International Research for Global Health NAEJA Pharmaceutical Inc. INTEGRATED MEDICINAL CHEMISTRY.
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Transcript of International Research for Global Health NAEJA Pharmaceutical Inc. INTEGRATED MEDICINAL CHEMISTRY.
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: [email protected]
www.naeja.com