VaxInnate's Seasonal Flu Vaccine Candidate Shown Safe and Immunogenic in Phase I Study

Novel Technology Could Transform Flu Vaccine Production

BALTIMORE--(BUSINESS WIRE)--Apr 27, 2009 - An investigational flu vaccine based on a novel technology that could dramatically improve the potency, manufacturing capacity and cost effectiveness of flu vaccines, was safe and immunogenic in a Phase I trial presented at the National Foundation for Infectious Diseases' (NFID) Twelfth Annual Conference on Vaccine Research here today.

The new data support the potential of VAX125, VaxInnate's investigational hemagglutinin (HA)-flagellin flu vaccine, to rapidly meet global vaccination needs, something not possible today using conventional egg- or cell-based vaccines that require months to produce. VAX125 is the H1 component of what would ultimately be a trivalent seasonal flu vaccine.

“VaxInnate's HA vaccine candidate for seasonal flu has passed a critical initial test,” said David Taylor, MD, Chief Medical Officer. “We're encouraged by these data, which show that VAX125 is safe and elicits a potent immune response at sub-microgram doses. That's particularly impressive when you consider that the dose of conventional flu vaccines in use today is 15 micrograms for each component.”

The investigational HA–flagellin flu vaccine is the product of VaxInnate's proprietary combination of toll-like receptor (TLR)-mediated immune enhancement and recombinant bacterial production of vaccine antigen.

VAX125 Safety & Immunogenicity Data

Conducted in two parts, the Phase I study was designed both to assess the safety and immunogenicity – a patient's ability to make an immune response – of different doses of VAX 125 and to select the optimal dose for use in a trivalent vaccine.

VAX125 links the H1 Solomon Island hemagglutinin (HA) antigen, the key protective component used in flu vaccines for many years, to flagellin. Flagellin is a bacterial protein that interacts with the immune system's toll-like receptors (TLRs) to enhance VAX125's immunological potency.

Part 1 was an open-label, escalating, dose-ranging Phase I study that assessed the safety and immunogenicity of seven doses (0.1, 0.3, 1, 2, 3, 5 and 8ug) of VAX125 in 56 healthy adults aged 18-49.

Each of the seven VAX125 dosage levels was given as a single intramuscular dose to eight subjects. Clinical and laboratory safety assessments took place one and seven days after immunization; immune response to VAX125 was assessed 0, 7, 14 and 28 days after immunization. Seroresponse was defined as a serum anti-HA antibody titer of ‰¥ 1:40 and a four-fold rise in titer. Seroprotection was defined as an achievement post- vaccination of an anti-HA titer of ‰¥ 1:40 in those subjects who presented with a pre-vaccination titer of < 1:40.

All seven doses were safe and well tolerated, with one subject in the 3 µg dose group experiencing flu-like symptoms. VAX125 exhibited a seroresponse in 5 (31%) of the 16 vaccinees in the low-dose group (0.1 or 0.3 µg doses), 12 (50%) of the 24 vaccinees in the mid- dose group (1, 2 or 3 µg doses), and 12 (75%) out of 16 vaccinees in the high-dose group (5 µg or 8 µg doses). Seroprotection was seen in 13 of 14 (93%) subjects with pre-vaccination titers <1:40.

Selection of Optimal Dose for Trivalent Vaccine

Part 2 was a randomized, placebo-controlled, blinded study designed to assess the safety and immunogenicity of the 1 µg and 2 µg doses and to select the optimal dose for a trivalent vaccine.

Forty-eight healthy adults aged 18-49 were randomized into three groups to receive a single intramuscular dose of 1 µg (16 subjects) and 2 µg (16 subjects) compared to placebo (16 subjects). Clinical and laboratory safety assessments took place 0, 14 and 28 days post-immunization. Both doses were safe and well tolerated. Seroresponse was seen in 8 (50%) of the 16 subjects at the 1.0 µg dose, and in 13 (81%) of the 16 subjects at the 2.0 µg dose. Seroprotection was noted in 3 of 4 (75%) subjects, and in 5 of 5 (100%) subjects at the 1.0 µg and 2.0 µg doses, respectively.

Given the antibody responses and the absence of significant adverse reactions, VaxInnate intends to continue development and clinical evaluation of the vaccine candidate for use in a trivalent vaccine formulation.

“In this study, VAX125 was well tolerated and highly immunogenic at doses as high as 8 µg,” said primary investigator John Treanor, MD. “A trivalent formulation of 0.5 to 1 µg per component for a total dose of 1.5 to 3 µg falls well within the range that was shown to be well tolerated in healthy subjects. Based on these results, VAX125 could represent a new option for preventing or attenuating seasonal influenza.”

Dr. Treanor, who has a long standing interest in influenza pathogenesis and vaccine development, also serves as Professor of Medicine and Professor of Microbiology and Immunology at the University of Rochester School of Medicine and Dentistry.

VaxInnate's Approach and VAX125

Epidemiologists developing traditional flu vaccines must predict months in advance which flu strains will be circulating during the next fall/winter season to formulate a vaccine that targets the likeliest candidates. That's because hemagglutinin (HA), a vaccine antigen that has been used in flu vaccines for many years, changes over time, in turn forcing manufacturers to change the strains of HA included seasonal flu vaccines.

The selected flu strains are manufactured in live, fertilized chicken eggs using a laborious process that takes six to nine months. Federally-funded alternative approaches in development, such as cell-based production, take nearly as long and require large, committed manufacturing facilities for vaccine production.

The time necessary to manufacture flu vaccine using eggs or cells makes it virtually impossible to reformulate vaccine should circulating strains not match those in the seasonal vaccine, as was the case most during the 2007-2008 flu season. Problems in growing virus strains have also resulted in vaccine shortages early in flu season, when most vaccination takes place.

Unlike egg- or cell-based vaccine production, VaxInnate's technology is based upon the expression in recombinant bacteria of relevant influenza virus protein antigens – in this case, HA -- fused to the bacterial protein flagellin. Flagellin interacts with the immune system's toll-like receptors (TLRs), which function in human immune cells like sentries to detect pathogens and trigger a general immune defense. This initial defense releases cytokines and other signals that in turn stimulate a second, stronger adaptive immune response, including production of pathogen-specific antibodies.

This new technology could produce potent flu vaccine that can be produced rapidly and cheaply in volumes sufficient to meet national and global needs, and be suitable for stockpiling.

About VaxInnate

VaxInnate is a privately-held biotechnology company in Cranbury, NJ that is pioneering breakthrough technology for use in developing novel and proprietary vaccines. VaxInnate's technology has the potential to dramatically improve the potency, manufacturing capacity and cost-effectiveness of vaccines.

VaxInnate's first vaccines focus on infectious diseases, including seasonal and pandemic flu, malaria, dengue and respiratory syncytial virus. In 2008 and 2009, VaxInnate generated positive Phase I clinical data for its first two vaccines, a universal flu vaccine and a seasonal flu vaccine.

VaxInnate's technology platform is also being investigated for development of vaccines for other diseases. For more information about VaxInnate, please visit http://www.vaxinnate.com.

 

Contact: VaxInnate Janet Skidmore, 215-658-4915 Mobile: 215-429-2917 skidmorecomm@earthlink.net

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Posted: April 2009

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