Superantigen antagonist

Atox Bio has developed a powerful antagonist to the family of bacterial superantigen toxins produced by Staphylococcus aureus and Streptococcus pyogenes. This is a particularly large and structurally divergent family of toxins and this diversity poses a complex medical problem calling for the development of a broad-spectrum superantigen antagonist. These superantigen antagonists have been found to modulate the Th1/Th2 immune balance.

The uniqueness of Atox Bio’s approach is in its focus on halting the "toxicity cascade" set off by superantigens even before the activation of T cells occurs.

Following is a schematic description of the mechanism of action of the superantigen antagonist:

Mechanism of action

Atox Bio scientists have gained a profound understanding of the mechanism of action of superantigens at the molecular level. Revealing the innate immune response’s novel strategy of subversion, they observed that structurally divergent superantigen toxins co-opt an additional host receptor, for use as their obligatory receptor. This insight led to the design of two distinct classes of superantigen antagonists. The discovery of novel target receptors for superantigens forms the basis of a platform technology for the generation of novel antagonist lead candidates. These antagonists act as immunomodulators that alter the Th1/Th2 balance. This constitutes a wholly new approach to the treatment of autoimmune diseases.

Product

Superantigen antagonists and immunomodulators are short peptides with potent activity.

Proof of principle and scientific recognition

Proof of principle for the superantigen toxin antagonist has been demonstrated in a mouse model of lethal toxic shock and in a pig model of superantigen-induced incapacitation. Antagonist efficacy in mice was reported in the prestigious medical journal Nature Medicine (2000). A description of the novel insight into superantigen mode of action, discovered by Atox Bio’s scientists, is being prepared for publication.

A novel pig incapacitation model that uses quantitative parameters developed by Atox Bio for incapacitation symptoms was accepted by the FDA as suitable for pre-clinical development.

The research was initially supported by the US Army and DARPA with US $6.5 million in grants.

The National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) is supporting Atox Bio's biodefense product development in collaboration with the Hebrew University of Jerusalem with a grant of US $5.6 million. NIH has defined the research as unique in the world.

This recognition and funding validates the scientific merit and therapeutic value of Atox Bio’s technology.