Annexin and its Use to Treat Inflammatory Disorders

Background:

Sepsis is a complex clinical syndrome resulting from a harmful host immune response to infection characterized by the production of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, which has been shown to be one of the main mediators of cardiovascular dysfunction. Cardiovascular dysfunction is common in patients with sepsis and contributes to the development of multi-organ failure associated with an extremely high mortality of ~50%. Sepsis is one of the leading causes of death globally and yet there are currently no approved therapeutic products on the market. Furthermore, to date none of the very few alternatives in clinical development have demonstrated substantial promise in advanced trials. The failure of many drugs for sepsis may be due to a single mode of action for a complex syndrome. New drugs with minimal side-effects that are able to intervene at multiple points in the sepsis cascade to decrease mortality are desperately needed.

Technology Overview:

Annexin A5 is a multi-faceted protein with potent anti-inflammatory, anti-apoptotic, and anti-coagulant effects. Lawson scientists have discovered that it significantly reduces myocardial TNF-α production and IL1-β production during sepsis resulting in significant improvement in cardiac function and survival (>40%) in clinically relevant animal models of sepsis. They have also discovered a novel interaction of annexin A5 with Toll-like receptor-4 (TLR4) that competes with bacterial endotoxin for binding to TLR4 to initiate sepsis..

Benefits:

• Significantly reduces myocardial TNF-α and IL1-β production during sepsis.
• Interacts directly with TLR4 receptors and inhibits TLR4-mediated sepsis initiation/escalation by bacterial endotoxin.
• A multi-faceted therapeutic with potent anti-inflammatory, anti-apoptotic, and anti-coagulant effects.
• Anti-coagulant activity is mild and not expected to generate bleeding related side-effects.
• Annexin A5 has been used in humans for imaging studies with no reported adverse side-effects.

Applications:

• A novel prophylactic and therapeutic treatment for sepsis that improves cardiac function and reduces mortality.
• May improve the function of other organs during sepsis and have therapeutic potential for other inflammatory conditions.

Opportunity

Lawson Health Research Institute are seeking a clinical development partner.

For further information see: Arnold et al. 2014. Recombintant human annexin A5 inhibits proinflammatory response and improves cardiac function and survival in mice with endotoxemia. Crit Care Med. 42(1): e32‑41.

Seeking

Licensing, Development Partner, Commercial Partner

IP Status

CA 2,740,557

US 9,192,649

JP 5590621

EP 09820159.3