Neuroscience and Pain

1

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




2


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


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

3


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--834834CognitionCognition






Dilaudid CR Pain

ABT-773Infections

r-UKBlood clots


SimdaxHeart failure

ClivarineDVT

SegardSepsis







ABT-510Cancer

ABT-751Cancer

Vicodin CRPain

ABT-089Cognition


ABT-724ED

ABT-224Constipation


J956HRT


ABT-828 Cancer

ABT-202Pain

ABT-894Pain

ABT-834Cognition

ABT-239Cognition

ABT-578Restenosis

ABT-670ED



>70 other compounds


Neuroscience/Pain PipelineNeuroscience/Pain Pipeline



ABT-202Pain

ABT-894Pain

ABT-834Cognition

ABT-239Cognition





Vicodin-CRPain

ABT-089Cognition

VicodinVicodin--CRCRPain Pain


Dilaudid-CR Pain

DilaudidDilaudid--CR CR PainPain

Depakote-ERDepakoteDepakote--ERER

4





Dilaudid CR Pain

ABT-773Infections

r-UKBlood clots


SimdaxHeart failure

ClivarineDVT

SegardSepsis







ABT-510Cancer

ABT-751Cancer

Vicodin CRPain

ABT-089Cognition


ABT-724ED

ABT-224Constipation


J956HRT


ABT-828 Cancer

ABT-202Pain

ABT-894Pain

ABT-834Cognition

ABT-239Cognition

ABT-578Restenosis

ABT-670ED



>70 other compounds


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--834 834 CognitionCognition


Vicodin-CR Pain

ABT-089 Cognition

VicodinVicodin--CR CR PainPain




Dilaudid-CR Pain




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

5


PainPain

! Inflammatory/nociceptive pain! Neuropathic pain! Inflammatory/nociceptive pain! Neuropathic pain

TWO MAJOR PAIN STATESTWO MAJOR PAIN STATESTWO MAJOR PAIN STATES


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


6


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


GenericOpioids

COXCOX��2s2sGenericNSAIDs

OpioidsOpioids

OTCs

Unmet Needs:


! 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

7


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


Pain

Sev

erity

Pain

Sev

erity

Pain DurationPain Duration

SevereSevere

Mild Mild

ModerateModerate

AcuteAcute ChronicChronic


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


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


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


! 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


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)


Neuronal Nicotinic Acetylcholine Receptor (NNR)Neuronal Nicotinic Acetylcholine Receptor (NNR)

! 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)

9


Neuronal Nicotinic Acetylcholine Receptor (NNR)Neuronal Nicotinic Acetylcholine Receptor (NNR)



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


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

10


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



Neuropathic PainNeuropathic Pain

! 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

11


Neuropathic PainNeuropathic Pain







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


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



and GI side effects


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

12


ABT-594: First-Generation NNRABT-594: First-Generation NNR



and GI side effects


! Next-generation compound: ABT-894



and GI side effects


! 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


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

13


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


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

14


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


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

15





Dilaudid CR Pain

ABT-773Infections

r-UKBlood clots


SimdaxHeart failure

ClivarineDVT

SegardSepsis







ABT-510Cancer

ABT-751Cancer

Vicodin CRPain

ABT-089Cognition


ABT-724ED

ABT-224Constipation


J956HRT


ABT-828 Cancer

ABT-202Pain

ABT-894Pain

ABT-834Cognition

ABT-239Cognition

ABT-578Restenosis

ABT-670ED



>70 other compounds


Neuroscience Pipeline � Today�s FocusNeuroscience Pipeline � Today�s Focus



ABT-202Pain

ABT-894Pain

ABT-834 Cognition

ABT-239Cognition





Vicodin-CRPain

ABT-089 Cognition

VicodinVicodin--CRCRPain Pain


Dilaudid-CR Pain




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


! 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


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


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


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


! 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


Expanding Leadership in Neuroscience and PainExpanding Leadership in Neuroscience and Pain







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

Documents

Neuroscience and Pain