naeja presentation
TRANSCRIPT
Drug discovery Contract Research Organization (CRO)
Previously SynPhar (1987‐1999)
Privately owned
63,000 ft2 facility
Based in Edmonton, Canada
NAEJA Pharmaceutical Inc.North America, Europe, Japan, Asia
Europe
US
Japan
Large
PharmaBiotech
Longest collaboration
12 yearsLongest contract
4 years
NAEJA Pharmaceutical Inc.Client Base (2008‐2009)*
*(% revenue)
Design
Analysis Test
Synthesis
HIT CANDIDATE
NAEJA’s Role in Drug Discovery
–– InfrastructureInfrastructure– Expertise– Experience
Design
Analysis Test
Synthesis
Computational Computational ChemistryChemistry
Molecular modeling/QSARSurvey chemical space
Target libraries: defined physical properties
Infrastructure:
Computational Chemistry
• Hit Discovery:– ligand docking– pharmacophore generation
• Lead Optimization: – ligand docking– QSAR
• Physical Properties: – pKa, log P, log D, & solubility
Design
Analysis Test
Synthesis
Medicinal ChemistryMedicinal Chemistry
Review TPPReview SAR
Experience in design:ADME/DMPK/toxicity
Infrastructure:
Director100% PhDs
Project
Coordinator100% PhDs
Scientist90% PhDs
Staffing Chemistry: 71% Biology: 7%Analytical: 5% Admin: 17%
PhDs & Postdocs by Training Location
CanadaUSEuropeAsiaJapan
PhDs & Postdoc Training of NAEJA Scientists
Design
Analysis Test
Synthesis
Infrastructure:Synthetic ChemistrySynthetic Chemistry
Over 60 Ph.D. ChemistsReactions up to 22L scale
Access to SciFinder, ReaxysAccess to NMR, MS, LC‐MS, analytical and prep HPLC
Analytical & Purification Support
Purification
– Prep HPLC– Automated prep LC‐MS– Routine scale 100‐500 mg
– Semi‐prep NP/chiral– Routine scale 50‐100 mg
– Biotage– Routine NP/RP– Specialty columns also available
e.g. alumina, cyano, ion‐exchange
Analytical
– Chiral HPLC– CHIRALPAK™ AD, AD‐RH, OD, OD‐R,
OF, OB, OJ
– LC‐MS
– Elemental analysis, IR, & optical rotations
– 1H NMR– 2 × 400 MHz
Design
Analysis Test
Synthesis
Infrastructure:
Biological ServicesBiological Services
MicrobiologyDMPK
PharmacologyToxicity
Hit
Select Organism Microbiology– Time‐kill studies
– Post antibiotic effect (PAE) studies
– Frequency of resistance
Select Organism Microbiology– Time‐kill studies
– Post antibiotic effect (PAE) studies
– Frequency of resistanceRodent in vivo Efficacy– Superficial skin infection
– Pneumonia
– Septicemia
– Sepsis
– Thigh infection
Rodent in vivo Efficacy– Superficial skin infection
– Pneumonia
– Septicemia
– Sepsis
– Thigh infection
Candidate
Microbiology, DMPK& Toxicity
Primary MIC Panel– NCCL procedures
– Gram +ve and –ve
– Anaerobes
– Fungi
Primary MIC Panel– NCCL procedures
– Gram +ve and –ve
– Anaerobes
– Fungi Secondary Panel– MIC90’s
– > 4000 clinical isolates
– Includes 2009 strains
Secondary Panel– MIC90’s
– > 4000 clinical isolates
– Includes 2009 strains
In vitro PK– Physicochemical
properties
– Chemical & metabolic Stability
In vitro PK– Physicochemical
properties
– Chemical & metabolic Stability
In vitro Toxicity– hERG
– CYP 450 panel
In vivo Safety and PK– Acute/sub acute dosing
– Cmax, Tmax, Vd, t½, AUC, %F
In vitro Toxicity– hERG
– CYP 450 panel
In vivo Safety and PK– Acute/sub acute dosing
– Cmax, Tmax, Vd, t½, AUC, %F
In vivo Pharmacology ModelsSepticemia
– Staphylococcus aureus MRSA– Staphylococcus Aureus MSSA– Candida albicans– Aspergillus fumigatus
Thigh infections
– Staphylococcus aureus MRSA– Staphylococcus aureus MSSA– Streptococcus pneumoniae– Escherichia coli
Pneumonia
– Streptococcus pneumoniae
– Aspergillus fumigatus
Sepsis
– Staphylococcus aureus MRSA
– Staphylococcus aureus MSSA
– Escherichia coli
Superficial skin infection
– Staphylococcus aureus MSSAAnimal Facilities (CCAC): Level II biohazard
Pharmacokinetics
in vitro
– Aqueous solubility– Partition coefficients– Plasma protein binding– A‐B permeability (MDCK)– Metabolic stability (microsomes,
hepatocytes)– UPLC‐MS‐MS screening
in vivo
– Bioavailability studies– Blood/plasma concentrations– Tissue concentration/distribution– Metabolite profiling
Animal facilities adhere to CCAC
Design
Analysis Test
Synthesis
Infrastructure:
Scientific SupportScientific Support
Internal: DirectorsMinimum industrial experience – 15 years
External: Consultants Specific TAs/disciplines
Design
Analysis Test
Synthesis
HIT CANDIDATE
NAEJA’s Role in Drug Discovery
– Infrastructure–– ExpertiseExpertise– Experience
Design
Analysis Test
Synthesis
AntiAnti‐‐infectivesinfectives::TazobactamTazobactam
β‐Lactamase InhibitorCollaboration with TaihoMarketed by Wyeth/Pfizer
Track Record:
Design
Analysis Test
Synthesis
Track Record:AntiAnti‐‐infectivesinfectives::SYNSYN‐‐21902190
Licensed: Anti‐infective Diagnostics
WO 2009/051838
Design
Analysis Test
Synthesis
Track Record:Mofezolac Mofezolac (Disopain(Disopain™™))
Commercial NSAIDCollaboration with TaihoMarketed by Mitsubishi
Design
Analysis Test
Synthesis
Track Record:Published TAs:
Anti‐Infectives:TopoisomerasesDNA gyraseβ‐LactamasesHistidine kinasePPB3, PDK, LeuRS
Efflux pump inhibitors
Design
Analysis Test
Synthesis
Track Record:Cardiovascular Targets:Antihypertensives ‐ ReninAnticoagulants ‐ Factor Xa
Cancer:Cyclin‐dependant kinase Cdk4
Dermatology:Androgen receptors
CNS:NRI’s and 5‐HT1A
Inflammation:TNF‐α, IL‐23, & PDE4
Design
Analysis Test
Synthesis
Track Record:
Recent Publications:
MIC screeningBioorg. Med. Chem. Lett.
2009, 19, 1292, 3374, & 4626
ICAAC 2009 Poster:
Efficacy study: MRSA mouse skin infection model
Design
Analysis Test
Synthesis
Track Record:
Scientific Support
Internal: Sr. DirectorsMedicinal Chemistry
Dr Rajeshwar Singh52 papers; 46 patents
Dr S. N. Maiti58 papers, 15 patents
Design
Analysis Test
Synthesis
Track Record:
AntiinfectivesAntifungalsCVCancerInflammationMental HealthCOPDAuto ImmuneSynthesisAnalytical
Papers and Patents238 in total
Design
Analysis Test
Synthesis
Track Record:
External Consultants
Dr John DomagalaSenior Consultant with IDSC
Previous position:Executive Director at Pfizer
Prof. Mike James FRSUniversity of Alberta
Crystallography & Modeling
Design
Analysis Test
Synthesis
HIT CANDIDATE
NAEJA’s Role in Drug Discovery
– Infrastructure– Expertise–– ExperienceExperience
Single Client – Concurrent Anti‐infectives& Inflammation Programs
NAEJA
Hit Generation
and ValidationHit to Lead Lead
Optimization
Cand
idate
CLIENT Phase 2
Phase 3
Phase 1: 2009
On hold: biological liability
Candidate selection: 2009
Lead declaration: 2009
{One program
Other Successful Recent Programs
NAEJA
Hit Generation
and ValidationHit to Lead Lead
Optimization
Cand
idate
Phase 1b/2: Cardiovascular disease
Clinical trials: anti‐fungal
Alzheimer's program
Anti‐viral program
Clinical trials: Pain management
Clinical trials: anti‐bacterial
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
Q1: Racemic lead #2 declared
Q1: Racemic lead #2 declared
Q3: Molecular modeling & SBDDQ3: Molecular modeling & SBDD
CASE STUDYAnti‐infective Program
= NAEJA
= CLIENT
Q1: ADMEQ1: ADME
Q2: chiral HPLCQ2: chiral HPLC
Q1 to Q4 2009
Biochemistry
Q1 to Q4 2009
Biochemistry
NAEJA Business Models
Compound based fee‐for‐service
Custom SynthesisDiscovery Biology
Program based Drug discovery
FTE R&D Service
Design
Analysis Test
Synthesis
NAEJA Packages:Compound based fee‐for‐service
– Short term– Fixed deliverables– All materials & labor included– Literature searches included– Client owns 100% of the IP
Design
Analysis Test
Synthesis
Program Research:FTE based R&D Service– Staffing
– 1 computational chemist– 5 synthetic/medicinal chemists– 1‐2 biologists
– Time frame– 6‐12 months lead generation– 1‐2 years lead optimization
– Client owns 100% of the IP
– Included in FTE price– Consumables– Literature/patent searching–Waste disposal
Contact Information
Dr. Sameeh SalamaSenior Director, Business Development
Dr. Chris Diaper Business Development Associate
NAEJA Pharmaceutical Inc.4290‐91A Street, EdmontonAlberta, Canada. T6E 5V2Tel: (780) 462‐4044Fax: (780) 461‐0196E‐mail: [email protected]