Vaccine AV0328

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.

Read more on the impact of current pneumococcal vaccines on S. pneumoniae Infections in the US - https://academic.oup.com/jid/article/226/2/342/6575225

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.

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.