Dr. Harold J. Jennings NRC-IBS

1. A Canadian Success Story: Overcoming scientific and logistical problems in the development of NeisVac-C Dr. Harold J. Jennings NRC-IBS

2. Age specific rates for meningococcal infection UK, Public Health Laboratory Services. Compiled by D. Jones

7. Structures of The Capsular Polysaccharides of N. meningitidis Group Structure O ‖ 6)-aD-ManpNAc(1-O-P-O- 3  AcO A 8)-aD-NeupNAc(2 B 9)-aD-NeupNAc(2 8  AcO C 9)-aD-NeupNAc(2 C(OAc-) 6)-aD-Galp(14)-aD-NeupNAc(2 W-135 6)-aD-Glcp(14)-aD-NeupNAc(2(contains OAc groups) Y

16. History of the Development of NRC Conjugate Vaccines • NAVA Incorporated in Canada by merging BioChem/ NRC technology with AMVAX (U.S.). BioChem Pharma retained Canadian rights. • NAVA/ NRC vs. American Cyanamid (Praxis). U.S. Courts of Appeal infringement of U.S. Patent 4,356,170.

22. Laboratory Confirmed Cases of Meningococcal Disease (by quarter) England & Wales. HPA (CDSC) E. Miller et al. 2003

23. History of the Development of NRC Conjugate Vaccines 2000 Baxter Int. acquired NAVA following marketing of Group C meningococcal vaccine. • Shire acquired BioChem Pharma. Retained Canadian rights on NRC technologies. • ID Biomedical acquired Shire’s vaccine business. Retained Canadian rights on NRC technologies

24. Prevalence of Group B Streptococcus disease isolates VII NT 0.8% V 1.6% 14.7% Ia 38.8% III 28.7% Ib II 8.5% 7.0%

25. Structures of The Capsular Polysaccharides of Group B Streptococcus →4)bD-Glcp-(1→4)bD-Galp-(1→ 3 ↑ 1 aD-NeupNAc-(2→3)bD-Galp-(1→4)bD-GlcpNAc Ia →4)bD-Glcp-(1→4)bD-Galp-(1→ 3 ↑ 1 aD-NeupNAc-(2→3)bD-Galp-(1→3)bD-GlcpNAc Ib →4)bD-GlcpNAc-(1→3)bD-Galp-(1→4)bD-Glcp-(1→3)bD-Glcp-(1→2)bD-Galp-(1→ 6 3 ↑ ↑ 1 2 bD-Galp aD-NeupNAc II →4)bD-Glcp-(1→6)bD-GlcpNAc-(1→3)bD-Galp-(1→ 4 ↑ 1 aD-NeupNAc-(2→3)bD-Galp III →4)aD-Glcp-(1→4)bD-Galp-(1→4)bD-Glcp-(1→ 6 4 ↑ ↑ 1 1 aD-NeupNAc-(2→3)bD-Galp-(1→4)bD-GlcpNAc bD-Glcp V

27. Protection of infant mice by placentally transferred polysaccharide (PS) specific antibody Vaccine Tetanus Toxoid (TT) III PS III PS and TT III PS-TT Conjugate Mothers Vaccinated 1 2 3 3 Progeny Challenged 12 22 33 29 Survivors 0 0 0 27

34. Recent history of the development of Group B meningococcal- conjugate vaccine 1999: Aventis Pasteur sub-licensed NRC technology for the development of a chemically modified group B meningococcal polysaccharide- conjugate vaccine 2002: Aventis Pasteur carried out a limited trial of the conjugate vaccine on a few male volunteers using alum as adjuvant (poor bactericidal activity) 2003: Aventis Pasteur dropped the above sub-license because of perceived safety concerns

35. “Further consideration by Aventis-Pasteur experts, in-house, led to the conclusion that there could be sustained difficulties for “proving” safety to licensing authorities and the general public. Moreover, because of the plausibility of the perceived risk, the vaccine could become the focus for anti-vaccine groups with a constant threat of litigation from those who “suspect” they may have been adversely affected.” 1 1: Decision by the Safety Consultation Committee- Aventis-Pasteur SA

36. Recent history of the development of Group B meningococcal- conjugate vaccine 2004: Baxter dropped the license to NRC technology on chemically modified group B meningococcal- conjugate vaccine 2004: BioVeris licensed NRC technology on chemically modified group B meningococcal- conjugate vaccine

39. Royalty Revenues