Recomendados
Mais conteúdo relacionado
Semelhante a NAEJA Presentation
Semelhante a NAEJA Presentation (20)
Último
Último (20)
NAEJA Presentation
- 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
- 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