rPA anthrax vaccine and its Valortim anthrax anti-toxin program data presented

Sep 4 2009

PharmAthene, Inc. (NYSE Amex: PIP), a biodefense company developing medical countermeasures against biological and chemical threats, announced today that data from the Company's third generation recombinant protective antigen (rPA) anthrax vaccine program and its Valortim((R)) anthrax anti-toxin program were presented at the Bacillus - ACT 2009 meeting, August 30 - September 3, 2009, organized by the American Society for Microbiology.

David P. Wright, President and Chief Executive Officer of PharmAthene commented, "Preliminary data from our third generation (3G) rPA anthrax vaccine program suggest that a 3G product prototype may be able to provide a more rapid onset of immunity and enhanced immunogenicity than the currently available anthrax vaccine, suggesting the potential for a vaccine that can be given in fewer doses than is required today."

"Additionally, new data from our Valortim((R)) program were presented highlighting the potential for Valortim((R)) as a promising new therapeutic for anthrax. In the African Green Monkey (AGM) model, up to 70% of Valortim((R))-treated animals survived inhalational challenge with anthrax spores. A second poster, presented additional studies in immunodeficient mouse models, and demonstrated the unique activity of Valortim((R)) in protecting these mice from being killed by B. anthracis. These data suggest a potential unique mechanism of action for Valortim(TM) that will need to be substantiated in additional studies," continued Mr. Wright.

Valortim((R)), which is being co-developed by PharmAthene and Medarex, Inc., is a fully human monoclonal antibody designed to protect against and treat inhalational anthrax, the most lethal form of illness in humans caused by anthrax.

Valortim((R)) Findings Presented

Dr. Alan Cross, Professor of Medicine and Dr. Subhendu Basu, Assistant Professor of Medicine, University of Maryland School of Medicine, presented data in a poster entitled, "Mechanisms of an anti-PA Antibody (Valortim((R))) that Mediate Protection Against B. Anthracis Infection." The aim of the studies was to determine if the protection against anthrax infection provided by Valortim((R)) was mediated by the immune system.

Study investigators challenged mice with an impaired innate immune system with B.anthracis, with and without Valortim((R)). Their results demonstrated that Valortim((R)) conferred protection to the mice.

In a separate study, mice that lacked an adaptive immune system (devoid of T and B cells) were challenged to establish the role of the cellular immune response in Valortim((R))-mediated protection. Results showed that Valortim((R)) protected these mice at an early time point, post lethal B. anthracis challenge. Study results therefore showed that mice with both impaired adaptive or innate immune responses were protected by Valortim((R)) from a B. anthracis challenge.

Dr. Cross' team concluded that Valortim((R)) supports the ability of innate and adaptive immune responses to control B. anthracis infection. Previous studies have also suggested that Valortim((R)) may play a direct role in killing B. anthracis.

Dr. Cross remarked, "These new data, which augment results from our earlier studies, further highlight the potentially unique activity of Valortim((R)), given its ability to apparently kill B. anthracis, as well as support the immune system's response to anthrax infection."

The work reported by Dr. Cross is supported by the Maryland Industrial Partnerships Program (MIPS). The MIPS program was developed to accelerate the commercialization of technology in Maryland by jointly funding collaborative R&D projects between companies and University System of Maryland faculty.

Separately, Dr. Louise Pitt, Director, Center for Aerobiological Sciences, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), presented data in a poster entitled, "Therapeutic Efficacy of Valortim((R)) an Anti-toxin Monoclonal Antibody, in the African Green Monkey Model of Inhalational Anthrax." Inhalational anthrax in certain primates such as African Green Monkeys (AGMs) is believed to follow a similar disease course as in humans.

In this randomized, blinded study, 48 AGMs were exposed by aerosol to Ames anthrax spores and blood samples were collected every 8 hours, beginning 24 hours post-exposure, to assess antigenemia (protective antigen 'PA' in circulation) and bacteremia. Samples were assayed for PA by a rapid electrochemiluminescence immunoassay (ECL), and bacteremia was confirmed by culture. The presence of PA in the blood of infected animals was the trigger for initiation of treatment with normal saline control, or Valortim((R)) at doses of 5, 10, 20 or 40 mg/kg.

In the study, AGMs were exposed by aerosol to Ames spores (approximately 200 LD(50)). Up to seventy percent (70%) of the Valortim((R))-treated animals survived. All AGMs were bacteremic at the time of treatment. These data suggest that Valortim((R) )may be a promising therapy for inhalational anthrax in symptomatic individuals and may have utility for use as rescue therapy.

The therapeutic efficacy study of Valortim((R)), given as a monotherapy in the AGM model, is being conducted by PharmAthene and its collaborators at USAMRIID, and has been funded in whole or in part with Federal funds from the Department of Defense through the United States Army Medical Research Institute of Infectious Diseases.

Third Generation (3G) rPA Anthrax Vaccine Findings Reported

Various government agencies, including the Institute of Medicine, have acknowledged the urgent need to stockpile next-generation anthrax vaccines employing modern vaccine technology, which offer the potential for improved safety and convenience, as well as enhanced characterization and lot-to-lot consistency. PharmAthene's portfolio includes both second and third generation rPA anthrax vaccine candidates, which incorporate significant product development and technological advancements and are designed to meet these requirements. The Company's second generation rPA anthrax vaccine, SparVax(TM), is currently under consideration for a major advanced development and procurement contract through the Biomedical Advanced Research and Development Agency.

The goal of PharmAthene's third generation (3G) rPA vaccine program is to develop a vaccine formulation which can induce a more rapid onset of protective immunity in fewer doses, and can be stored, transported and used without the need for a conventional cold chain - an important advantage for civilian biodefense deployment within the Strategic National Stockpile.

In a poster entitled, "Faster Time to Immunity and Enhanced Immune Response to Optimized rPA Vaccine," Allan Watkinson, R&D Director & Principal Investigator, PharmAthene UK, presented results from a mouse model in which PharmAthene and its collaborators investigated incorporating an additional immunostimulant adjuvant into a prototype 3G product formulation.

In the study, female mice were immunized in four treatment groups of 30 and blood samples were taken on days 14, 21 and 28. When immunization of mice with the lyophilized formulation of rPA was supplemented with the immunostimulant adjuvant, a significantly enhanced (p<0.005) anti-PA titre was induced, compared with the equivalent formulation lacking this adjuvant. Results showed that animals immunized with these formulations, whether supplemented with the adjuvant or not, were fully protected against challenge with 10(3 )median lethal doses of B. anthracis at day 21.

These preliminary data suggest that PharmAthene's 3G product prototype may be able to provide both faster time to immunity and significantly enhanced immunogenicity, indicating that the optimized formulation may be able to reduce the requirement for multiple vaccine doses, and simplify the immunization regimen for anthrax vaccines in the future.

Funding for this study was provided under a Challenge grant from the National Institutes of Health. The data from this study are intended to inform ongoing efforts in PharmAthene's 3G rPA program. In September 2008, PharmAthene was awarded a development contract from the National Institute of Allergy and Infectious Diseases (NIAID) of up to $83.9 million for the 3G rPA vaccine program, provided the government exercises all contract options at its sole discretion.