International Research for Global Health

NAEJA Pharmaceutical Inc.

INTEGRATED MEDICINAL CHEMISTRY

Drug discovery Contract Research Organization (CRO)

Previously SynPhar

Privately owned

63,000 ft2 facility

Based in Edmonton, Canada

Core ExpertisePre-Clinical Development

HIT

Validation

Lead

Identification

Lead

Optimization

Target

Validation

IND &

Clinical Trials

Track Record

Success Stories: Anti-infectives

Tazobactam• Design, Synthesis, & Screening of -Lactamase Inhibitor• 4 Year Program• Collaboration with Taiho Pharmaceuticals• Marketed by Wyeth

N

S

O

OO

CO2H

H

NN

N

SYNPHAR TAIHOHIT

Validation

IND &

Clinical TrialsLead

Identification

Lead

Optimization

HIT

Validation

Lead

Identification

Lead

Optimization

IND &

Clinical Trials

Success Stories: Inflammation

Mofezolac

(DisopainTM)• Design & Synthesis of NSAID• 4 Year Program• Collaboration with Taiho Pharmaceuticals• Marketed by Mitsubishi Pharmaceuticals

SYNPHAR TAIHO

NO

CO2HMeO

MeO

Europe

US

Japan

NAEJA Track Record Past 5 Years*

*(% revenue)

Large

PharmaBiotech

Longest collaboration

12 yearsLongest contract

4 years

New market

2008

Multiple projects & clients

Proven IP security

Single Client – Multiple ProgramsAnti-infectives & inflammation

NAEJA

Hit Generation

and ValidationHit to Lead Lead

Optimization

Can

did

ate

CLIENT Phase 2

Phase 2b

Phase 1: 2009

On hold: biological liability

Candidate selection: 2009

Lead declaration

{One program

2007 2008 2009

Project starts: Q1Hit structure: narrow activity spectrum

Racemic

Limited SAR

Undeveloped chemistry: unusual scaffold

No crystal structure

Project starts: Q1Hit structure: narrow activity spectrum

Racemic

Limited SAR

Undeveloped chemistry: unusual scaffold

No crystal structure

Q3: Crystal structure

Q3: Crystal structure

Q1: ½ Kg

pre-candidate synthesized

Q1: ½ Kg

pre-candidate synthesized

Candidate declaration

>98% purity

>98% eefffff

Candidate declaration

>98% purity

>98% eefffff

Q4: Racemic

lead #1 declared

Q4: Racemic

lead #1 declared

Q1: Validated

thigh model

Q1: Validated

thigh modelQ3: Pre-candidate

#1 put on hold:

biological liability

Q3: Pre-candidate

#1 put on hold:

biological liability

Q1: Chemistry development, SAR, MIC panelQ1: Chemistry development, SAR, MIC panel

Q1: Process developmentQ1: Process development

Q2: chiral HPLCQ2: chiral HPLC

Q1: ADMEQ1: ADMEQ1: Racemic

lead #2 declared

Q1: Racemic lead #2 declared

Q3: Molecular modeling & SBDDQ3: Molecular modeling & SBDD

CASE STUDYAnti-infective Program

= NAEJA

= CLIENT

Successful Recent Programs

NAEJA

Hit Generation

and ValidationHit to Lead Lead

Optimization

Can

did

ate

Phase 1b/2: Cardiovascular disease

Clinical trials: anti-fungal

Alzheimer's program

Anti-viral program

Clinical trials: Pain management

Clinical trials: anti-bacterial

Other

Antifungal

Antibacterial

CVD

Cancer Antiviral

CNS

Inflammation

Medicinal Chemistry Projects

Papers 42

Patents 19

Papers 15

Patents 4Papers 2

Patents 5

Papers 20

Patents 5

Papers 5

Patents 1

Papers 3

Papers 4

Patents 10

Papers 4

Patents 9

Services

Chemistry Services

Full FTE: medicinal, synthetic, and process chemists.

Medicinal chemistry programs: hit to candidate including

process development (22 L).

Custom synthesis.

Chemical Information Support

SciFinder™, Reaxys™, ACS journals online, NERAC, & CISTI.

NAEJA FTE’s Director100% PhDs

Project

Coordinator100% PhDs

Scientist90% PhDs

Canada

US

Europe

Asia

Japan

Staffing Chemistry: 71% Biology: 7%Analytical: 5% Admin: 17%

PhDs & Postdocs by Training Location

Locations of Ph.D.’s and Postdocs

Computational Chemistry Services

Hit Discovery: ligand docking

Sybyl™, Glide/ pharmacophore generationSchrödinger™

Lead Optimization: ligand docking

Sybyl™, Glide/ QSARSchrödinger™

Physical Properties: pKa, log P, log D, & solubilityACD™ software

Analytical Support: HPLC

Separation & Purification

WATERS™ Autopurification System

WATERS™ PREP HPLC: routine scale: 100-500 mg

WATERS™ LC Module Plus: semi-prep NP/chiral; 50-100 mg

Analysis

WATERS™ 600 Series

Chiral analysis (CHIRALPAK™-AD, AD-RH, OD, OD-R, OF, OB, OJ)

LC-MS

WATERS™- Micromass ZQ LC/MS (EI & APcI)

WATERS™- Acquity LC/MS (Sample Manager; PDA Detector & SQ Mass Detector)

MIC Determination: NCCLS standard procedures & ATCC reference strain

- Bacterial panels include Gram-positive, Gram-negative, and anerobes

- Fungal panels include yeast and filamentous fungi

Cross-resistance studies

- Panels of strains expressing drug resistance mechanisms

De novo resistance development studies

Kill time studies

Microbiology – in vitro studies

Post-antimicrobial effect (PAE) studies

Effect of body milieus on activity

Determination of activity on recently collected clinical isolates

- Collection of over 4000 bacterial and fungal clinical isolates

High-throughput screening of activity

- Beckman™ 2000 automated workstation

Drug-drug interaction studies

Microbiology – in vitro studies

Bioavailability/Pharmacokinetics: in vitro testing parameters

Aqueous solubility

Partition coefficient (log D, n-octanol/PBS, pH 7.4)

Plasma protein binding (ultrafiltration)

A-B Permeability (MDCK)

Metabolic stability (human liver microsomes, hepatocytes)

UPLC-MS-MS Screen

Drug Safety and Development: in vitro testing parameters

Cytochrome P450 inhibition

Cytochrome P450 induction

Animal Facilities (CCAC)*

Capacity: Conventional housing Level II biohazard 200 mice/40 rats - PK 200 mice/24 rats – efficacy

Preclinical PK: in vivo metabolism, preliminary acute & sub acute toxicology

Bioavailablity studies (including preformulation using cosolvents)

Blood/plasma concentrations (AUC, t½, Cmax, CL, & Vd)

Tissue concentration/distribution

In vivo metabolite profiling

Acute & sub acute toxicological evaluation in rodents

*CCAC – Canadian Council of Animal Care

The NAEJA Package

Included in the price of an FTE:

Consumables

Patent/literature searches (SciFinder™, Reaxys™, NERAC)

Waste disposal (overseen by safety committee, SOP’s in place)

IP 100% owned by the client (confidentiality SOP in place)

NAEJA Summary

Experience

22 year track record in drug discovery.

Collaborations with over 125 pharmaceutical companies.

Delivered candidates in a number of therapeutic areas.

Expertise

90% of our research scientists are PhDs.

Services

Pre-clinical discovery

Custom services to full range medicinal chemistry programs.

Contact Information

Dr Sameeh Salama Dr Chris Diaper Senior Director AssociateBusiness & Development Business & Development

NAEJA Pharmaceutical Inc.4290-91A Street, Edmonton, Alberta, Canada. T6E 5V2

Tel: (780) 462-4044; Fax: (780) 461-0196

E-mail: info@naeja.com

www.naeja.com