Protexia™ - A Bioscavenger

Taking advantage of Nexia's expertise in the production of recombinant proteins in the milk of transgenic goats, we are proud to announce our latest biopharmaceutical program - Protexia™, formerly known as our NEX-91 program.

Protexia™ is Nexia's recombinant version of butyrylchoinesterase (BChE), a naturally occurring protein found in minute quantities in blood. Studies in the literature have used plasma derived BChE in animal studies and have shown that increasing BChE concentrations in the blood protect laboratory animals from the toxic effects of nerve agents. However, due to the inability to produce commercial volumes of BChE to date, it has been impossible to use BChE as a protective agent. BChE functions in the blood as a bioscavenger, like a sponge, to absorb the nerve agent before it can do its damage. Protexia™ will be developed to treat and prevent the toxic effects of nerve agents and other dangerous compounds.

OP (Nerve) Agents and BChE

Nerve agents belong to a class of compounds known as organophosphorous (OP) agents. They were first developed in the 1930's to use as insecticides. Their potency was recognized during World War II, and they were developed as nerve agents to use in chemical warfare. In recent history, terrorists have deployed nerve agents as a weapon of mass destruction – one of the most tragic incident occurred in 1995 when sarin gas was released in the Tokyo subway system, injuring thousands and killing 12.

Nerve or OP agents, such as sarin gas 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 leading to massive convulsions and death in severe cases.

BChE, as a bioscavenger, binds to the components of the nerve agents and neutralizes them before they can reach the brain. BChE is found naturally in human blood to defend the body from certain food toxins, but, unfortunately, these levels are insufficient to counteract the effects of a chemical weapon attack.

BChE has been isolated in small quantities from human blood and shown to protect animals from lethal doses of nerve agents with little or no side effects observed. It is impractical and expensive, however, to isolate enough BChE from blood to protect a large number of people. Recombinant technologies to date have not solved this problem despite significant research efforts to produce large quantities of BChE. We believe that Nexia's transgenic technology may provide a way to produce large enough quantities of this enzyme to allow broad commercialization.

Protexia™ Fills a Market Need

Initially, the primary market for Protexia™ would be the US military. There are 1.4 million personnel in the US Department of Defense. Given the significant resources devoted to development of bioscavengers in the US, we expect to fill a defined need identified by the largest military in the world. We also believe other militaries, particularly those of Canada and other NATO countries, would be likely customers for Protexia™.

Additionally, civilian first-responders such as firefighters, police and emergency crews, may also benefit from having stockpiles of Protexia™.

Work to Date

Nexia has been working on Protexia™ since 2001 and during this time has begun preliminary development of Protexia™ in its proprietary MAC-T (Mammary Alveolar Cells with large-T antigen) cell line and in transgenic mice and goats. Nexia expects to continue this work with the Defence Research and Development Canada (DRDC)-Suffield, to initiate pre-clinical evaluation studies in relevant in vitro and in vivo specimens.

References

Lenz, David E., Broomfield, Clarence, Maxwell, Donald, Cerasoli, Douglas. Nerve agent bioscavengers: Protection against high and low dose organophosphorus exposure. In Chemical Warfare Agents: Toxicity at Low Levels (eds S. Somani and J. Romano, Jr.). CRC Press: Florida, 2001.

Broomfield, CA, Maxwell, DM, Solana, RP, Castro, CA, Finger, AV and Lenz, DE, "Protection of butyrylcholinesterase against organophosphorous poinsoning in non-human primates," J Pharmacol and Exp Therapeut, Vol. 259(2), pg 633, 1991.

Wolfe, AD, Blick, DW, Murphy, MR, Miller, SA, Gentry, MK, Hartgraves, SL and Doctor, BP, "Use of cholinesterases as pretreatment drugs for the protection of rhesus monkeys against soman toxicity," Toxicol. Appl Pharmacol., Vol. 117, pg. 189, 1992.

Raveh, L, Grauer, E, Grunwald, J, Cohen, E and Ashani, Y, "The Stoichiometry of Protection against Soman and VX Toxicity in Monkeys Pretreated with Human Butyrylcholinesterase," Toxicol. Appl Pharmacol., Vol. 145, pg. 43, 1997.

Cascio, C, Comite, C, Ghiara, M, Lanza, G and Ponchione, A, "The use of serum cholinesterase in severe phosphorus poisoning," Minerva Anestesiol (Italian) Vol. 54, pg 337, 1998.

Dunn, MA, Hackley, BE and Sidell, FR, "Pretreatment for nerve agent exposure," in Textbook of Military Medicine, Chapter 6 "Medical Aspects Of Chemical And Biological Warfare," 1997.

Broomfield, Clarence A., Anderson, Robert, LaDu, Bert N., Josse, Denis, Masson, P., "Hydrolysis of VX by Human Paraoxonase" Manuscript from Army Science Conference in December 2002 in Florida – www.asc2002.com/sessionD.htm (manuscript # DO-02)

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