Neuroscience and Pain
Transcript of Neuroscience and Pain
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GDS_0311727_Sulivan_v7 1
Neuroscience and PainNeuroscience and PainJames Sullivan, Ph.D.Divisional Vice PresidentNeuroscience Discovery
Abbott Laboratories
James Sullivan, Ph.D.Divisional Vice PresidentNeuroscience Discovery
Abbott Laboratories
GDS_0311727 Sullivan_v7 2
Expanding Leadership in Neuroscience and PainExpanding Leadership in Neuroscience and Pain
! World�s largest pharma market �growing at ~10 percent annually
� Pain: $20 billion� Neurological/psychiatric: $44 billion
! Large unmet need and scientific opportunity! Strong commercial foundation and established leadership! Billion dollar opportunities for pain in community market! Developing breakthrough science in pain and neurology
! World�s largest pharma market �growing at ~10 percent annually
� Pain: $20 billion� Neurological/psychiatric: $44 billion
! Large unmet need and scientific opportunity! Strong commercial foundation and established leadership! Billion dollar opportunities for pain in community market! Developing breakthrough science in pain and neurology
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Established LeadershipEstablished Leadership
! Major marketed products: $1.5 billion in sales� Depakote: #1 treatment for bipolar
and #1 branded treatment for epilepsy� Recognized brands in pain management
(Vicodin, Dilaudid, Mobic)
! Resources to develop breakthrough science� 350 scientists� Centers of Excellence (Ludwigshafen, Abbott Park)
! Strategic collaborations augment internal programs� NeuroSearch, Icagen, Myriad
! Major marketed products: $1.5 billion in sales� Depakote: #1 treatment for bipolar
and #1 branded treatment for epilepsy� Recognized brands in pain management
(Vicodin, Dilaudid, Mobic)
! Resources to develop breakthrough science� 350 scientists� Centers of Excellence (Ludwigshafen, Abbott Park)
! Strategic collaborations augment internal programs� NeuroSearch, Icagen, Myriad
STRONG FOUNDATION IN PAIN AND NEUROSCIENCE STRONG FOUNDATION IN PAIN AND NEUROSCIENCE
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GeneticsGenetics
DopamineDopamineNNRsNNRsH3H3
P2XP2X
VR1VR1
SchizophreniaSchizophreniaSchizophrenia
DepressionDepressionDepressionPainPainPain
Cognitive DisordersCognitive Cognitive DisordersDisorders
Abbott�s Leading-Edge R&D Strategy in Pain and NeuroscienceAbbott�s Leading-Edge R&D Strategy in Pain and NeuroscienceLEVERAGING INNOVATIVE TECHNOLOGY PLATFORMS AND EXISTING BRAND EQUITYLEVERAGING INNOVATIVE TECHNOLOGY PLATFORMS LEVERAGING INNOVATIVE TECHNOLOGY PLATFORMS AND EXISTING BRAND EQUITYAND EXISTING BRAND EQUITY
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Biaxin XLDepakote ERHUMIRAKaletraMeridiaOmnicefTriCorZemplarAbbokinaseChirocaineMavikPrecedexSynagisTarka
HUMIRAJRAPsAAnkylosing spondylitis
Atrasentan Prostate cancer
Dilaudid CR Pain
ABT-773Infections
r-UKBlood clots
Zemplar oralHyper-parathyroidism
SimdaxHeart failure
ClivarineDVT
SegardSepsis
Febuxostat (TMX-67)Gout
Asoprisnil (J867) Fibroids
Lupron 6 month DepotProstate Cancer
HUMIRACrohn�s diseasePsoriasis
ABT-874 (J695)Autoimmune disease
AtrasentanKidney cancerOvarian cancerBrain cancerLung cancer
ABT-510Cancer
ABT-751Cancer
Vicodin CRPain
ABT-089Cognition
Iron oligosaccarideIron deficiency
ABT-724ED
ABT-224Constipation
Asoprisnil (J867) Endometriosis
J956HRT
ABT-325 (IL-18)Autoimmune disease
ABT-828 Cancer
ABT-202Pain
ABT-894Pain
ABT-834Cognition
ABT-239Cognition
ABT-578Restenosis
ABT-670ED
COT kinaseSignal transduction
inhibitor Cytokine inhibitorCo-stimulation inhibitorChemotaxis inhibitorCell adhesion inhibitorMulti kinase inhibitorAngiogenesis inhibitorAKT inhibitorBcl-2/Bcl-xL inhibitorChk1 inhibitorMC4 agonistPARP inhibitorABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 agonistReplication inhibitorNovel PIAnti-diabetes Weight regulatorNext generation PPILG122941
>70 other compounds
Phase IVPhase IIIPhase IIPhase IAdvanced Preclinical
Neuroscience/Pain PipelineNeuroscience/Pain Pipeline
ABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 Agonist
ABTABT--769769VR1VR1Na channelNa channelD3 antagonistD3 antagonistH3 antagonistH3 antagonistNNRNNR5HT55HT5P2XP2XD4 AgonistD4 Agonist
ABT-202Pain
ABT-894Pain
ABT-834Cognition
ABT-239Cognition
ABTABT--202202PainPain
ABTABT--894894PainPain
ABTABT--834834CognitionCognition
ABTABT--239239CognitionCognition
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Biaxin XLDepakote ERHUMIRAKaletraMeridiaOmnicefTriCorZemplarAbbokinaseChirocaineMavikPrecedexSynagisTarka
HUMIRAJRAPsAAnkylosing spondylitis
Atrasentan Prostate cancer
Dilaudid CR Pain
ABT-773Infections
r-UKBlood clots
Zemplar oralHyper-parathyroidism
SimdaxHeart failure
ClivarineDVT
SegardSepsis
Febuxostat (TMX-67)Gout
Asoprisnil (J867) Fibroids
Lupron 6 month DepotProstate Cancer
HUMIRACrohn�s diseasePsoriasis
ABT-874 (J695)Autoimmune disease
AtrasentanKidney cancerOvarian cancerBrain cancerLung cancer
ABT-510Cancer
ABT-751Cancer
Vicodin CRPain
ABT-089Cognition
Iron oligosaccarideIron deficiency
ABT-724ED
ABT-224Constipation
Asoprisnil (J867) Endometriosis
J956HRT
ABT-325 (IL-18)Autoimmune disease
ABT-828 Cancer
ABT-202Pain
ABT-894Pain
ABT-834Cognition
ABT-239Cognition
ABT-578Restenosis
ABT-670ED
COT kinaseSignal transduction
inhibitor Cytokine inhibitorCo-stimulation inhibitorChemotaxis inhibitorCell adhesion inhibitorMulti kinase inhibitorAngiogenesis inhibitorAKT inhibitorBcl-2/Bcl-xL inhibitorChk1 inhibitorMC4 agonistPARP inhibitorABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 agonistReplication inhibitorNovel PIAnti-diabetes Weight regulatorNext generation PPILG122941
>70 other compounds
Phase IVPhase IIIPhase IIPhase IAdvanced Preclinical
Neuroscience/Pain PipelineNeuroscience/Pain Pipeline
ABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 Agonist
ABTABT--769769VR1VR1Na channelNa channelD3 antagonistD3 antagonistH3 antagonistH3 antagonistNNRNNR5HT55HT5P2XP2XD4 AgonistD4 Agonist
ABT-202Pain
ABT-894Pain
ABT-834Cognition
ABT-239Cognition
ABTABT--202202PainPain
ABTABT--894894PainPain
ABTABT--834834CognitionCognition
ABTABT--239239CognitionCognition
Vicodin-CRPain
ABT-089Cognition
VicodinVicodin--CRCRPain Pain
ABTABT--089089CognitionCognition
Dilaudid-CR Pain
DilaudidDilaudid--CR CR PainPain
Depakote-ERDepakoteDepakote--ERER
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Biaxin XLDepakote ERHUMIRAKaletraMeridiaOmnicefTriCorZemplarAbbokinaseChirocaineMavikPrecedexSynagisTarka
HUMIRAJRAPsAAnkylosing spondylitis
Atrasentan Prostate cancer
Dilaudid CR Pain
ABT-773Infections
r-UKBlood clots
Zemplar oralHyper-parathyroidism
SimdaxHeart failure
ClivarineDVT
SegardSepsis
Febuxostat (TMX-67)Gout
Asoprisnil (J867) Fibroids
Lupron 6 month DepotProstate Cancer
HUMIRACrohn�s diseasePsoriasis
ABT-874 (J695)Autoimmune disease
AtrasentanKidney cancerOvarian cancerBrain cancerLung cancer
ABT-510Cancer
ABT-751Cancer
Vicodin CRPain
ABT-089Cognition
Iron oligosaccarideIron deficiency
ABT-724ED
ABT-224Constipation
Asoprisnil (J867) Endometriosis
J956HRT
ABT-325 (IL-18)Autoimmune disease
ABT-828 Cancer
ABT-202Pain
ABT-894Pain
ABT-834Cognition
ABT-239Cognition
ABT-578Restenosis
ABT-670ED
COT kinaseSignal transduction
inhibitor Cytokine inhibitorCo-stimulation inhibitorChemotaxis inhibitorCell adhesion inhibitorMulti kinase inhibitorAngiogenesis inhibitorAKT inhibitorBcl-2/Bcl-xL inhibitorChk1 inhibitorMC4 agonistPARP inhibitorABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 agonistReplication inhibitorNovel PIAnti-diabetes Weight regulatorNext generation PPILG122941
>70 other compounds
Phase IVPhase IIIPhase IIPhase IAdvanced Preclinical
Neuroscience/Pain Pipeline � Today�s FocusNeuroscience/Pain Pipeline � Today�s Focus
ABT-202 Pain
ABT-894Pain
ABT-834 Cognition
ABT-239Cognition
ABTABT--202 202 PainPain
ABTABT--894894PainPain
ABTABT--834 834 CognitionCognition
ABTABT--239239CognitionCognition
Vicodin-CR Pain
ABT-089 Cognition
VicodinVicodin--CR CR PainPain
ABTABT--089 089 CognitionCognition
ABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 Agonist
ABTABT--769769VR1VR1Na channelNa channelD3 antagonistD3 antagonistH3 antagonistH3 antagonistNNRNNR5HT55HT5P2XP2XD4 AgonistD4 Agonist
Dilaudid-CR Pain
DilaudidDilaudid--CR CR PainPain
Depakote-ERDepakoteDepakote--ERER
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The Pain MarketThe Pain Market
! $20 billion market worldwide �~10 percent annual growth
! Vast, underserved patient population ! Need for more efficacious
and better-tolerated drugs� No breakthrough classes
of pain drugs in 30 years� Rapid advances in understanding
of pain pathways have generated new molecular targets
! $20 billion market worldwide �~10 percent annual growth
! Vast, underserved patient population ! Need for more efficacious
and better-tolerated drugs� No breakthrough classes
of pain drugs in 30 years� Rapid advances in understanding
of pain pathways have generated new molecular targets
PAIN � #1 REASON PATIENTS SEEK PHYSICIAN CAREPAIN PAIN �� #1 REASON PATIENTS SEEK PHYSICIAN CARE#1 REASON PATIENTS SEEK PHYSICIAN CARE
May 19, 2003May 19, 2003
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PainPain
! Inflammatory/nociceptive pain! Neuropathic pain! Inflammatory/nociceptive pain! Neuropathic pain
TWO MAJOR PAIN STATESTWO MAJOR PAIN STATESTWO MAJOR PAIN STATES
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PainPain
! Inflammatory/nociceptive pain� Acute � Post-op pain, bone fractures� Chronic � OA, RA, back pain, cancer pain
! Neuropathic pain
! Inflammatory/nociceptive pain� Acute � Post-op pain, bone fractures� Chronic � OA, RA, back pain, cancer pain
! Neuropathic pain
TWO MAJOR PAIN STATESTWO MAJOR PAIN STATESTWO MAJOR PAIN STATES
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Inflammatory/Nociceptive Pain StatesInflammatory/Nociceptive Pain States
Pain
Sev
erity
Pain
Sev
erity
GenericOpioids
COXCOX��2s2sGenericNSAIDs
OpioidsOpioids
OTCs
Pain DurationPain Duration
MODERATE TO SEVERE PAIN � 187 MILLION PRESCRIPTIONS ($5.5B);GENERIC PRESCRIPTIONS MASK TRUE POTENTIAL OF THE MARKETMODERATE TO SEVERE PAIN � 187 MILLION PRESCRIPTIONS ($5.5B);GENERIC PRESCRIPTIONS MASK TRUE POTENTIAL OF THE MARKET
SevereSevere
Mild Mild
ModerateModerate
AcuteAcute ChronicChronic
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GenericOpioids
COXCOX��2s2sGenericNSAIDs
OpioidsOpioids
OTCs
Unmet Needs:
Inflammatory/Nociceptive Pain StatesInflammatory/Nociceptive Pain States
! Dosing convenience! Safety/tolerability! Sustained efficacy
SevereSevere
Mild Mild
ModerateModerate
Pain
Sev
erity
Pain
Sev
erity
AcuteAcute ChronicChronicPain DurationPain Duration
MODERATE TO SEVERE PAIN � 187 MILLION PRESCRIPTIONS ($5.5B);GENERIC PRESCRIPTIONS MASK TRUE POTENTIAL OF THE MARKETMODERATE TO SEVERE PAIN � 187 MILLION PRESCRIPTIONS ($5.5B);GENERIC PRESCRIPTIONS MASK TRUE POTENTIAL OF THE MARKET
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ABBOTT COMPOUNDS ADDRESS KEY AREAS OF UNMET NEEDABBOTT COMPOUNDS ADDRESS KEY AREAS OF UNMET NEEDABBOTT COMPOUNDS ADDRESS KEY AREAS OF UNMET NEED
Vicodin-CR
ABT-202
Dilaudid-CR
Inflammatory/Nociceptive Pain StatesInflammatory/Nociceptive Pain States
Pain
Sev
erity
Pain
Sev
erity
Pain DurationPain Duration
SevereSevere
Mild Mild
ModerateModerate
AcuteAcute ChronicChronic
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Near-Term Opportunity:Dilaudid-CR for Chronic PainNear-Term Opportunity:Dilaudid-CR for Chronic Pain
! Addresses key unmet need of dosing convenience
! In late Phase III development
! Projected filing in 2004! Peak-year potential
of >$500 million in community market
! Addresses key unmet need of dosing convenience
! In late Phase III development
! Projected filing in 2004! Peak-year potential
of >$500 million in community market
PATIENT-FRIENDLY, ONCE-DAILY VERSION OF A WIDELY RECOGNIZED BRAND PATIENT-FRIENDLY, ONCE-DAILY VERSION OF A WIDELY RECOGNIZED BRAND
0
0.5
1
1.5
2
2.5
3
72 78 84 90 96
PK Profile of Dilaudid-CR vs. DilaudidPK Profile of Dilaudid-CR vs. DilaudidDilaudid-CR � 16 mg q24hDilaudid � 4 mg q6h
Time (hours)
Blo
od L
evel
s (n
g/m
L)
8
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Near-Term Opportunity:Vicodin-CR for Acute PainNear-Term Opportunity:Vicodin-CR for Acute Pain
! 8 � 12 hour dosing (vs. 3 � 4 hour dosing with current version)
! Rapid and sustained analgesia for acute pain
! Currently in Phase II! Projected filing in 2005! Peak-year potential
of >$500 million in community market
! 8 � 12 hour dosing (vs. 3 � 4 hour dosing with current version)
! Rapid and sustained analgesia for acute pain
! Currently in Phase II! Projected filing in 2005! Peak-year potential
of >$500 million in community market
0 4 8 12
0
10
20
30
40
Time (hours)
Vicodin-CRVicodin
PK Profile of Vicodin-CR vs. VicodinPK Profile of Vicodin-CR vs. Vicodin
MORE CONVENIENT DOSING OF A WIDELY RECOGNIZED BRAND MORE CONVENIENT DOSING OF A WIDELY RECOGNIZED BRAND
Blo
od L
evel
s (n
g/m
L)
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Neuronal Nicotinic Acetylcholine Receptor (NNR)Neuronal Nicotinic Acetylcholine Receptor (NNR)
! Abbott is the first company to establish efficacy of NNRs in:� Pain � ADHD � AD
! Abbott is the first company to establish efficacy of NNRs in:� Pain � ADHD � AD
Mild Cognitive ImpairmentMild Cognitive Mild Cognitive ImpairmentImpairment
SchizophreniaSchizophreniaSchizophrenia Neuropathic Pain Neuropathic Pain Neuropathic Pain NNRNNR
ADHDADHDADHD
Inflammatory PainInflammatory PainInflammatory Pain
BREAKTHROUGH TECHNOLOGY PLATFORM FOR PAIN / NEUROSCIENCEBREAKTHROUGH TECHNOLOGY PLATFORM FOR PAIN / NEUROSCIENCE
Alzheimer�s Disease (AD)Alzheimer�s Disease (AD)Alzheimer�s Disease (AD)
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Neuronal Nicotinic Acetylcholine Receptor (NNR)Neuronal Nicotinic Acetylcholine Receptor (NNR)
! Abbott is the first company to establish efficacy of NNRs in:� Pain � ADHD � AD
! Abbott is the first company to establish efficacy of NNRs in:� Pain � ADHD � AD
Alzheimer�s Disease (AD)Alzheimer�s Disease (AD)Alzheimer�s Disease (AD)
Mild Cognitive ImpairmentMild Cognitive Mild Cognitive ImpairmentImpairment
SchizophreniaSchizophreniaSchizophrenia NNRNNR
ADHDADHDADHD
BREAKTHROUGH TECHNOLOGY PLATFORM FOR PAIN / NEUROSCIENCEBREAKTHROUGH TECHNOLOGY PLATFORM FOR PAIN / NEUROSCIENCE
Inflammatory PainInflammatory Pain
Neuropathic Pain Neuropathic Pain Neuropathic Pain
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ABT-202: NNR for Chronic Inflammatory/Nociceptive PainABT-202: NNR for Chronic Inflammatory/Nociceptive Pain
! Superior efficacy vs. COX-2/NSAIDs! Efficacy comparable to opioids in inflammatory pain models! Tolerability very favorable vs. opioids
! Superior efficacy vs. COX-2/NSAIDs! Efficacy comparable to opioids in inflammatory pain models! Tolerability very favorable vs. opioids
PreclinicalPreclinical Efficacy Efficacy �� Inflammatory/Inflammatory/NociceptiveNociceptive PainPain
>75%>75%>75%>75%OpioidsOpioids
<30%<30%>75%>75%COXCOX--22>75%>75%>75%>75%ABTABT--202202
ModerateModerate--SevereSevereMildMild--ModerateModerate
EARLY-STAGE DEVELOPMENTEARLYEARLY--STAGE DEVELOPMENTSTAGE DEVELOPMENT
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PainPain
! Inflammatory/nociceptive pain! Neuropathic pain � encompasses
a wide range of pain syndromes� Diabetic neuropathy� Cancer neuropathy� HIV pain� Postherpetic neuralgia
! Inflammatory/nociceptive pain! Neuropathic pain � encompasses
a wide range of pain syndromes� Diabetic neuropathy� Cancer neuropathy� HIV pain� Postherpetic neuralgia
TWO MAJOR PAIN STATESTWO MAJOR PAIN STATESTWO MAJOR PAIN STATES
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Neuropathic PainNeuropathic Pain
! 10 million patients worldwide! Current market leaders only offer
modest efficacy! Key needs:
� Greater efficacy� Faster onset of action
! 10 million patients worldwide! Current market leaders only offer
modest efficacy! Key needs:
� Greater efficacy� Faster onset of action
Unmet Need
EfficacyEfficacy
Chronic Neuropathic
Chronic Neuropathic
100%100%
50%50%
0%0%
Gabapentin(Neurontin)
TCAs
SSRIs
GROWING MARKET WITH SIGNIFICANT UNMET MEDICAL NEEDSGROWING MARKET WITH SIGNIFICANT UNMET MEDICAL NEEDSGROWING MARKET WITH SIGNIFICANT UNMET MEDICAL NEEDS
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Neuropathic PainNeuropathic Pain
! 10 million patients worldwide! Current market leaders only offer
modest efficacy! Key needs:
� Greater efficacy� Faster onset of action
! 10 million patients worldwide! Current market leaders only offer
modest efficacy! Key needs:
� Greater efficacy� Faster onset of action
EfficacyEfficacy
Chronic Neuropathic
Chronic Neuropathic
ABBOTT COMPOUNDS ADDRESS UNMET NEEDSABBOTT COMPOUNDS ADDRESS UNMET NEEDSABBOTT COMPOUNDS ADDRESS UNMET NEEDS
100%100%
50%50%
0%0%
Gabapentin(Neurontin)
TCAs
SSRIs
NNRs
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ABT-594: First-Generation NNRABT-594: First-Generation NNR
! Efficacy comparable to market leader in neuropathic pain
! Limited tolerability� Key Issue: nausea
and GI side effects
! Discovery goal: Identify compound with 30-fold improvement intherapeutic index
! Efficacy comparable to market leader in neuropathic pain
! Limited tolerability� Key Issue: nausea
and GI side effects
! Discovery goal: Identify compound with 30-fold improvement intherapeutic index
Efficacy in Neuropathic Pain PatientsEfficacy in Neuropathic Pain Patients
PlaceboABT-594 150 µgABT-594 225 µgABT-594 300 µg
0 1 2 3 4 5 6 7
Incr
easi
ng P
ain
Rel
ief
Week
*
**
**
** *****
****
**
**
**
**
*
* p < 0.05 ** p < 0.01
EFFICACY IN MULTIPLE CLINICAL MODELSEFFICACY IN MULTIPLE CLINICAL MODELSEFFICACY IN MULTIPLE CLINICAL MODELS
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ABT-594: First-Generation NNRABT-594: First-Generation NNR
! Efficacy comparable to market leader in neuropathic pain
! Limited tolerability� Key Issue: nausea
and GI side effects
! Discovery goal: Identify compound with 30-fold improvement intherapeutic index
! Next-generation compound: ABT-894
! Efficacy comparable to market leader in neuropathic pain
! Limited tolerability� Key Issue: nausea
and GI side effects
! Discovery goal: Identify compound with 30-fold improvement intherapeutic index
! Next-generation compound: ABT-894
EFFICACY IN MULTIPLE CLINICAL MODELSEFFICACY IN MULTIPLE CLINICAL MODELSEFFICACY IN MULTIPLE CLINICAL MODELS
ABT-894
EfficacyEfficacy
Low High
High
Toler
abilit
yTo
lerab
ility
ABT-594
30-Fold TolerabilityImprovement
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ABT-894: Next-Generation NNRABT-894: Next-Generation NNR
! Full efficacy in multiple preclinical models of neuropathic pain! Full efficacy in multiple preclinical models of neuropathic pain
PreclinicalPreclinical Efficacy Efficacy �� NeuropathicNeuropathic PainPain
50%50%>75%>75%GabapentinGabapentin(Neurontin)
<30%<30%<30%<30%COXCOX--22>75%>75%>75%>75%ABTABT--894894
ChemotherapyChemotherapySciatic Nerve InjurySciatic Nerve Injury
EARLY-STAGE DEVELOPMENT FOR NEUROPATHIC PAINEARLY-STAGE DEVELOPMENT FOR NEUROPATHIC PAIN
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ABT-894: Next-Generation NNRABT-894: Next-Generation NNR
! Exhibits marked improvement vs. ABT-594 in models of neuropathic pain
! Exhibits marked improvement vs. ABT-594 in models of neuropathic pain
0
25
50
75
100
1 10
GI side effectsEfficacy
% o
f Max
imal
Pos
sibl
e R
espo
nse
Plasma Conc. (ng/mL)
0
25
50
75
100
10 100 1,000
Efficacy
% o
f Max
imal
Pos
sibl
e R
espo
nse
Plasma Conc. (ng/mL)
ABT-894ABT-594
GI side effects
FULL EFFICACY WITHOUT GI SIDE EFFECTSFULL EFFICACY WITHOUT GI SIDE EFFECTS
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Abbott Is Poised to Expand Its Presence in PainAbbott Is Poised to Expand Its Presence in Pain
! Today� Widely recognized brand names in pain (Vicodin, Dilaudid, Mobic)
! Future� Potential for combined sales of >$1 billion in community market
! Dilaudid-CR: projected 2004 filing ! Vicodin-CR: projected 2005 filing
� Long-term potential to revolutionize pain treatment! 2008 � 2010: ABT-202 and ABT-894
! Today� Widely recognized brand names in pain (Vicodin, Dilaudid, Mobic)
! Future� Potential for combined sales of >$1 billion in community market
! Dilaudid-CR: projected 2004 filing ! Vicodin-CR: projected 2005 filing
� Long-term potential to revolutionize pain treatment! 2008 � 2010: ABT-202 and ABT-894
SIGNIFICANT NEAR-TERM AND LONG-TERM OPPORTUNITYSIGNIFICANT NEARSIGNIFICANT NEAR--TERM AND LONGTERM AND LONG--TERM OPPORTUNITYTERM OPPORTUNITY
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Abbott�s Leading-Edge R&D Strategy in NeuroscienceAbbott�s Leading-Edge R&D Strategy in NeuroscienceLEVERAGING INNOVATIVE TECHNOLOGY PLATFORMS AND EXISTING BRAND EQUITYLEVERAGING INNOVATIVE TECHNOLOGY PLATFORMS LEVERAGING INNOVATIVE TECHNOLOGY PLATFORMS AND EXISTING BRAND EQUITYAND EXISTING BRAND EQUITY
GeneticsGenetics
DopamineDopamineNNRsNNRsH3H3
P2XP2X
VR1VR1
SchizophreniaSchizophreniaSchizophrenia
DepressionDepressionDepressionPainPainPain
Cognitive DisordersCognitive Disorders
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Cognitive DisordersCognitive Disorders
! ADHD, mild cognitive impairment, schizophrenia, and Alzheimer�s disease affect greater than 35 million worldwide
! Current therapies� Weak efficacy
in Alzheimer�s disease� No treatments available
for cognitive aspects of schizophrenia
� Stimulants used to treat ADHD
! ADHD, mild cognitive impairment, schizophrenia, and Alzheimer�s disease affect greater than 35 million worldwide
! Current therapies� Weak efficacy
in Alzheimer�s disease� No treatments available
for cognitive aspects of schizophrenia
� Stimulants used to treat ADHD
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Biaxin XLDepakote ERHUMIRAKaletraMeridiaOmnicefTriCorZemplarAbbokinaseChirocaineMavikPrecedexSynagisTarka
HUMIRAJRAPsAAnkylosing spondylitis
Atrasentan Prostate cancer
Dilaudid CR Pain
ABT-773Infections
r-UKBlood clots
Zemplar oralHyper-parathyroidism
SimdaxHeart failure
ClivarineDVT
SegardSepsis
Febuxostat (TMX-67)Gout
Asoprisnil (J867) Fibroids
Lupron 6 month DepotProstate Cancer
HUMIRACrohn�s diseasePsoriasis
ABT-874 (J695)Autoimmune disease
AtrasentanKidney cancerOvarian cancerBrain cancerLung cancer
ABT-510Cancer
ABT-751Cancer
Vicodin CRPain
ABT-089Cognition
Iron oligosaccarideIron deficiency
ABT-724ED
ABT-224Constipation
Asoprisnil (J867) Endometriosis
J956HRT
ABT-325 (IL-18)Autoimmune disease
ABT-828 Cancer
ABT-202Pain
ABT-894Pain
ABT-834Cognition
ABT-239Cognition
ABT-578Restenosis
ABT-670ED
COT kinaseSignal transduction
inhibitor Cytokine inhibitorCo-stimulation inhibitorChemotaxis inhibitorCell adhesion inhibitorMulti kinase inhibitorAngiogenesis inhibitorAKT inhibitorBcl-2/Bcl-xL inhibitorChk1 inhibitorMC4 agonistPARP inhibitorABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 agonistReplication inhibitorNovel PIAnti-diabetes Weight regulatorNext generation PPILG122941
>70 other compounds
Phase IVPhase IIIPhase IIPhase IAdvanced Preclinical
Neuroscience Pipeline � Today�s FocusNeuroscience Pipeline � Today�s Focus
ABT-769VR1Na channelD3 antagonistH3 antagonistNNR5HT5P2XD4 Agonist
ABTABT--769769VR1VR1Na channelNa channelD3 antagonistD3 antagonistH3 antagonistH3 antagonistNNRNNR5HT55HT5P2XP2XD4 AgonistD4 Agonist
ABT-202Pain
ABT-894Pain
ABT-834 Cognition
ABT-239Cognition
ABTABT--202202PainPain
ABTABT--894894PainPain
ABTABT--834 834 CognitionCognition
ABTABT--239239CognitionCognition
Vicodin-CRPain
ABT-089 Cognition
VicodinVicodin--CRCRPain Pain
ABTABT--089 089 CognitionCognition
Dilaudid-CR Pain
DilaudidDilaudid--CR CR PainPain
Depakote-ERDepakoteDepakote--ERER
GDS_0311727 Sullivan_v7 30
ABT-089: NNR for Cognitive DisordersABT-089: NNR for Cognitive Disorders
! Preclinical profile suggests utility in cognitive deficits in ADHD, AD and schizophrenia
! Preclinical profile suggests utility in cognitive deficits in ADHD, AD and schizophrenia
Efficacy in Preclinical Model of Attention/DistractibilityEfficacy in Preclinical Model of Attention/Distractibility
Impr
oved
Per
form
ance
Impr
oved
Per
form
ance
40
50
60
70
80
90
100
Placebo 4 8 16 33 66 Placebo 185 464 927 1855Dose (nmol/kg, i.m.)
% C
orre
ct R
espo
nses
Chance
* * * *
*
ABT-089 Methylphenidate (Ritalin)
STRONG EFFICACY WITHOUT STIMULANT-LIKE SIDE EFFECTSSTRONG EFFICACY WITHOUT STIMULANT-LIKE SIDE EFFECTS
16
GDS_0311727 Sullivan_v7 31
! Excellent safety profile in preclinical models� >100-fold separation between efficacy and GI side effects
! Excellent safety profile in preclinical models� >100-fold separation between efficacy and GI side effects
Blood (ng/mL)Blood (ng/Blood (ng/mLmL))
11 1010 100100 1,0001,000 10,00010,000
Blood levels where efficacy occurs
Blood levels where efficacy occurs Blood levels where
GI side effects startBlood levels where GI side effects start
ABT-089: NNR for Cognitive DisordersABT-089: NNR for Cognitive Disorders
GDS_0311727 Sullivan_v7 32
ABT-089: Next-Generation NNR ABT-089: Next-Generation NNR
! Phase I completed� Efficacy signal � Very well-tolerated
! Phase II underway� Efficacy studies
! AD! ADHD! Schizophrenia
! Phase I completed� Efficacy signal � Very well-tolerated
! Phase II underway� Efficacy studies
! AD! ADHD! Schizophrenia
Simple Reaction Time
-20
-10
0
10
20
30
40
0 mg 5 mg 10 mg 20 mg 30 mg 40 mg
Dosing Groups
Decr
ease
in R
eact
ion
Tim
e (m
s)
Improvement in Measure of Attention in Humans
Improvement in Measure of Attention in Humans
PHASE I DATA SUPPORTS PRECLINICAL PROFILEPHASE I DATA SUPPORTS PRECLINICAL PROFILE
17
GDS_0311727 Sullivan_v7 33
Histamine H3 ReceptorsHistamine H3 Receptors
H3 AntagonistH3 Antagonist
H3H3
HistamineHistamine
ACh Receptor
Learning AttentionLearning Attention
AChACh
Acetylcholine (ACh) is important for learningand attention
Acetylcholine (ACh) is important for learningand attention
Brain SynapseBrain Synapse
H3 AntagonistH3 Antagonist
HistamineHistamineH3H3
Vigilance AlertnessVigilance Alertness
H1Histamine modulates vigilance and alertnessHistamine modulates vigilance and alertness
NEW MOLECULAR APPROACH TO ATTENTIONAL/COGNITIVE DISORDERSNEW MOLECULAR APPROACH TO ATTENTIONAL/COGNITIVE DISORDERSNEW MOLECULAR APPROACH TO ATTENTIONAL/COGNITIVE DISORDERS
GDS_0311727 Sullivan_v7 34
Novel H3 Receptor Antagonists IdentifiedNovel H3 Receptor Antagonists Identified
! Designed by molecular modeling (structural biology)
! Potent and selective antagonists identified
! Lead compounds active in preclinical models of attention/cognition
! Designed by molecular modeling (structural biology)
! Potent and selective antagonists identified
! Lead compounds active in preclinical models of attention/cognition
Interaction of Abbott Compound Interaction of Abbott Compound With Human HWith Human H33 ReceptorsReceptors
18
GDS_0311727 Sullivan_v7 35
! Potent and selective H3 antagonist
! Efficacy in attention/cognition models
! Excellent safety and tolerability
� No stimulant liability unlike stimulants
! Very favorable PK� No drug-drug interactions
unlike atomoxetine (Strattera)
! Potent and selective H3 antagonist
! Efficacy in attention/cognition models
! Excellent safety and tolerability
� No stimulant liability unlike stimulants
! Very favorable PK� No drug-drug interactions
unlike atomoxetine (Strattera)
H3 Antagonists for Cognitive DisordersH3 Antagonists for Cognitive Disorders
Rodent Model of Attention/ImpulsivityRodent Model of Attention/Impulsivity
-200
-100
0
100
200
300
Impr
ovem
ent o
ver c
ontr
ol (s
ec.)
0.01 0.03 0.1 0.3Veh
Treatment (mg/kg, s.c.)
ABT-834Methylphenidate
(Ritalin)
1
ABT-834 � EARLY CLINICAL DEVELOPMENTABTABT--834 834 �� EARLY CLINICAL DEVELOPMENTEARLY CLINICAL DEVELOPMENT
GDS_0311727 Sullivan_v7 36
Expanding Leadership in Neuroscience and PainExpanding Leadership in Neuroscience and Pain
! World�s largest pharma market �growing at ~10 percent annually
� Pain: $20 billion� Neurological/psychiatric: $44 billion
! Large unmet need and scientific opportunity! Strong commercial foundation and established leadership! Billion dollar opportunities for pain in community market! Developing breakthrough science in pain and neurology
! World�s largest pharma market �growing at ~10 percent annually
� Pain: $20 billion� Neurological/psychiatric: $44 billion
! Large unmet need and scientific opportunity! Strong commercial foundation and established leadership! Billion dollar opportunities for pain in community market! Developing breakthrough science in pain and neurology
19
GDS_0311727_Sulivan_v7 37
Neuroscience and PainNeuroscience and PainJames Sullivan, Ph.D.Divisional Vice PresidentNeuroscience Discovery
Abbott Laboratories
James Sullivan, Ph.D.Divisional Vice PresidentNeuroscience Discovery
Abbott Laboratories