New Jersey, U.S.A.

Daejeon, Korea

Shanghai, China

Seoul, Korea

YKP3089Novel Neurotherapeutic

ASENTMarch 2009

Martin Brecher, MD

Life ScienceFair Lawn, New Jersey

2

YKP3089 Preclinical Summary

Animal Model Profile

Anticonvulsant Profile Broad spectrum activity in Rat & Mice (i.p., p.o.)

Anxiolytic Profile Active in diverse AX models in Rat & Mice (i.p., p.o.)

Pain Profile Potent efficacy in Chung & Bennett models in Rat

Additional Profile Hypoxia model in Mice

Conditioned Avoidance Rat model

YKP3089

Anticonvulsant Profile

YKP3089

Compounds

(Mice, i.p., ED50 mg/kg)

Electrical

Tonic Generalized Seizures

Chemical

Myoclonic/Generalized Absence Seizures

MES PTZ PIC

YKP3089 9.8 28.5 34.5

Lamotrigine 7.5 >40.0 >40.0

Topiramate 33.0 >800 >500

Phenytoin 6.5 >50 >50

Carbamazepine 9.9 >50 >50

Valproate 287 209 209

Ethosuximide >1000 130 130

3Data Source: NIH

Anticonvulsant Profile

YKP3089

Compounds

(Rat, ip, ED50 mg/kg)

Refractory epilepsy

Partial Complex

Formation/Progression of Epilepsy

Intractable Seizures

KindlingHippocampal

Lithium-pilocarpine intractable seizures

YKP3089 16.4 7.0

Lamotrigine ++ ND

Topiramate - ND

Phenytoin +/- -

Carbamazepine +/- -

Valproate + +

Ethosuximide - ND

4

5

Anticonvulsant Profile

Data Source: NIH

Compounds

(Mice, i.p., ED50 mg/kg)

6 Herz Partial Psychomotor Test

Therapy-Resistant Partial Seizures

22mA 32mA 44mA

YKP3089* 11.0 17.9 16.5

Lamotrigine ND 50% at 20 ND

Phenytoin ND 58% at 40 ND

Carbamazepine ND 75% at 40 & 80 ND

Topiramate ND >300 ND

YKP3089

Anxiolytic Profile

Effective in a wide variety

of anxiety models

Light-Dark Box

Social Interaction

Fear-Potentiated Startle

Marble-Burying

Elevated Plus Maze

Defensive withdrawal, etc.

Active in Rats and Mice

Anxiolytic Test YKP3089 Buspirone

Light-Dark Box(Mice, IP)

+++ +++

Social Interaction(Rat,PO)

+++ ++

Fear-Potentiated Startle

(Rat, IP)

+++ +++

Marble-Burying(Mice, IP)

+++ +++

YKP3089

+++ - ED50 <20mg/kg++ - ED50 <30mg/kg

6

Analgesic (Neuropathic Pain) Profile

Excellent activity in models of neuropathic pain

Improved efficacy compared to gabapentin

Chung Model Bennett Model

YKP3089 Gabapentin YKP3089 Gabapentin

Mechanical allodynia +++ +++ +++ +++

Cold allodynia +++ ++ +++ ++

Heat hyperalgesia +++ ++ +++ +++

YKP3089

+++ - ED50 <50mg/kg++ - ED50 <100mg/kg 7

8

Additional Indication Profile

Model Efficacy Indication

Hypoxia(mice, mg/kg, IP)

√ Neuroprotective

Conditioned Avoidance(rat, mg/kg, IP)

√ Antipsychotic

DOI-Induced Head Twitch(mice, mg/kg, IP)

√ Antipsychotic; Tourette’s

Hippocampal Kindling(mice, mg/kg, IP)

√ Bipolar, Anticonvulsant

Formalin test(mice, mg/kg, IP)

√ Inflammatory pain

YKP3089

9

ADME Excellent PK parameters

Rat PO

Monkey PO

Good metabolic stability

Moderate plasma protein binding

Good Tissue Distribution

Preclinical ADME/Safety/Toxicity

Safety/Toxicity Good Safety

hERG Channel

Monkey CV Telemetry

Respiratory

Gastric

Negative Gene Toxicity

Typical CNS clinical signs

Low teratogenicity potential

YKP3089

10

YKP3089 Clinical Summary

Phase Ia and Ib Clinical Trials (USA) No clinically significant changes in both single and multiple dose study

ECG Vital signs Hematology Serum chemistry Urinalysis

YKP3089 shows dose-response relation of clinical signs and adverse events

Excellent PK Parameters Data suggest once-per-day dosing

YKP3089 is well-tolerated Adverse events were mild and CNS related

YKP3089

11Time, hr

0 20 40 60 80 100 120 140 160

0.01

0.1

1

10

Phase 1a Clinical Study, MDS AA22780Mean Plasma Concentration Time Profiles of YKP3089 Following Single Oral Doses

To Male Health Subjects at 5 mg (n=6), 10 mg (n=7), 25 mg (n=7), 50 mg (n=6), 100 mg (n=6)200 mg (n=7), 300 mg (n=7), 400 mg (n=7), 500 mg (n=7), 600 mg (n=7), and 750 mg (n=7)

Time, hr

0 20 40 60 80 100 120 140 160

YK

P30

89 C

onc.

in P

lasm

a,

g/m

L

0

5

10

15

20

5 mg10 mg25 mg50 mg100 mg200 mg300 mg400 mg500 mg 600 mg 750 mg

YKP3089 Single Dose PK

12

Both Cmax and AUC linearly correlated with dose Steady State occurred by Day 12

YKP3089 Multiple Dose PK

13

Mean Plasma Concentration - Time Profile Comparison of YKP3089Following A Single Oral Dose of 300 mg to Normal Subjects (n = 15)

Food effect Study, Fed verses Fasting Treatment (AA39450)

Time, hr

0 20 40 60 80 100 120 140 160 180

YK

P30

89 M

ean

Pla

sm

a C

on

c.,

g/m

L

0

2

4

6

8

10

Fed Fast

Time, hr

0 20 40 60 80 100 120 140 160 180

Fed Fast

YKP3089 Food Effect Study PK

14

YKP3089 Highlights

Phase I Clinical Trials in USAPhase I Clinical Trials in USA Favorable PK profile Once a day dosing potential Low adverse effects

Phase I Clinical Trials in USAPhase I Clinical Trials in USA Favorable PK profile Once a day dosing potential Low adverse effects

Safety & ToxicitySafety & Toxicity High safety margin Low QTc prolongation potential Low teratogenic potential

Safety & ToxicitySafety & Toxicity High safety margin Low QTc prolongation potential Low teratogenic potential

EfficacyEfficacy Potential versatile CNS drug: Epilepsy, Anxiety, Neuropathic Pain, Bipolar

Disorder, Dementia, Schizophrenia, etc. Broad spectrum: Epilepsy Possible novel mechanism

EfficacyEfficacy Potential versatile CNS drug: Epilepsy, Anxiety, Neuropathic Pain, Bipolar

Disorder, Dementia, Schizophrenia, etc. Broad spectrum: Epilepsy Possible novel mechanism

YKP3089