Botulinum Immune Globulin (BIG) – Therapeutic Product Candidate

• Disease Overview
• Product Candidate Description
• Market Opportunity  Current Treatment

Disease Overview

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 two vaccine candidates to protect against botulinum illness caused by botulinum serotypes A, B and E. The first, in collaboration with the United Kingdom’s Health Protection Agency (HPA), is a recombinant protein subunit trivalent vaccine based on a fragment of the botulinum toxin that we have selected as an antigen because we believe it to be non-toxic and immunogenic. Our second vaccine candidate is a botulinum toxoid vaccine that includes a combination of up to three botulinum serotypes A, B and E. We are developing this product using our proprietary botulinum serotypes B and E and serotype A from HPA.

Market Opportunity 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.