September 24, 2008
PharmAthene Presents Data for Protexia(R) and Valortim(R) at 2008 BARDA Industry Conference / PHEMCE Stakeholders Workshop
ANNAPOLIS, Md., Sept. 24 /PRNewswire-FirstCall/ -- PharmAthene, Inc. , a biodefense company developing medical countermeasures against biological and chemical threats, announced today that the Company is presenting two posters and an oral presentation on its medical countermeasures programs, Protexia(R) (rBChE) and Valortim(R) at the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) Stakeholders Workshop 2008 / BARDA Industry Day being held in Alexandria, VA, September 24 - 26, 2008.
David P. Wright, President and Chief Executive Officer of PharmAthene commented, "We want to commend BARDA's new leadership for moving forward aggressively to engage with industry as a partner, and for their commitment to providing greater transparency and a long-term strategy for biodefense medical countermeasures research, development and procurement."
"We are delighted to have the opportunity to present these data at the PHEMCE conference, which is an important industry meeting for companies in the biodefense sector. As the data illustrate, PharmAthene continues to advance its pipeline and further its leadership position in biodefense by working collaboratively with the U.S. government to develop unique animal models that can potentially accelerate product commercialization," Mr. Wright continued.
Protexia(R), a recombinant version of human butyrylcholinesterase (BChE), is being developed as a pre- and post-exposure therapy for casualties on the battlefield or civilian victims of nerve agent attacks. Valortim(R), in co-development with Medarex, Inc., is a fully human monoclonal antibody designed to treat and protect against inhalational anthrax. Highlights of the poster presentations include:
-- A study of non-pegylated recombinant BChE in a guinea pig model provides new data that suggests that the pegylated rBChE (Protexia(R)) may have efficacy as a therapeutic against nerve agent exposure.
-- A study of Valortim(R) in a primate animal model utilizing the African green monkey (AGM) shows promise as a potential therapeutic for the treatment of inhalational anthrax.
-- A summary of the Valortim(R) development program, including previously reported Phase I data demonstrating that Valortim(R) is safe and well-tolerated, with no drug-related Grade 2-4 or serious adverse events supporting the potential of Valortim(R) as a promising therapy for treatment and post-exposure prophylaxis for inhalational anthrax.
Summary of Data Presented: Non-pegylated rBChE Findings Reported
In a poster entitled, "Recombinant Butyrylcholinesterase (rBChE) Therapy Following VX Poisoning by the Percutaneous Route: Preliminary Results from Guinea Pig Studies," investigators studied the effects of non-pegylated rBChE administered following poisoning by VX in an animal model which mimics percutaneous exposure. In this model, free agent was measured in both the dermis and blood enabling investigation of their temporal relationships. Non-pegylated rBChE significantly reduced the concentration of free VX in the blood. At 7.5 hours the cholinesterase activity of the plasma was approximately 27 fold greater than control. Additionally, brain cholinesterase levels were similar to previously published data from untreated controls suggesting that non-pegylated rBChE prevented the inhibition of these tissues by VX. The reduced concentration of circulating free VX following poisoning by the percutaneous route in animals treated with non-pegylated rBChE supports the conclusions of an earlier study (Mikler et al, 2007) that rBChE has potential utility as a post poisoning therapy. The investigators suggest that the data provide the first tangible evidence of the predicted mechanisms of post poisoning intervention with rBChE.
"The majority of our research to date for Protexia(R) has focused on studying its efficacy as a pre-exposure prophylactic. The promising preliminary data are particularly encouraging as they demonstrate that the non-pegylated rBChE may also be efficacious as a therapeutic for nerve agents. We plan to undertake further confirmatory work with Protexia(R) to build upon these exciting preliminary observations," said Mr. Wright.
Valortim(R) Findings Reported
In a poster entitled, "Efficacy of Intravenous Valortim(R), an Anti-toxin Monoclonal Antibody, in the Treatment of Inhalation Anthrax in the African Green Monkey Model," investigators at USAMRIID sought to refine the AGM as a therapeutic model by assessing the efficacy of an anti-toxin monoclonal antibody. In the study, 21 adult AGMs were exposed by aerosol to Ames anthrax spores and blood samples were collected every 4-8 hours beginning 24-hours post exposure to assess anthrax bacteremia and protective antigen in blood. Samples were analyzed for protective antigen via a rapid electrochemiluminescent immunoassay (ECL) and bacteremia was evaluated by 24-hour culture. In the study, 6 AGMs were treated with one intravenous dose of 10 mg/kg Valortim(R) when positive by ECL; a second cohort of 6 AGMs was treated with 2 intravenous doses of 10 mg/kg Valortim(R) (the first given when positive by ECL and the second dose administered 24 hours later), and a third cohort of 6 AGMs was treated with one intravenous dose of 20 mg/kg Valortim(R) when positive by ECL.
Results showed that 56% (10 of 18) of the Valortim(R)-treated animals survived while all saline-treated controls (3) succumbed to inhalational anthrax on or before the fifth day post-exposure. Extended time-to-death (days 6-9) was observed in 5 of the 8 Valortim(R)-treated animals that succumbed to inhalational anthrax.
An oral presentation entitled, "Valortim(R), an Anti-toxin Monoclonal Antibody, for the Treatment and Post-exposure Prophylaxis of Inhalation Anthrax," provided a summary of the Valortim(R) development program.
In the Phase I clinical study, 46 human volunteers were administered either a single dose of intravenous (IV) Valortim(R) (dose range 0.3 mg/kg-20 mg/kg) or intramuscular Valortim(R) (100mg). Valortim(R) was found to be safe and well-tolerated with no drug-related Grade 2-4 or serious adverse events reported. PK analysis demonstrated a half-life of approximately 26 days for IV administration.
Valortim(R) has been tested in both the New Zealand White (NZW) rabbit and non human primate models to evaluate its efficacy in the post-exposure prophylaxis and therapeutic settings.
In the post-exposure setting, Valortim(R) was dosed starting one hour after spore exposure. Valortim(R) protected >85% of both NZW rabbits and non human primates at doses as low as 1 mg/kg beginning one hour after exposure to spores.
In the therapeutic setting, Valortim(R) was dosed starting at fixed time points after spore exposure (24 or 48 hours in the NZW rabbit) or after first demonstrating antigenemia by a positive ECL assay (AGM). Valortim(R) protected 88% and 42% of NZW rabbits that initiated treatment at 24 and 48 hours after spore exposure, respectively. When AGMs were treated with Valortim(R) at the time of first positive ECL after spore exposure, 56% of the animals survived.
"We are very excited about the animal model data from the AGM study, which showed over 50% of Valortim(R)-treated animals survived inhalational anthrax as compared to no controls. This is especially compelling given that the toxin-releasing bacteria were present in the bloodstream at the time treatment was initiated. The AGM model, which we have been developing with the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) is believed to closely mimic the disease course of inhalational anthrax infection in humans. In this therapeutic model, treatment with Valortim(R) is begun only after anthrax toxin is first detected in the circulation. This model may provide an important improvement over existing therapeutic models for anthrax by precisely defining a standardized timing for therapeutic intervention," commented Mr. Wright.
Valortim(R) is a fully human antibody designed to protect against inhalation anthrax, the most lethal form of illness in humans caused by the Bacillus anthracis bacterium. The investigational antibody is designed to target a protein component known as the anthrax protective antigen of the lethal toxin complex produced by the bacterium. The anthrax protective antigen is believed to initiate the onset of the illness by attaching to cells in the infected person, and then is believed to facilitate the entry of additional destructive toxins into the cells. Valortim(R) is designed to target anthrax protective antigen and protect the cells from damage by the anthrax toxins.
Protexia(R) is a recombinant version of human butyrylcholinesterase (BChE), a naturally occurring protein found in minute quantities in blood (2 mg/liter). BChE functions as a natural bioscavenger, like a sponge, to absorb and degrade organophosphate poisons (e.g. nerve agents) before they cause neurological damage. Protexia(R) is being developed as a pre- and post-exposure therapy for casualties on the battlefield or civilian victims of nerve agent attacks. Nerve agents belong to a class of compounds known as organophosphate (OP) agents. OP nerve agents, such as sarin gas, soman, tabun or VX, enter the blood stream via inhalation or absorption through the skin. The nerve agents travel in the circulatory system to the brain and muscles causing the nerves to become over-stimulated which leads to massive convulsions and death in severe cases.
About PharmAthene, Inc.
PharmAthene was formed to meet the critical needs of the United States and its allies by developing and commercializing medical countermeasures against biological and chemical weapons. PharmAthene's lead product development programs include:
-- SparVax(TM) -- a second generation recombinant protective antigen (rPA) anthrax vaccine -- Third generation rPA anthrax vaccine -- Valortim(R) -- a fully human monoclonal antibody for the prevention and treatment of anthrax infection -- Protexia(R) -- a novel bioscavenger for the prevention and treatment of morbidity and mortality associated with exposure to chemical nerve agents -- RypVax(TM) -- a recombinant dual antigen vaccine for plague
For more information about PharmAthene, please visit http://www.pharmathene.com/.
Statement on Cautionary Factors
Except for the historical information presented herein, matters discussed may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words "potential"; "believe"; "anticipate"; "intend"; "plan"; "expect"; "estimate"; "could"; "may"; "should"; or similar statements are forward-looking statements. PharmAthene disclaims, however, any intent or obligation to update these forward-looking statements. Risks and uncertainties include risk associated with the reliability of the results of the studies relating to human safety and possible adverse effects resulting from the administration of the Company's product candidates, unexpected funding delays and/or reductions or elimination of U.S. government funding for one or more of the Company's development programs, the award of government contracts to our competitors, unforeseen safety issues, unexpected determinations that these product candidates prove not to be effective and/or capable of being marketed as products, as well as risks detailed from time to time in PharmAthene's Form 10-K under the caption "Risk Factors" and in its other reports filed with the U.S. Securities and Exchange Commission (the "SEC"). In particular, the studies described above involving Protexia(R) and Valortim(R) constitute non-clinical animal studies. Significant additional non-clinical animal studies, human clinical trials, and manufacturing development work remain to be done under both programs. At this point there can be no assurance that either of these product candidates will be shown to be safe and effective and approved by regulatory authorities for use in humans. Copies of PharmAthene's public disclosure filings are available from its investor relations department and our website under the investor relations tab at http://www.pharmathene.com/.
CONTACT: Stacey Jurchison of PharmAthene, Inc., +1-410-269-2610,[email protected]
Web site: http://www.pharmathene.com/