Technology Platform

The Inimex Invention - Drugs to fight infection and suppress inflammation

A major disincentive to pharmaceutical exploitation of the innate system has been the knowledge that prolonged or excessive expression of certain inflammatory mediators in response to infection can lead to significant tissue damage.

For example, excessive release of pro-inflammatory cytokines such as tumour necrosis factor-a (TNF-a) can lead to an inflammatory cascade that - if left unchecked - can result in sepsis, a potentially lethal condition. Furthermore, most antibiotics stimulate the release of bacterial components and thus contribute to the risk of damaging inflammation or sepsis. As a result, administration of TLR agonists has been limited to circumstances where stimulation of inflammation can be contained or managed (through localised or low dosing, e.g., vaccine adjuvant or allergy applications, or in specialized circumstances, e.g., oncology / antiviral applications).

The groundbreaking discovery made in the laboratories of Professors Bob Hancock and Brett Finlay at the University of British Columbia was that clearance of an infection by the innate immune system could be achieved without triggering inflammation. They found that certain short peptides, including endogenous peptides produced by neutrophils as well as novel synthetic derivatives engineered to lack direct antibacterial activity, were able to clear Gram positive or Gram negative bacterial infections in mice. Inimex peptides are able to clear lung infections with S. pneumoniae, the most common cause of bacterial pneumonia. In this pneumonia model Inimex compounds demonstrate activity comparable to azithromycin (Pfizer's Zithromax®), one of the leading antibiotics prescribed for pneumonia.

Genomics protein and cellular assessments confirm that Inimex peptides act on a cytoplasmic protein target to cause increases in gene products associated with infection-clearing aspects of innate immunity without causing up-regulation of pro-inflammatory cytokines such as TNF-a. A peer-reviewed publication in Nature Biotechnology reports many of these findings from studies using a prototype proprietary peptide IDR-1. These data, showing that innate immunity can be selectively up-regulated without causing local inflammation, are in sharp contrast to observations made using TLR agonists which rely upon stimulation of inflammatory mediators to achieve therapeutic impact.

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