Recombinant Bivalent Botulinum (rBOT) Vaccine – Product Candidate

• Disease Overview
• Product Candidate Description
• Market Opportunity and 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 a recombinant protein subunit bivalent botulinum vaccine (rBot) for protection against botulinum serotypes A and B in collaboration with the Health Protection Agency (HPA). We are designing our vaccine candidate to be administered by intramuscular injection with an alum adjuvant in a three dose regimen. Our recombinant vaccine candidate is 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. We are producing this recombinant antigen in an E. coli expression system. We believe that our technology will allow us to develop a stable product with possible cross-protection against a range of toxin subtypes and ease of formulation into a multivalent vaccine.

Market Opportunity and Current Treatment

The Michigan Department of Public Health first developed a pentavalent botulinum toxoid vaccine in the late 1960s and began manufacturing the pentavalent vaccine for use under an IND in 1969. Since 1989, the CDC and the DoD have distributed the pentavalent botulinum toxoid vaccine under this IND for vaccination of at risk laboratory workers and military personnel as an adjunct to other measures of protection. In connection with our acquisition of assets from the Michigan Biologic Products Institute in 1998, we acquired rights to the pentavalent vaccine, know-how relating to the development of the pentavalent vaccine and rights to a master botulinum cell bank, which provides starting materials for the pentavalent vaccine. After more than 15 years of use, the supplies of pentavalent botulinum toxoid vaccine are dwindling and in need of replacement. In August 2003, HHS issued a pre-solicitation notice for the acquisition of up to ten million doses of a recombinant trivalent botulinum vaccine, which would address botulinum serotypes A, B and E. HHS was seeking a trivalent vaccine because botulinum serotype F is more difficult to produce under cGMP conditions and does not appear to represent the same level of threat as other serotypes of botulinum neurotoxin. We also believe that botulinum serotype E does not represent the same level of threat as serotypes A and B. Botulinum serotypes A and B are responsible for approximately 85% of all cases of botulism. In November 1997, DoD, through its Joint Vaccine Acquisition Program, awarded a contract to another company for the development of various biodefense vaccines, including a botulinum vaccine. In April 2005, DoD provided additional funding to that company for the continued development of a recombinant bivalent botulinum vaccine for protection against botulinum serotypes A and B.