral anticoagulant

No food or drug interactions Simplified dosing

Predictable anticoagulant effect

No routine coagulation monitoring

Extra-renal clearance Safe in patients with renal insufficiency

Rapid offset of actionSimplifies management in case of bleed or need for intervention

Optimal benefit/risk profile Treatment benefit outweighs risk

Apixaban target profile

Properties of an Ideal AnticoagulantProperties of an Ideal Anticoagulant


(mg)(mg)

0

5

10

15

20

25

30

35

40

Daily Dose: 5 10 20 Daily Dose: 5 10 20 5 10 20 5 10 20 QD BID QD BID QD BID QD BID QD BID QD BID QD BID QD BID QD BID QD BID QD BID QD BID Enox WarfEnox Warf Enox WarfEnox Warf

% o

f Pat

ient

s%

of P

atie

nts

Phase II VTE Prevention Study: APROPOS (CV185010), ASH December Phase II VTE Prevention Study: APROPOS (CV185010), ASH December 20062006

Apixaban Demonstrated Greater Efficacy in Preventing Apixaban Demonstrated Greater Efficacy in Preventing VTE / Death Than Standard of Care (Phase II Study)VTE / Death Than Standard of Care (Phase II Study)

ApixabanApixaban ApixabanApixabanBID dosing consistently produced lower rates of VTE/death BID dosing consistently produced lower rates of VTE/death compared with QD dosing with comparable bleeding ratescompared with QD dosing with comparable bleeding rates

VenousVenousThromboembolism (VTE) / Thromboembolism (VTE) /

DeathDeathTotal BleedingTotal Bleeding


Indication Indication PhasePhase Trial NTrial NVTE prevention (knee replacement)VTE prevention (knee replacement) IIIIII ADVANCEADVANCE--11 3,0003,000

VTE prevention (knee replacement)VTE prevention (knee replacement) IIIIII ADVANCEADVANCE--22 3,0003,000

VTE prevention (hip replacement)VTE prevention (hip replacement) IIIIII ADVANCEADVANCE--3 3 4,0004,000

VTE prevention (medical) VTE prevention (medical) IIIIII ADOPT ADOPT 6,5006,500

Stroke prevention in AF (vs. warfarin)Stroke prevention in AF (vs. warfarin) IIIIII ARISTOTLEARISTOTLE 15,00015,000

Stroke prevention in AF (vs. aspirin)Stroke prevention in AF (vs. aspirin) IIIIII AVERROESAVERROES 5,6005,600

VTE treatment VTE treatment IIIIII In Final PlanningIn Final Planning

Acute Coronary Syndrome Acute Coronary Syndrome IIII APPRAISEAPPRAISE--11 1,8001,800

VTE prevention in cancer VTE prevention in cancer IIII ADVOCATE ADVOCATE 160160

Apixaban Clinical Development:Apixaban Clinical Development:Pursuing Multiple Indications SimultaneouslyPursuing Multiple Indications Simultaneously

VTE VTE –– venous thromboembolismvenous thromboembolism














diabetes patients




Execution of BMS Biologics StrategyExecution of BMS Biologics Strategy

AdnexusAdnexus

DomantisDomantis

Therapeutic Therapeutic Area BiologyArea Biology

Ipilimumab(Cancer)

Belatacept(Solid Organ Transplant)

Angiocept(Cancer)

Anti-CD137(Cancer)

Devens Bulk Devens Bulk ManufacturingManufacturing

SyracuseSyracuse

Third Party Third Party ManufacturersManufacturers

ErbituxErbitux(Cancer)(Cancer)

OrenciaOrencia(Rheumatoid (Rheumatoid Arthritis)Arthritis)


Novel fibronectinNovel fibronectin--based protein therapeutics platform based protein therapeutics platform

Distinct from conventional and domain antibodiesDistinct from conventional and domain antibodies

Freedom to operate in existing MAb spaceFreedom to operate in existing MAb space

E. coliE. coli--based production may result in lower costbased production may result in lower costof goodsof goods

Improved Discovery cycle time and associated lower Improved Discovery cycle time and associated lower cost per development candidatecost per development candidate

Ability to bind two targets simultaneouslyAbility to bind two targets simultaneously

AdnexusAdnexus’’ lead product, Angioceptlead product, Angiocept, in Phase II, in Phase II

Adnexus: The OpportunityAdnexus: The Opportunity


AngioceptAngiocept

Potent and specific antagonist of VEGFRPotent and specific antagonist of VEGFR--22

Comparable or better activity than AvastinComparable or better activity than Avastinin animal modelsin animal models

Encouraging clinical profileEncouraging clinical profile–– Generally well toleratedGenerally well tolerated–– Favorable and consistent pharmacokinetic Favorable and consistent pharmacokinetic

profileprofile–– Clinical observations of VEGFRClinical observations of VEGFR--2 blockade 2 blockade –– Stable disease demonstrated in several patients Stable disease demonstrated in several patients

with advanced, refractory malignancieswith advanced, refractory malignancies

Transitioned to Phase IITransitioned to Phase II


2008 Key Data Flow2008 Key Data Flow

OrenciaOrenciaLupus: ACR, Oct 2008Lupus: ACR, Oct 2008Early RA: ACR, Oct 2008Early RA: ACR, Oct 2008RA Prevention: EULAR, June 2008RA Prevention: EULAR, June 2008

SprycelSprycel Solid Tumors: data available 1H 2008Solid Tumors: data available 1H 2008ErbituxErbitux Lung: ASCO, June 2008Lung: ASCO, June 2008

IxempraIxempra MBC MBC --046 survival data: ASCO Breast, Sept 2008046 survival data: ASCO Breast, Sept 2008MBC MBC --048 survival data: SABCS, Dec 2008048 survival data: SABCS, Dec 2008

BelataceptBelatacept Ph III data available: 4Q 2008Ph III data available: 4Q 2008IpilimumabIpilimumab Metastatic melanoma: ASCO, June 2008Metastatic melanoma: ASCO, June 2008

SaxagliptinSaxagliptin Ph III data: ADA, June 2008Ph III data: ADA, June 2008Ph III data: EASD, Sept 2008Ph III data: EASD, Sept 2008

DapagliflozinDapagliflozin Ph IIb data: ADA, June 2008Ph IIb data: ADA, June 2008

PlavixPlavix ACTIVEACTIVE--A data available: 2H 2008A data available: 2H 2008CURRENT data available: 2H 2008CURRENT data available: 2H 2008

ApixabanApixaban Ph II ACS data available: 3Q 2008Ph II ACS data available: 3Q 2008Ph III VTE prevention data: ASH, Dec 2008Ph III VTE prevention data: ASH, Dec 2008

bristol myerd squibb 26th Annual JPMorgan Healthcare Conference

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