More Related Content Similar to NAEJA Presentation (20) NAEJA Presentation2. NAEJA Pharmaceutical Inc.
North America, Europe, Japan, Asia
Drug discovery Contract Research Organization (CRO)
Previously SynPhar (1987â1999)
Privately owned
63,000Â ft2 facility
Based in Edmonton, Canada
3. NAEJA Pharmaceutical Inc.
Client Base (2008â2009)*
Biotech LargeÂ
Pharma
Japan
US
Longest collaboration
Europe
12Â years
Longest contract
4Â years *(%Â revenue)
4. NAEJAâs Role in â Infrastructure
Drug Discovery â Expertise
â Experience
Design Synthesis
HIT CANDIDATE
Analysis Test
5. ComputationalÂ
Chemistry Infrastructure:
Molecular modeling/QSAR
Survey chemical space
Target libraries: definedÂ
physical properties
Design Synthesis
Analysis Test
6. Computational Chemistry
⢠Hit Discovery:
â ligand docking
â pharmacophore generation
⢠Lead Optimization:Â
â ligand docking
â QSAR
⢠Physical Properties:Â
â pKa, log P, log D, & solubility
7. Medicinal Chemistry Infrastructure:
Review TPP
Review SAR
Experience in design:
ADME/DMPK/toxicityÂ
Design Synthesis
Analysis Test
8. Staffing Chemistry:Â 71%Â
Director Biology:Â 7%
100%Â PhDs Analytical:Â 5%Â
Admin:Â 17%
Project PhDs & Postdocs by Training Location
Coordinator
100%Â PhDs
Canada
US
Europe
Scientist Asia
90%Â PhDs Japan
10. Synthetic Chemistry
Infrastructure: Over 60 Ph.D. Chemists
Reactions up to 22L scale
Access to SciFinder, Reaxys
Access to NMR, MS, LCâMS,Â
analytical and prep HPLC
Design Synthesis
Analysis Test
11. Analytical & Purification Support
Purification Analytical
â Prep HPLC â Chiral HPLC
â Automated prep LCâMS â CHIRALPAK⢠AD, ADâRH, OD, ODâR,Â
â Routine scale 100â500 mg OF, OB, OJ
â Semiâprep NP/chiral â LCâMS
â Routine scale 50â100 mg
â Elemental analysis, IR, & opticalÂ
â Biotage rotations
â Routine NP/RP
â Specialty columns also available 1H NMR
e.g. alumina, cyano, ionâexchange â
â 2Â Ă 400Â MHz
12. Infrastructure:
Design Synthesis
Biological Services
Analysis Test Microbiology
DMPK
Pharmacology
Toxicity
13. Select Organism Microbiology
Select Organism Microbiology
â Timeâkill studies
â Timeâkill studies
â Post antibiotic effect (PAE) studies
â Post antibiotic effect (PAE) studies
Microbiology, DMPK
â Frequency of resistance
â Frequency of resistance
Rodent in vivo Efficacy
Rodent in vivo Efficacy & Toxicity
â
Superficial skin infection
â
Superficial skin infection
â
Pneumonia
â
Pneumonia
Primary MIC Panel
Primary MIC Panel â
Septicemia
â
Septicemia
â NCCLÂ procedures
â NCCLÂ procedures â
Sepsis
In vitro PK
In vitro PK
â
Sepsis
â Gram +ve and âve
â Gram +ve and âve â
Thigh infection
â
Thigh infection
â PhysicochemicalÂ
â Physicochemical In vitro Toxicity
In vitro Toxicity
â Anaerobes properties
properties â hERG
â Anaerobes â hERG
â Fungi
â Fungi Secondary Panel
Secondary Panel â Chemical & metabolicÂ
â Chemical & metabolic â CYP 450 panel
â CYPÂ 450Â panel
Stability
Stability
â MIC90âs
â MIC90âs In vivo Safety and PK
In vivo Safety and PK
â > 4000 clinical isolates
â > 4000 clinical isolates â Acute/sub acute dosing
â Acute/sub acute dosing
â Includes 2009 strains
â Includes 2009 strains â Cmax, Tmax, Vdd, t½, AUC, %F
â Cmax, Tmax, V , t½, AUC, %F
Hit Candidate
14. In vivo Pharmacology Models
Septicemia Pneumonia
â Staphylococcus aureus MRSA â Streptococcus pneumoniae
â Staphylococcus Aureus MSSA
â Aspergillus fumigatus
â Candida albicans
â Aspergillus fumigatus Sepsis
Thigh infections
â Staphylococcus aureus MRSA
â Staphylococcus aureus MRSA â Staphylococcus aureus MSSA
â Staphylococcus aureus MSSA
â Escherichia coli
â Streptococcus pneumoniae
â Escherichia coli Superficial skin infection
Animal Facilities (CCAC):  Level II biohazard â Staphylococcus aureus MSSA
15. Pharmacokinetics
in vitro in vivo
â Aqueous solubility â Bioavailability studies
â Partition coefficients â Blood/plasma concentrations
â Plasma protein binding â Tissue concentration/distribution
â AâB permeability (MDCK) â Metabolite profiling
â Metabolic stability (microsomes,Â
hepatocytes)
â UPLCâMSâMS screening Animal facilities adhere to CCAC
16. Infrastructure:
Design Synthesis
Scientific Support
Internal: Directors
Minimum industrial Analysis Test
experience â 15 years
External: ConsultantsÂ
Specific TAs/disciplines
17. NAEJAâs Role in â Infrastructure
Drug Discovery â Expertise
â Experience
Design Synthesis
HIT CANDIDATE
Analysis Test
18. Antiâinfectives:
Tazobactam Track Record:
βâLactamase Inhibitor
Collaboration with Taiho
Marketed by Wyeth/Pfizer
Design Synthesis
Analysis Test
19. Antiâinfectives:
SYNâ2190 Track Record:
Licensed:Â
Antiâinfective Diagnostics
WOÂ 2009/051838
Design Synthesis
Analysis Test
20. Mofezolac (Disopainâ˘) Track Record:
Commercial NSAID
Collaboration with Taiho
Marketed by Mitsubishi
Design Synthesis
Analysis Test
21. Published TAs:
Track Record: AntiâInfectives:
Topoisomerases
DNAÂ gyrase
βâLactamases
Histidine kinase
PPB3, PDK, LeuRS
Design Synthesis Efflux pump inhibitors
Analysis Test
22. Cardiovascular Targets:
Track Record: Antihypertensives â Renin
Anticoagulants â Factor Xa
Cancer:
Cyclinâdependant kinase Cdk4
Design Synthesis Dermatology:
Androgen receptors
CNS:
NRIâs and 5âHT1AÂ
Inflammation:
Analysis Test TNFâÎą, ILâ23, & PDE4
23. Track Record:
Design Synthesis
Recent Publications:
MICÂ screening
Bioorg. Med. Chem. Lett.
Analysis Test 2009, 19, 1292, 3374, & 4626
ICAACÂ 2009Â Poster:
Efficacy study:Â
MRSA mouse skinÂ
infection model
24. Track Record:
Design Synthesis
Scientific Support
Internal: Sr. Directors
Medicinal Chemistry
Analysis Test
Dr Rajeshwar Singh
52Â papers;Â 46Â 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 IDSCÂ
Previous position: Analysis Test
Executive Director at Pfizer
Prof. Mike James FRS
University of Alberta
Crystallography & Modeling
27. NAEJAâs Role in â Infrastructure
â Expertise
Drug Discovery
â Experience
Design Synthesis
HIT CANDIDATE
Analysis Test
28. Single Client â Concurrent Antiâinfectives
& Inflammation Programs
Candidate
Hit Generation Hit to Lead LeadÂ
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 LeadÂ
and Validation Optimization
NAEJA Phase 1b/2: Cardiovascular disease
Clinical trials: Pain management
Clinical trials: antiâbacterial
Clinical trials: antiâfungal
Alzheimer's program
Antiâviral program
30. Project starts: Q1
Project starts: Q1 Q1: Validated
Q1:Â Validated
thigh model
Q3:Â PreâcandidateÂ
Q3:Â PreâcandidateÂ
#1 put on hold:Â
CASEÂ STUDY
Hit structure: narrow activity spectrum
Hit structure: narrow activity spectrum thigh model #1 put on hold:Â
Racemic
Racemic biological liability
biological liability Antiâinfective Program
Limited SAR
Limited SAR Q1: ½ Kg
=Â NAEJA
Q1: ½ Kg
Undeveloped chemistry: unusual scaffold
Undeveloped chemistry: unusual scaffold preâcandidateÂ
preâcandidate = 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%Â purity
>98%Â purity
Q3: Molecular modeling & SBDD
Q3: Molecular modeling & SBDD Q2: chiral HPLC
Q2: chiral HPLC >98% eefffff
>98%Â eefffff
Q3:Â CrystalÂ
Q3: Crystal Q1: Racemic leadÂ
Q1: Racemic leadÂ
structure
structure #2Â declared
#2Â declared Q1:Â ADME
Q1:Â ADME
2007 2008 2009
33. Program Research:
FTE based R&D Service
â Staffing
â 1 computational chemist
â 5 synthetic/medicinal chemists
â 1â2Â biologists Design Synthesis
â Time frame
â 6â12 months lead generation
â 1â2 years lead optimization
â Client owns 100% of the IP Analysis Test
â Included in FTE price
â Consumables
â Literature/patent searching
â Waste disposal