A Canadian Success Story: Overcoming scientific and logistical problems in the

development of NeisVac-C

Dr. Harold J. JenningsNRC-IBS

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

Structures of The Capsular Polysaccharides of N. meningitidis

O ‖

6)-D-ManpNAc(1-O-P-O- 3 AcO

8)-D-NeupNAc(2

9)-D-NeupNAc(2 8 AcO

9)-D-NeupNAc(2

6)-D-Galp(14)-D-NeupNAc(2

6)-D-Glcp(14)-D-NeupNAc(2(contains OAc groups)

Group Structure

A

B

C

C(OAc-)

W-135

Y

N. meningitidis O-acetylated Group C polysaccharide

n

O

HO2C

HO

OHO

OH

HOAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO

HO

CO2H

OAc

HOAcHN

n

O

HO2C

HO

OAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO

HO

CO2H

OAc

HOAcHN

O

H

NaIO4

History of the Development of NRC Conjugate Vaccines

1990 NAVA Incorporated in Canada by merging BioChem/ NRC technology with AMVAX (U.S.). BioChem Pharma retained Canadian rights.

1992 NAVA/ NRC vs. American Cyanamid (Praxis). U.S. Courts of Appeal infringement of U.S. Patent 4,356,170.

N. meningitidis O-deacetylated Group C polysaccharide

n

O

HO2C

HO

OHO

OH

HOAcHN O

HO2C

HO

O

OH

HOAcHN O

HO2C

HO

O

OH

HOAcHN O

HO

HO

CO2H

OH

HOAcHN

O

HO2C

HO

O

O

AcHN O

HO2C

HO

O

HO

HOAcHN

O

H

H

m

NaIO4

N. meningitidis O-acetylated Group C polysaccharide

n

O

HO2C

HO

OHO

OH

HOAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO

HO

CO2H

OAc

HOAcHN

n

O

HO2C

HO

OAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO2C

HO

O

OAc

HOAcHN O

HO

HO

CO2H

OAc

HOAcHN

O

H

NaIO4

O

OHO

HO

P

O

O

O

OH

OH

OH

OH

n

H. influenzae type b polysaccharide

m

O

OHO

HO

P

O

O

O

OH

O

H

O

OHO

HO

P

O

O

O

OH

OH

OH

OHO

H

NaIO4

O

HO2C

HO

O

O

AcHN O

HO2C

HO

O

HO

HOAcHN

O

H

H

m

N. meningitidis O-deacetylated Group C polysaccharide

n

O

HO2C

HO

OHO

OH

HOAcHN O

HO2C

HO

O

OH

HOAcHN O

HO2C

HO

O

OH

HOAcHN O

HO

HO

CO2H

OH

HOAcHN

O

HO2C

HO

O

O

AcHN O

HO2C

HO

O

HO

HOAcHN

O

H

H

m

NaIO4

HPA (CDSC) E. Miller et al. 2003

Laboratory Confirmed Cases of Meningococcal Disease (by quarter) England & Wales.

History of the Development of NRC Conjugate Vaccines

2000 Baxter Int. acquired NAVA following marketing of Group C meningococcal vaccine.

2001 Shire acquired BioChem Pharma. Retained Canadian rights on NRC technologies.

2004 ID Biomedical acquired Shire’s vaccine business. Retained Canadian rights on NRC technologies

Prevalence of Group B Streptococcus disease isolates

Ia38.8%

Ib8.5%

II7.0%

III28.7%

V14.7%

VII0.8%NT

1.6%

→4)D-Glcp-(1→4)D-Galp-(1→ 3 ↑ 1

D-NeupNAc-(2→3)D-Galp-(1→4)D-GlcpNAc

→4)D-GlcpNAc-(1→3)D-Galp-(1→4)D-Glcp-(1→3)D-Glcp-(1→2)D-Galp-(1→ 6 3 ↑ ↑ 1 2

D-Galp D-NeupNAc

→4)D-Glcp-(1→6)D-GlcpNAc-(1→3)D-Galp-(1→ 4 ↑ 1

D-NeupNAc-(2→3)D-Galp

→4)D-Glcp-(1→4)D-Galp-(1→4)D-Glcp-(1→ 6 4 ↑ ↑ 1 1

D-NeupNAc-(2→3)D-Galp-(1→4)D-GlcpNAc D-Glcp

Structures of The Capsular Polysaccharides of Group B Streptococcus

Ia

Ib

III

II

V

→4)D-Glcp-(1→4)D-Galp-(1→ 3 ↑ 1

D-NeupNAc-(2→3)D-Galp-(1→3)D-GlcpNAc

Protection of infant mice by placentally transferredpolysaccharide (PS) specific antibody

Vaccine

Tetanus Toxoid (TT)

III PS

III PS and TT

III PS-TT Conjugate

Mothers Vaccinated

1

2

3

3

ProgenyChallenged

12

22

33

29

Survivors

0

0

0

27

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

“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

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

Royalty RevenuesRoyalties Received - by period (bar) and cumulative (line, x10)

$0.00

$500,000.00

$1,000,000.00

$1,500,000.00

$2,000,000.00

$2,500,000.00

$3,000,000.00

$3,500,000.00

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