Botulinum Immune Globulin (BIG) – Therapeutic Product Candidate

Botulism is a frequently fatal disease caused by botulinum toxins produced by the bacterium Clostridium botulinum. Clostridium botulinum is widely distributed in soil and aquatic environments throughout the world. Botulinum bacteria produce seven distinct serotypes, each of which elicits a distinct antibody response. Naturally occurring outbreaks of botulism in humans have been reported from exposure to four of the seven serotypes: A, B, E and F. Botulism normally occurs when an individual consumes contaminated food containing botulinum toxin. Once consumed, the toxin rapidly attacks nerve cells, resulting in paralysis of peripheral muscles, including the muscles involved in respiration. Botulism can also be contracted if botulinum bacteria contaminate wounds or colonize in the intestine of infants, which is referred to as infant botulism.

Botulinum toxins are among the most potent and dangerous of potential biological weapons. Exposure to very small quantities of botulinum toxin can cause the rapid onset of life threatening paralytic disease syndrome. It has been estimated that a single gram of toxin evenly dispersed and inhaled could kill more than one million people.

Product Candidate Description

We are developing our BIG candidate in collaboration with the Health Protection Agency as an intravenous therapeutic for treatment of symptomatic botulinum exposure. Because of the rapid onset of symptoms following infection with botulinum toxin, prophylactic vaccines, which take several weeks to create an effective protective immune response, are not useful as post-exposure treatments for botulism. In addition, antibiotics are not effective post-exposure treatments since they work by killing the botulinum bacteria that produce the toxin, but do not act directly against the botulinum toxin. We believe that an intravenous botulinum immune globulin (BIG) has the potential to protect against the effects of botulinum toxin.

Market Opportunity And Current Treatment

The only current recommended therapy for exposure to botulism consists of passive immunization with an immune globulin derived from equine plasma. The components of a previously approved trivalent equine immune globulin that contained antibodies against botulinum toxin types A, B, and E have been reformulated into an approved bivalent product and an investigational monovalent product. In June 2006, HHS awarded a five-year development and supply contract to another company for the supply of 200,000 doses of a heptavalent botulinum immune globulin derived from equine plasma for the strategic national stockpile. We believe that equine immune globulin products are subject to important shortcomings, including possible limited efficacy and side effects associated with the use of equine plasma in manufacturing.

Development Status

Our plan is to develop our BIG candidate as a human immune globulin product, which will be derived from antibodies produced by healthy donors immunized with a botulinum vaccine. As the first step in our development program, we are initiating production of a bivalent botulinum toxoid vaccine using botulinum serotype B derived from the starting material for the pentavalent vaccine developed by the Michigan Department of Public Health and serotype A from HPA. We are designing this botulinum toxoid vaccine to be administered by injection with an alum adjuvant. We anticipate that several doses will be needed to elicit a strong immune response. We are performing development activities at existing HPA facilities, which we expect may expedite production of clinical material for the vaccine. HPA is also providing us with process development and specialized manufacturing capabilities for the vaccine.