Transcript NAEJA Pharmaceutical Inc. INTEGRATED MEDICINAL CHEMISTRY International Research for Global Health  Drug discovery Contract Research Organization (CRO)  Previously SynPhar  Privately owned  63,000

NAEJA Pharmaceutical Inc.
INTEGRATED MEDICINAL CHEMISTRY
International Research for Global Health
 Drug discovery Contract Research Organization (CRO)
 Previously SynPhar
 Privately owned
 63,000 ft2 facility
 Based in Edmonton, Canada
Core Expertise
Pre-Clinical Development
Target
Validation
HIT
Validation
Lead
Identification
Lead
Optimization
IND &
Clinical Trials
Track Record
Success Stories: Anti-infectives
SYNPHAR
HIT
Validation
TAIHO
Lead
Identification
Lead
Optimization
IND &
Clinical Trials
H O O
S
N
N
O
N
N
CO2H
Tazobactam
• Design, Synthesis, & Screening of -Lactamase Inhibitor
• 4 Year Program
• Collaboration with Taiho Pharmaceuticals
• Marketed by Wyeth
Success Stories: Inflammation
SYNPHAR
HIT
Validation
TAIHO
Lead
Identification
Lead
Optimization
MeO
CO2H
IND &
Clinical Trials
O
N
MeO
• Design & Synthesis of NSAID
• 4 Year Program
• Collaboration with Taiho Pharmaceuticals
• Marketed by Mitsubishi Pharmaceuticals
Mofezolac
(DisopainTM)
NAEJA Track Record
Past 5 Years*
Biotech
Japan
New market
2008
Europe
Longest contract
4 years
*(% revenue)
Large
Pharma
US
Longest collaboration
12 years
Multiple projects & clients
Proven IP security
Single Client – Multiple Programs
Hit Generation
and Validation
NAEJA
Hit to Lead
Lead
Optimization
Candidate
Anti-infectives & inflammation
CLIENT
Phase 2
Phase 2b
One program
{
On hold: biological liability
Phase 1: 2009
Candidate selection: 2009
Lead declaration
Project starts: Q1
Hit structure: narrow activity spectrum
Racemic
Limited SAR
Undeveloped chemistry: unusual scaffold
No crystal structure
Q1: Validated
thigh model
Q3: Pre-candidate
#1 put on hold:
biological liability
Q1: ½ Kg
pre-candidate
synthesized
CASE STUDY
Anti-infective Program
= NAEJA
= CLIENT
Q1: Chemistry development, SAR, MIC panel
Q4: Racemic
lead #1 declared
Q1: Process development
Q3: Molecular modeling & SBDD
Q3: Crystal
structure
2007
Q1: Racemic
lead #2 declared
Q2: chiral HPLC
Candidate declaration
>98% purity
>98% eefffff
Q1: ADME
2008
2009
Hit Generation
and Validation
NAEJA
Hit to Lead
Lead
Optimization
Candidate
Successful Recent Programs
Phase 1b/2: Cardiovascular disease
Clinical trials: Pain management
Clinical trials: anti-bacterial
Clinical trials: anti-fungal
Alzheimer's program
Anti-viral program
Medicinal Chemistry Projects
Inflammation
Other
Papers 4
Patents 9
Papers 4
Patents 10
CNS
Antibacterial
Papers 42
Patents 19
Papers 3
CVD
Papers 5
Patents 1
Antifungal
Cancer
Papers 20
Patents 5
Antiviral
Papers 2
Patents 5
Papers 15
Patents 4
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.
Director
100% PhDs
Project
Coordinator
NAEJA FTE’s
Staffing
Chemistry: 71%
Biology: 7%
Analytical: 5%
Admin: 17%
PhDs & Postdocs by Training Location
100% PhDs
Scientist
90% PhDs
Canada
US
Europe
Asia
Japan
Locations of Ph.D.’s and Postdocs
Computational Chemistry Services
Hit Discovery:
ligand docking
Sybyl™, Glide/
pharmacophore generation
Schrödinger™
Lead Optimization:
Sybyl™, Glide/
ligand docking
QSAR
Schrödinger™
Physical Properties:
ACD™ software
pKa, log P, log D, & solubility
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)
Microbiology – in vitro studies
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
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
200 mice/40 rats - PK
Level II biohazard
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
Senior Director
Business & Development
Dr Chris Diaper
Associate
Business & Development
NAEJA Pharmaceutical Inc.
4290-91A Street, Edmonton, Alberta, Canada. T6E 5V2
Tel: (780) 462-4044; Fax: (780) 461-0196
E-mail: [email protected]
www.naeja.com