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1Not For Promotional Use
ADA 2008 Highlights*ADA 2008 Highlights*
Investor TeleconferenceJune 11, 2008
*American Diabetes AssociationJune 6 – June 10, 2008
*American Diabetes AssociationJune 6 – June 10, 2008
Fred Fiedorek, MDVice President, Global Clinical Research
Fred Fiedorek, MDVice President, Global Clinical Research
Roland Chen, MDGroup Director, Global Clinical Research
Roland Chen, MDGroup Director, Global Clinical Research
2Not For Promotional Use
Comments will be about the CompanyComments will be about the Company’’s future plans and s future plans and prospects that may be forwardprospects that may be forward--looking statements under looking statements under thethe Private Securities Litigation Reform Act of 1995.Private Securities Litigation Reform Act of 1995.We caution that actual results may differ materially from We caution that actual results may differ materially from those indicated by these forwardthose indicated by these forward--looking statements aslooking statements asa result of various important factors, including those a result of various important factors, including those discussed in the Companydiscussed in the Company’’s most recent annual report on s most recent annual report on Form 10Form 10--K, periodic reports on Form 10K, periodic reports on Form 10--Q and current Q and current reports on Form 8reports on Form 8--K. These documents are available from K. These documents are available from the SEC, the Bristolthe SEC, the Bristol--Myers Squibb web site or fromMyers Squibb web site or fromBristolBristol--Myers Squibb Investor Relations. While we may elect Myers Squibb Investor Relations. While we may elect to update forwardto update forward--looking statements at some point in the looking statements at some point in the future, we specifically disclaim any obligation to do so,future, we specifically disclaim any obligation to do so,even if our estimates change. even if our estimates change.
3Not For Promotional Use
Diabetes: A Growing, Global ProblemDiabetes: A Growing, Global Problem
Source: WHOSource: WHO
Type 2 Diabetes prevalence expected to grow Type 2 Diabetes prevalence expected to grow from 190 million to 330 million by 2030from 190 million to 330 million by 20305050--70% of patients are not controlled70% of patients are not controlled
3
Mexico Mexico –– highest highest prevalence rates in prevalence rates in
the world: 12.4%the world: 12.4%India and China will make up India and China will make up
nearly 50% of the total nearly 50% of the total number of patients with number of patients with
diabetes in 2030diabetes in 2030
Europe prevalence is Europe prevalence is lower (~4.6%), but lower (~4.6%), but
increasing, especially in increasing, especially in the southern countriesthe southern countries
Diabetes growing rapidly Diabetes growing rapidly in U.S. in U.S. –– current current
prevalence rate 6.7%prevalence rate 6.7%
NOT FOR PROMOTIONAL USE
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Majority of Patients Are Not Optimally Majority of Patients Are Not Optimally ControlledControlled
Source: Adelphi, 2006 Disease SpecificProgrammes, NHWS 2006
6469
5851
6257
0
20
40
60
80
100Pa
tient
s (%
)60% of
US diabetic patients
do not know their A1c or FPG values
Lack of involvement / motivation / compliance / knowledge leads to progression of disease, with nearly 2/3 of patients not controlled
USUS UKUK FRFR GERGER ITLITL SPNSPN
Percentage of patients not controlled,Percentage of patients not controlled,by market (relative to HbA1c target of 7.0%) by market (relative to HbA1c target of 7.0%)
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The Progressive Nature of Type 2 Diabetes The Progressive Nature of Type 2 Diabetes Ultimately Overwhelms MedicationsUltimately Overwhelms Medications
Glycemic Control in an Illustrative Patient
HbA
1c Goal*A1c=<7Goal*Goal*
A1c=<7A1c=<7
Normal***A1c=5%
Normal***Normal***A1c=5%A1c=5%
Goal**A1c=<6.5
Goal**Goal**A1c=<6.5A1c=<6.5
5yrs
~30 Years~30 Years
Slope =
0.75% per 5
yrs.
Potential Potential treatment treatment changechange
FirstAgent
Sources: ADOPT, UKPDS(*) According to the ADA; (**) according to the AACE/ACE; (***) according to the NIH
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Pharmacologic Intervention in DiabetesPharmacologic Intervention in Diabetes
Several different classes of oral antidiabetic agents are Several different classes of oral antidiabetic agents are availableavailable
Most agents fail after 3Most agents fail after 3--5 years; the current paradigm is 5 years; the current paradigm is one of adding a new treatment to an existing regimenone of adding a new treatment to an existing regimen
Some patients do not even reach the 3Some patients do not even reach the 3--5 year time to fail 5 year time to fail point because of adverse events or poor tolerancepoint because of adverse events or poor tolerance
The market is and continues to be an addThe market is and continues to be an add--on marketon market
New classes have an important place in overall New classes have an important place in overall managementmanagement
There remains a need for new therapiesThere remains a need for new therapies
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Site of Action of Oral Antidiabetic AgentsSite of Action of Oral Antidiabetic Agents
HyperglycemiaHyperglycemia
Increased glucoseIncreased glucoseproductionproduction
Reduced glucose uptake Reduced glucose uptake and utilizationand utilization
Carbohydrate Carbohydrate LoadLoad
Impaired Insulin Secretion
PancreasPancreas
LiverLiver
Skeletal Skeletal MuscleMuscle
MetforminMetforminThiazolidinedionesThiazolidinediones
MetforminMetforminThiazolidinedionesThiazolidinediones
DPPDPP--4 inhibitors4 inhibitors
SulfonylureasSulfonylureasDPPDPP--4 inhibitors4 inhibitors
SGLT2 inhibitorsSGLT2 inhibitors
KidneyKidneyGlucose Glucose reabsorptionreabsorption
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Unmet Medical Needs Still RemainUnmet Medical Needs Still Remain
Optimal glycemic control on treatmentOptimal glycemic control on treatmentSustainable A1c reduction/glycemic Sustainable A1c reduction/glycemic efficacyefficacyConcurrent weight management Concurrent weight management Delaying or halting disease progressionDelaying or halting disease progressionImproving patient complianceImproving patient complianceFinding additional therapies that are Finding additional therapies that are efficacious, well tolerated and safeefficacious, well tolerated and safe
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ADA Highlights: BristolADA Highlights: Bristol--Myers SquibbMyers Squibb
Key data presented for twoKey data presented for two--late stage pipeline late stage pipeline compounds in collaboration with AstraZeneca:compounds in collaboration with AstraZeneca:
Saxagliptin Phase 3 monotherapy study: Saxagliptin Phase 3 monotherapy study: Produced significant reductions in HbA1c, FPG, Produced significant reductions in HbA1c, FPG, PPG PPG
Dapagliflozin Phase 2B study: Reductions in all Dapagliflozin Phase 2B study: Reductions in all measures of glycemic control with addition of measures of glycemic control with addition of weight lossweight loss
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Saxagliptin OverviewSaxagliptin Overview
Highly potent and selective DPPHighly potent and selective DPP--4 inhibitor4 inhibitor
Completed Phase 3 registrational programCompleted Phase 3 registrational program
Well toleratedWell tolerated
Produced significant reductions in all key Produced significant reductions in all key measures of glucose controlmeasures of glucose control
On track for midOn track for mid--year submissionyear submission
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Patient Exposures Throughout Patient Exposures Throughout Saxagliptin ProgramSaxagliptin Program
Phase 1 and 2Phase 1 and 2~110 subjects exposed to saxagliptin at 20~110 subjects exposed to saxagliptin at 20--80x the80x the5 mg dose for up to 6 weeks5 mg dose for up to 6 weeks~670 subjects exposed to saxagliptin at 2~670 subjects exposed to saxagliptin at 2--10x the10x the5 mg dose for up to 12 weeks5 mg dose for up to 12 weeks
Phase 3 Phase 3 ~1000 patients treated at 10 mg dose for up to 2 years~1000 patients treated at 10 mg dose for up to 2 years>3000 patients treated at any dose in Phase 3>3000 patients treated at any dose in Phase 3
Clinical correlates to the skin lesions in monkeys have Clinical correlates to the skin lesions in monkeys have not been identified in human clinical trials of saxagliptinnot been identified in human clinical trials of saxagliptin
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Previously Disclosed Saxagliptin DataPreviously Disclosed Saxagliptin Data
Pharmacokinetics and safetyPharmacokinetics and safety2.5 to 400 mg2.5 to 400 mgNo identified clinically meaningful drug interactionsNo identified clinically meaningful drug interactionsNo dose adjustment required with hepatic impairmentNo dose adjustment required with hepatic impairmentMay be administered without regard to age or genderMay be administered without regard to age or gender
Phase 2 data recently publishedPhase 2 data recently publishedDiabetes Obesity MetabolismDiabetes Obesity Metabolism 2008; 10: 3762008; 10: 376--386386
Phase 3 addPhase 3 add--on to metformin study presented aton to metformin study presented atADA 2007ADA 2007
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Saxagliptin AddSaxagliptin Add--On to Metformin:On to Metformin:Significant HbA1c Reductions From BaselineSignificant HbA1c Reductions From Baseline
**PP values vs placebo + MET: values vs placebo + MET: PP<0.0001<0.0001..Bars indicate 95% twoBars indicate 95% two--sided confidence interval.sided confidence interval.
Adjusted Change From BaselineDifference in Adjusted Change FromBaseline vs Placebo + MET
PBO + MET PBO + MET (N = 175)(N = 175)
SAXA 2.5 mgSAXA 2.5 mg+ MET+ MET
(N = 186)(N = 186)
SAXA 5 mgSAXA 5 mg+ MET + MET
(N = 186)(N = 186)
SAXA 10 mgSAXA 10 mg+ MET+ MET
(N = 180)(N = 180)
%%
*--11* *--0.80.8
--0.60.6
--0.40.4
--0.20.2
00
0.20.2
0.40.4
--0.730.73 --0.720.72--0.830.83
Phase 3 Study Phase 3 Study --014, ADA June 2007014, ADA June 2007
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Saxagliptin Monotherapy Study Design: Saxagliptin Monotherapy Study Design: ADA 2008ADA 2008
N = 401 Treatment-Naïve T2DM
N = 66 Treatment-Naïve T2DM
A1c7.0-10.0% to Enroll
2.5 mg Saxa QD*
A1c10.0-12.0%
PBO*
5 mg Saxa QD*
10 mg Saxa QD*
10 mg Saxa QD*
24 Weeks
*If rescue criteria met in ST, add Metformin 500*If rescue criteria met in ST, add Metformin 500--2000 mg total daily dose, enter LT phase; Metformin rescue also 2000 mg total daily dose, enter LT phase; Metformin rescue also available in LT extension (42 weeks)available in LT extension (42 weeks)
42 Months
Metformin 500 mg QD* (PBO if enter LT via rescue)
2.5 mg Saxa QD*
5 mg Saxa QD*
10 mg Saxa QD*
10 mg Saxa QD*
SuperioritySuperiority
SuperioritySuperiority
SuperioritySuperiority
2 Week
PBO Lead In
Phase 3 Study Phase 3 Study --011, ADA June 2008011, ADA June 2008
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Significant Reductions in HbA1c, FPG, PPGSignificant Reductions in HbA1c, FPG, PPGFrom Baseline at Week 24 From Baseline at Week 24
A1cA1c((%)%)
Fasting Plasma GlucoseFasting Plasma Glucose(mg/dL)(mg/dL)
Postprandial GlucosePostprandial Glucose(mg(mg minmin/dL)/dL)
Saxagliptin + MetSaxagliptin + Met
PBO + MetPBO + Met2.5 mg2.5 mg 5 mg5 mg 10 mg10 mg
-0.43 -0.46-0.54
0.19
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
-14.53
-8.67
-16.75
6.06
-25.0
-20.0
-15.0
-10.0
-5.0
0.0
5.0
10.0
15.0
20.0
-6868 -6896
-8084
-646.6
-12000
-10000
-8000
-6000
-4000
-2000
0
2000
Phase 3 Study Phase 3 Study --011, ADA June 2008011, ADA June 2008
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PBOMain Cohort
N=95
Saxagliptin Main Cohort
N=306
SaxagliptinOpen-Label
Cohort N=66
Total patients with AEs (%) 68 (71.6) 231 (75.5) 40 (60.6)
Upper respiratory tract infection
11 (11.6) 27 (8.8) 6 (9.1)
Headache 7 (7.4) 25 (8.2) 5 (7.6)
Urinary tract infection 4 (4.2) 21 (6.9) 3 (4.5)
Nasopharyngitis 6 (6.3) 18 (5.9) 3 (4.5)
Sinusitis 3 (3.2) 17 (5.6) 1 (1.5)
Most Common (Most Common (≥≥5%) Adverse Events 5%) Adverse Events Reported In The Main CohortReported In The Main Cohort
Phase 3 Study Phase 3 Study --011, ADA June 2008011, ADA June 2008
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Saxagliptin: WhatSaxagliptin: What’’s Next?s Next?
NDA submission by midNDA submission by mid--yearyear
Additional Phase 3 data planned for disclosure Additional Phase 3 data planned for disclosure at EASD in Septemberat EASD in September–– Combination studies with SU, TZDCombination studies with SU, TZD–– Initial combination therapy with metforminInitial combination therapy with metformin
Life cycle program underway Life cycle program underway
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Dapagliflozin OverviewDapagliflozin Overview
First in a new class that inhibits renal glucose First in a new class that inhibits renal glucose reabsorption reabsorption
Stable CStable C--glucoside molecule that allowsglucoside molecule that allowsonceonce--daily dosingdaily dosing
In Phase 3 developmentIn Phase 3 development–– MonotherapyMonotherapy–– CombinationCombination
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Effects of SGLT2 Inhibition on Renal Effects of SGLT2 Inhibition on Renal Glucose ReabsorptionGlucose Reabsorption
Intestine KidneyKidney
UrineUrinePlasmaPlasmaDiet
DapagliflozinDapagliflozin
GlucoseGlucoseSGLT1
SGLT1 SGLT2
Potential benefits of Potential benefits of selectiveselective SGLT2 inhibition:SGLT2 inhibition:InsulinInsulin--independent glucose loweringindependent glucose lowering
Loss of calories in urine, with potential for weight Loss of calories in urine, with potential for weight controlcontrol
GlucoseGlucose
GlucoseGlucose GlucoseGlucose GlucoseGlucose
20Not For Promotional Use
At the ADA, data on dapagliflozin was presented from the At the ADA, data on dapagliflozin was presented from the largest and longest (12 weeks) trial of an SGLT2 Renal largest and longest (12 weeks) trial of an SGLT2 Renal Glucose Reabsorption Inhibitor to date. Results Glucose Reabsorption Inhibitor to date. Results demonstrated that dapagliflozin:demonstrated that dapagliflozin:
Induced controlled glucosuriaInduced controlled glucosuria
Improved glycemic controlImproved glycemic control-- Reduced fasting glucoseReduced fasting glucose-- Reduced postprandial glucoseReduced postprandial glucose-- Reduced HbA1cReduced HbA1c
Lowered weightLowered weight
Showed little propensity to cause hypoglycemiaShowed little propensity to cause hypoglycemia
Demonstrated no clear adverse safety or tolerability signals Demonstrated no clear adverse safety or tolerability signals over 12 weeksover 12 weeks
ADA 2008: Dapagliflozin ADA 2008: Dapagliflozin
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Dapagliflozin Registrational ProgramDapagliflozin Registrational Program
Patient PopulationPatient Population Treatment TypesTreatment TypesTreatmentTreatment--NaNaïïveve Monotherapy vs. Monotherapy vs.
placeboplaceboInitial combination Initial combination with metforminwith metformin
AddAdd--on Therapyon TherapyTreatmentTreatment--Experienced Experienced (previous treatment (previous treatment failure)failure)
Versus placebo:Versus placebo:•• MetforminMetformin•• SulfonylureaSulfonylurea•• TZDTZD•• InsulinInsulin
Active control:Active control:•• SulfonylureaSulfonylurea•• Others under Others under
considerationconsideration
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ADA 2008 Highlights*ADA 2008 Highlights*
Investor TeleconferenceJune 11, 2008
*American Diabetes AssociationJune 6 – June 10, 2008
*American Diabetes AssociationJune 6 – June 10, 2008
Fred Fiedorek, MDVice President, Global Clinical Research
Fred Fiedorek, MDVice President, Global Clinical Research
Roland Chen, MDGroup Director, Global Clinical Research
Roland Chen, MDGroup Director, Global Clinical Research