Presentation Transcript

1. NAEJA Pharmaceutical Inc. INTEGRATED MEDICINAL CHEMISTRY International Research for Global Health

2. Drug discovery Contract Research Organization (CRO) • Previously SynPhar • Privately owned • 63,000 ft2 facility • Based in Edmonton, Canada

4. Core ExpertisePre-Clinical Development IND & Clinical Trials Lead Optimization Target Validation HIT Validation Lead Identification

5. Track Record

6. Success Stories: Anti-infectives SYNPHAR TAIHO IND & Clinical Trials Lead Optimization HIT Validation Lead Identification Tazobactam Design, Synthesis, & Screening of -Lactamase Inhibitor 4 Year Program Collaboration with Taiho Pharmaceuticals Marketed by Wyeth

7. Success Stories: Inflammation SYNPHAR TAIHO IND & Clinical Trials Lead Optimization HIT Validation Lead Identification Mofezolac (DisopainTM) Design & Synthesis of NSAID 4 Year Program Collaboration with Taiho Pharmaceuticals Marketed by Mitsubishi Pharmaceuticals

8. NAEJA Track Record Past 5 Years* Large Pharma Biotech New market 2008 Longest collaboration 12 years Longest contract 4 years Multiple projects & clients Proven IP security *(% revenue)

9. Single Client – Multiple ProgramsAnti-infectives & inflammation Lead Optimization Hit Generation and Validation Hit to Lead Candidate CLIENT NAEJA Phase 2 Phase 2b { On hold: biological liability One program Phase 1: 2009 Candidate selection: 2009 Lead declaration

10. CASE STUDY Anti-infective Program = NAEJA = CLIENT 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 Q1: Chemistry development, SAR, MIC panel Q1: Process development Q4: Racemic lead #1 declared Candidate declaration >98% purity >98% eefffff Q3: Molecular modeling & SBDD Q2: chiral HPLC Q1: ADME Q3: Crystal structure Q1: Racemic lead #2 declared 2007 2008 2009

11. Successful Recent Programs Lead Optimization Hit Generation and Validation Hit to Lead Candidate NAEJA Phase 1b/2: Cardiovascular disease Clinical trials: Pain management Clinical trials: anti-bacterial Clinical trials: anti-fungal Alzheimer's program Anti-viral program

12. Medicinal Chemistry Projects Papers 4 Patents 9 Papers 4 Patents 10 Papers 42 Patents 19 Papers 3 Papers 5 Patents 1 Papers 15 Patents 4 Papers 2 Patents 5 Papers 20 Patents 5

13. Services

14. 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.

15. NAEJA FTE’s Director 100% PhDs StaffingChemistry: 71% Biology: 7% Analytical: 5% Admin: 17% PhDs & Postdocs by Training Location Project Coordinator 100% PhDs Scientist 90% PhDs

16. Locations of Ph.D.’s and Postdocs

17. Computational Chemistry Services Hit Discovery: ligand docking Sybyl™, Glide/ pharmacophore generation Schrödinger™ Lead Optimization: ligand docking Sybyl™, Glide/ QSAR Schrödinger™ Physical Properties: pKa, log P, log D, & solubility ACD™ software

18. 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)

19. 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

20. 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

21. 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

22. Animal Facilities (CCAC)* Capacity: Conventional housingLevel II biohazard200 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

23. 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)

24. 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.

25. Contact Information Dr Sameeh Salama Dr Chris Diaper Senior Director Associate Business & 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