XToll® - Innate Immune Modulation Technology

In 2001, extended preclinical studies at the University of Queensland concluded that a heat shock protein identified as chaperonin10 played a key role in down-regulating the innate immune response in patients during pregnancy. Further research suggested that chaperonin10 appeared to intercede at a very early stage of the inflammatory process to prevent the over-expression of inflammatory cytokines.

Chaperonin 10 is a naturally occurring protein present in all cells that, in conjunction with chaperonin 60, performs the essential housekeeping role of protein folding, i.e. it helps proteins develop into exactly the
right shape required for them to work effectively. CBio has demonstrated that recombinant chaperonin 10 (Cpn10, or XToll®) has an immunomodulatory function in addition to this well-established protein folding activity.

CBio has completed Phase I studies with both intravenous and subcutaneous administration, three intravenous dosing Phase II clinical trials in RA, psoriasis and multiple sclerosis, and one subcutaneous dosing trial in RA.

Data generated from the intravenous dosing Phase IIa rheumatoid arthritis clinical trial was accepted for publication in international medical journal The Lancet in September 2006 (Vanags et al, Lancet 2006; 368: 855-63). Findings through peer-review were that XToll® showed evidence of clinical effect in rheumatoid arthritis patients with well-established disease, while being well tolerated.

A similar paper recognising the therapeutic benefits in psoriasis was published in the Archives of Dermatology in May 200 (Williams et al, Arch Dermatol 2008; 144: 683-685); while multiple sclerosis data has been published in Multiple Sclerosis journal (Broadley et al. Multiple Sclerosis 2009, 15: 329-336).

In May 2008, CBio commenced a Phase IIa placebo-controlled clinical trial to assess the efficacy and safety of XToll® administered as twice weekly subcutaneous injections in patients with rheumatoid arthritis. The trial was conducted at sites throughout Australia and New Zealand, and Central and Eastern Europe. The trial completed in April 2011 and the final report was received in October 2011. Details of trial can be found at the Australia New Zealand Clinical Trials Registry.