Vaccine AV0328

A Targeted Vaccine

AV0328 is a synthetic PNAG. A phase 1, first-in-man trial has been completed and the vaccine was found to be well tolerated, and no serious adverse events were observed. It induced antibodies that were capable of killing a wide range of PNAG-expressing pathogens. In vitro efficacy in killing (by utilization of a validated surrogate assay-opsonic killing mediated by antibodies induced by AV0328) was noted against every pathogen tested which included over 10 microbial species. These included several Streptococcus pneumoniae serotypes including ones not covered by current vaccines. This has permitted us to pursue a unique approach.

Microbe Strain Outcome
N. gonorrhoeae UNC25
A442089
15253
H041
CTR-SPAIN
POS
POS
POS
POS
POS
N. meningitidis Serogroup A Z2087 POS
N. meningitidis Serogroup B B16B6
M2996
NMB
H44/76
M981
M992
POS
POS
POS
POS
POS
POS
N. meningitidis Serogroup C 89-1 POS
N. meningitidis Serogroup W W171 POS
N. meningitidis Serogroup X BF POS
N. meningitidis Serogroup Y Y2220 POS
A. baumannii S1 POS
C. albicans SC5314 POS
S. pneumoniae TIGR 4 (4)
Spn 6B (6B)
246 (14)
EF3030 (19F)
11865 (9V)
Spn 212 (22F)
Spn 255 (31B)
Spn 080 (8)
POS
POS
POS
POS
POS
POS
POS
POS
S. aureus MN8 (CP8) POS
MRSA USA300 (No CP)
USA100 (CP5)
Sanger 256 (CP8)
POS
POS
POS
E. coli NDM1
MCR1
POS
POS
K. pneumoniae Z2087 POS
S. typhi TY2 POS

AV0328 Pipeline

Compound Indication Discovery Pre-Clinical Phase 1 Phase 2 Phase 3

AV0328

S. pneumoniae infections

Discovery Phase complete
Pre-Clinical Phase complete
Phase 1 Phase in progress
Phase 2 Phase not started
Phase 3 Phase not started

AV0328

Meningococcal infections

Discovery Phase complete
Pre-Clinical Phase complete
Phase 1 Phase in progress
Phase 2 Phase not started
Phase 3 Phase not started

Prevention of Infections Caused by Streptococcus pneumoniae: Current Status

Conventional vaccines while effective are highly specific. This is the case with pneumococcal vaccines such as Prevnar which while effective cover only a fraction of the 100 or more subtypes or serotypes of Streptococcus pneumoniae. Prevnar 13 is called Prevnar 13 because it covers 13 serotypes. Following the introduction of Prevnar there was a rise in infections by the uncovered serotypes - a phenomenon known as serotype replacement. That has dictated the need to create newer vaccines that cover progressively more serotypes. Prevnar 7 was replaced by Prevnar 13 and now Prevnar 20 Other competitors are trying to develop vaccines that cover 24 or 30 serotypes.

These newer vaccines will continue to create the same problem – the rise in infections caused by the remaining 70-80 serotypes. This approach cannot continue. There is a limit to the number of individual components that can be packed into single serotype specific vaccine and the cost would be prohibitive.

Alopexx’s vaccine is a single antigenic component that can expand coverage well beyond the specific serotypes that existing pneumococcal vaccines target.

Serotypes Causing Majority of S. pneumoniae Infections in Adults Before and After Prevnar7 and Prevnar13 Introduction

A Unique Approach

Vaccine AV0328 to COMPLEMENT the coverage provided by current and future serotype-specific vaccines

PNAG has been noted to be expressed by 100% of the 36 pneumococcal strains tested to date. These include all serotypes contained in Pneumovax and the recently approved Prevnar 20 vaccine. Of the close to 250 distinct microbial strains that have been analyzed for PNAG expression >90% were positive. Consistent with our results with other pathogens, we expect that the majority of remaining pneumococcal serotypes will be positive for PNAG as well.

AV0328 has the potential to be a single, non-serotype specific, polysaccharide vaccine capable of covering most, if not all, pneumococcal serotypes. NO other currently available serotype-specific pneumococcal vaccine or any others in development are capable of offering this degree of coverage. This broad-spectrum potential has led us to follow a unique regulatory approval approach. As an initial indication, we plan to have AV0328 serve as a complementary vaccine that can expand coverage to many of the remaining 80+ S. pneumoniae serotypes not covered by current vaccines.

Most critically, we have been in contact with the FDA where we proposed this complementary approach. Feedback from the FDA has been supportive of the utilization of AV0328 as a complementary vaccine. In addition, the FDA supported pursuing accelerated approval of AV0328 based on safety and utilization of a validated surrogate assay – opsonic killing mediated by antibodies induced by AV0328.

This points to a development path comparable to those that have led to FDA approval of other vaccines for Streptococcus pneumoniae infections.

Expression of PNAG by S. pneumoniae in infected human lung

Based on feedback from the FDA and an Expert Panel there is a now a developmental road map for use of AV0328 in the prevention of S. pneumoniae infections

Proposed Indication

“AV0328 is indicated for adults 18 years of age and older for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes not covered by serotype-specific vaccines”


Red = antibody to S. pneumoniae cells;
Green = MAb to PNAG

Comparative Immunogenicity

Immunization with AV0328 Provides Comparable Levels of Opsonic Killing

AV0328 Prevnar-13 SP007 - Pooled Reference Sera

A

B

C

Dotted line represents Opsonic Killing Titer


Comparison of immune response induced to AV0328 with those elicited by immunization with Prevnar 13 against Prevnar and non-Prevnar S. pneumoniae serotypes.

Opsonic Killing (OPK) activity was measured before and after AV0328 immunization (Fig A) and Prevnar-13 immunization (Fig B). Results with a pooled reference sera SP007 are shown in Figure C.

Based on the accepted titer threshold (see dotted line) of 1:8 killing ≥ 50% of the bacterial cells being indicative of protection, AV0328 was able to induce protective levels of antibody as reflected in the opsonic killing titers against all tested S. pneumoniae serotypes.

By that definition, AV0328 demonstrated consistent killing against all S. pneumoniae serotypes tested. As PNAG is likely expressed on the vast majority S. pneumoniae serotypes we anticipate we will be able to achieve broad spectrum protective immunity.

Prevention of Meningococcal Infections

Meningococcal disease is caused by the bacterium Neisseria meningitidis. According to the Centers for Disease Control and Prevention (CDC), 1,000 to 2,600 people contract meningococcal disease each year in the United States. One in 10 of these cases results in death and serious health problems occur in 11 to 19 percent of survivors such as loss of limbs, deafness, nervous system problems, cognitive deficiencies, seizures and strokes. While rare it is highly contagious. The majority of U.S. states have mandated immunization for populations at risk - infants, people with certain medical conditions, college freshmen living in dorms, and teenagers, according to the NCSL. Because of the rarity and severity of the disease approval of meningococcal vaccines is based on serologic assays – the serum bactericidal assay (SBA). Six serogroups account for most disease cases worldwide. While there are several vaccines approved in the United States, none covers all six serogroups. Vaccination with AV0328 is able to induce bactericidal killing, as measured by SBA, of all six serogroups and could either complement or replace current vaccines.

Vaccine Company Serogroup
A B C W135 X Y
Menactra Sanofi X X X X
Menomune Sanofi X X X X
Menveo GSK X X X X
Bexsero GSK X
Trumenba Pfizer X
AV0328 Alopexx X X X X X X

Posters & Publications

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