Research Programs
The first fusion toxins were described in the literature in 1986.  Since then, a large body of work has been published on fusion toxins based on a variety of bacterial toxins, including diphtheria, pseudomonas, and shigella, as well as plant toxins, including ricin, gelonin, and bouganin.  For the most part, clinical trials with fusion toxins have focused on hematologic malignancies, largely because these have been considered to be the most accessible to biologics.  While there have been many reports of substantial efficacy, progress toward market approval has been restrained by two overriding limitations, immunogenicity and safety.  Nearly without exception, both bacteria- and plant-derived toxins have been found, not surprisingly, to elicit robust immune responses, which typically limit the potential for repeat dosing.

Ontak® (denileukin diftitox), a truncated form of diphtheria toxin fused to interleukin-2 (IL-2), was approved in 1999 for the treatment of CD25+ cutaneous T cell lymphoma (CTCL).  Whereas 49% of these CTCL patients responded to Ontak® treatment in a Phase III clinical trial, we are optimistic that partial responses may become complete responses and that transient responses will be more sustained when deimmunization allows for extension of the treatment series.

Future plans include replacement of IL2 with antibody fragments and other ligands to target this valuable toxin to other cancers.  Partners with highly specific ligands or cancer antibodies are being actively considered.