2. NAEJA Pharmaceutical Inc.
North America, Europe, Japan, Asia
Drug discovery Contract Research Organization (CRO)
Previously SynPhar (1987‐1999)
Privately owned
63,000 ft2 facility
Based in Edmonton, Canada

3. NAEJA Pharmaceutical Inc.
Client Base (2008‐2009)*
Biotech Large
Pharma
Japan
US
Longest collaboration
Europe
12 years
Longest contract
4 years *(% revenue)

4. NAEJA’s Role in – Infrastructure
Drug Discovery – Expertise
– Experience
Design Synthesis
HIT CANDIDATE
Analysis Test

5. Computational
Chemistry Infrastructure:
Molecular modeling/QSAR
Survey chemical space
Target libraries: defined
physical properties
Design Synthesis
Analysis Test

6. Computational Chemistry
• Hit Discovery:
– ligand docking
– pharmacophore generation
• Lead Optimization:
– ligand docking
– QSAR
• Physical Properties:
– pKa, log P, log D, & solubility

7. Medicinal Chemistry Infrastructure:
Review TPP
Review SAR
Experience in design:
ADME/DMPK/toxicity
Design Synthesis
Analysis Test

8. Staffing Chemistry: 71%
Director Biology: 7%
100% PhDs Analytical: 5%
Admin: 17%
Project PhDs & Postdocs by Training Location
Coordinator
100% PhDs
Canada
US
Europe
Scientist Asia
90% PhDs Japan

9. PhDs & Postdoc Training of NAEJA Scientists

10. Synthetic Chemistry
Infrastructure: Over 60 Ph.D. Chemists
Reactions up to 22L scale
Access to SciFinder, Reaxys
Access to NMR, MS, LC‐MS,
analytical and prep HPLC
Design Synthesis
Analysis Test

11. Analytical & Purification Support
Purification Analytical
– Prep HPLC – Chiral HPLC
– Automated prep LC‐MS – CHIRALPAK™ AD, AD‐RH, OD, OD‐R,
– Routine scale 100‐500 mg OF, OB, OJ
– Semi‐prep NP/chiral – LC‐MS
– Routine scale 50‐100 mg
– Elemental analysis, IR, & optical
– Biotage rotations
– Routine NP/RP
– Specialty columns also available 1H NMR
e.g. alumina, cyano, ion‐exchange –
– 2 × 400 MHz

12. Infrastructure:
Design Synthesis
Biological Services
Analysis Test Microbiology
DMPK
Pharmacology
Toxicity

13. Select Organism Microbiology
Select Organism Microbiology
– Time‐kill studies
– Time‐kill studies
– Post antibiotic effect (PAE) studies
– Post antibiotic effect (PAE) studies
Microbiology, DMPK
– Frequency of resistance
– Frequency of resistance
Rodent in vivo Efficacy
Rodent in vivo Efficacy & Toxicity
–
Superficial skin infection
–
Superficial skin infection
–
Pneumonia
–
Pneumonia
Primary MIC Panel
Primary MIC Panel –
Septicemia
–
Septicemia
– NCCL procedures
– NCCL procedures –
Sepsis
In vitro PK
In vitro PK
–
Sepsis
– Gram +ve and –ve
– Gram +ve and –ve –
Thigh infection
–
Thigh infection
– Physicochemical
– Physicochemical In vitro Toxicity
In vitro Toxicity
– Anaerobes properties
properties – hERG
– Anaerobes – hERG
– Fungi
– Fungi Secondary Panel
Secondary Panel – Chemical & metabolic
– Chemical & metabolic – CYP 450 panel
– CYP 450 panel
Stability
Stability
– MIC90’s
– MIC90’s In vivo Safety and PK
In vivo Safety and PK
– > 4000 clinical isolates
– > 4000 clinical isolates – Acute/sub acute dosing
– Acute/sub acute dosing
– Includes 2009 strains
– Includes 2009 strains – Cmax, Tmax, Vdd, t½, AUC, %F
– Cmax, Tmax, V , t½, AUC, %F
Hit Candidate

14. In vivo Pharmacology Models
Septicemia Pneumonia
– Staphylococcus aureus MRSA – Streptococcus pneumoniae
– Staphylococcus Aureus MSSA
– Aspergillus fumigatus
– Candida albicans
– Aspergillus fumigatus Sepsis
Thigh infections
– Staphylococcus aureus MRSA
– Staphylococcus aureus MRSA – Staphylococcus aureus MSSA
– Staphylococcus aureus MSSA
– Escherichia coli
– Streptococcus pneumoniae
– Escherichia coli Superficial skin infection
Animal Facilities (CCAC): Level II biohazard – Staphylococcus aureus MSSA

15. Pharmacokinetics
in vitro in vivo
– Aqueous solubility – Bioavailability studies
– Partition coefficients – Blood/plasma concentrations
– Plasma protein binding – Tissue concentration/distribution
– A‐B permeability (MDCK) – Metabolite profiling
– Metabolic stability (microsomes,
hepatocytes)
– UPLC‐MS‐MS screening Animal facilities adhere to CCAC

16. Infrastructure:
Design Synthesis
Scientific Support
Internal: Directors
Minimum industrial Analysis Test
experience – 15 years
External: Consultants
Specific TAs/disciplines

17. NAEJA’s Role in – Infrastructure
Drug Discovery – Expertise
– Experience
Design Synthesis
HIT CANDIDATE
Analysis Test

18. Anti‐infectives:
Tazobactam Track Record:
β‐Lactamase Inhibitor
Collaboration with Taiho
Marketed by Wyeth/Pfizer
Design Synthesis
Analysis Test

19. Anti‐infectives:
SYN‐2190 Track Record:
Licensed:
Anti‐infective Diagnostics
WO 2009/051838
Design Synthesis
Analysis Test

20. Mofezolac (Disopain™) Track Record:
Commercial NSAID
Collaboration with Taiho
Marketed by Mitsubishi
Design Synthesis
Analysis Test

21. Published TAs:
Track Record: Anti‐Infectives:
Topoisomerases
DNA gyrase
β‐Lactamases
Histidine kinase
PPB3, PDK, LeuRS
Design Synthesis Efflux pump inhibitors
Analysis Test

22. Cardiovascular Targets:
Track Record: Antihypertensives ‐ Renin
Anticoagulants ‐ Factor Xa
Cancer:
Cyclin‐dependant kinase Cdk4
Design Synthesis Dermatology:
Androgen receptors
CNS:
NRI’s and 5‐HT1A
Inflammation:
Analysis Test TNF‐α, IL‐23, & PDE4

23. Track Record:
Design Synthesis
Recent Publications:
MIC screening
Bioorg. Med. Chem. Lett.
Analysis Test 2009, 19, 1292, 3374, & 4626
ICAAC 2009 Poster:
Efficacy study:
MRSA mouse skin
infection model

24. Track Record:
Design Synthesis
Scientific Support
Internal: Sr. Directors
Medicinal Chemistry
Analysis Test
Dr Rajeshwar Singh
52 papers; 46 patents
Dr S. N. Maiti
58 papers, 15 patents

25. Papers and Patents
238 in total
Track Record:
Antiinfectives Design Synthesis
Antifungals
CV
Cancer
Inflammation
Mental Health
COPD Analysis Test
Auto Immune
Synthesis
Analytical

26. Track Record:
Design Synthesis
External Consultants
Dr John Domagala
Senior Consultant with IDSC
Previous position: Analysis Test
Executive Director at Pfizer
Prof. Mike James FRS
University of Alberta
Crystallography & Modeling

27. NAEJA’s Role in – Infrastructure
– Expertise
Drug Discovery
– Experience
Design Synthesis
HIT CANDIDATE
Analysis Test

28. Single Client – Concurrent Anti‐infectives
& Inflammation Programs
Candidate
Hit Generation Hit to Lead Lead
and Validation Optimization
NAEJA CLIENT Phase 2
Phase 3
One program
{ On hold: biological liability
Phase 1: 2009
Candidate selection: 2009
Lead declaration: 2009

29. Other Successful Recent Programs
Candidate
Hit Generation Hit to Lead Lead
and Validation Optimization
NAEJA Phase 1b/2: Cardiovascular disease
Clinical trials: Pain management
Clinical trials: anti‐bacterial
Clinical trials: anti‐fungal
Alzheimer's program
Anti‐viral program

30. Project starts: Q1
Project starts: Q1 Q1: Validated
Q1: Validated
thigh model
Q3: Pre‐candidate
Q3: Pre‐candidate
#1 put on hold:
CASE STUDY
Hit structure: narrow activity spectrum
Hit structure: narrow activity spectrum thigh model #1 put on hold:
Racemic
Racemic biological liability
biological liability Anti‐infective Program
Limited SAR
Limited SAR Q1: ½ Kg
= NAEJA
Q1: ½ Kg
Undeveloped chemistry: unusual scaffold
Undeveloped chemistry: unusual scaffold pre‐candidate
pre‐candidate = CLIENT
No crystal structure
No crystal structure synthesized
synthesized
Q1: Chemistry development, SAR, MIC panel
Q1: Chemistry development, SAR, MIC panel
Q1 to Q4 2009
Q1 to Q4 2009 Q4: Racemic
Q4: Racemic Q1: Process development
Q1: Process development
Biochemistry
Biochemistry lead #1 declared
lead #1 declared Candidate declaration
Candidate declaration
>98% purity
>98% purity
Q3: Molecular modeling & SBDD
Q3: Molecular modeling & SBDD Q2: chiral HPLC
Q2: chiral HPLC >98% eefffff
>98% eefffff
Q3: Crystal
Q3: Crystal Q1: Racemic lead
Q1: Racemic lead
structure
structure #2 declared
#2 declared Q1: ADME
Q1: ADME
2007 2008 2009

31. NAEJA Business Models
Compound based Program based
fee‐for‐service Drug discovery
Custom Synthesis FTE R&D Service
Discovery Biology

32. NAEJA Packages:
Compound based
fee‐for‐service Design Synthesis
– Short term
– Fixed deliverables Analysis Test
– All materials & labor included
– Literature searches included
– Client owns 100% of the IP

33. Program Research:
FTE based R&D Service
– Staffing
– 1 computational chemist
– 5 synthetic/medicinal chemists
– 1‐2 biologists Design Synthesis
– Time frame
– 6‐12 months lead generation
– 1‐2 years lead optimization
– Client owns 100% of the IP Analysis Test
– Included in FTE price
– Consumables
– Literature/patent searching
– Waste disposal

34. Contact Information
Dr. Sameeh Salama
Senior Director,
Business Development
Dr. Chris Diaper
Business Development
Associate
NAEJA Pharmaceutical Inc.
4290‐91A Street, Edmonton
Alberta, Canada.
T6E 5V2
Tel: (780) 462‐4044
Fax: (780) 461‐0196
E‐mail: info@naeja.com