Inflammation Franchise

Background

Inflammation is a response of the body to injury, disease or irritation, often characterised by redness, swelling and pain. Inflammation plays a key role in many human diseases such as rheumatoid arthritis (RA), psoriasis, ankylosing spondylitis and inflammatory bowel disease. The commercial market for effective anti-inflammatory treatments is large, and is estimated to reach in excess of US$20 billion by 2012.

Tumour Necrosis Factor alpha (TNF) is a protein which is known to play a key role in the development of certain inflammatory diseases and is the target of Arana’s lead anti-inflammatory compound ART621. TNF has proved to be a valuable target because elevations in its levels trigger a cascade effect, causing the release of many different inflammatory molecules. Blocking the effects of TNF can block the cascade effects associated with inflammatory disease.

ART621 - a Phase II asset

ART621 is a new type of therapeutic protein which incorporates a domain antibody (dAb). Domain antibodies exhibit the target binding properties of a full-sized antibody, but are considerably smaller and may have advantages in relation to production, immunogenicity and penetration of diseased joints and tissues.

A number of anti-TNF products (Humira®, Remicade®, Enbrel® and Cimzia®) are currently marketed for the treatmen0t of RA. Unlike earlier treatments, such as aspirin, that deal with the signs and symptoms, these anti-TNF products act to prevent against further progression of the disease.

Alternative antibody-based treatments are still needed because some patients have stopped responding to a particular anti-TNF antibody after prolonged use, yet respond well when treated with an alternative anti-TNF product.

In animal models of RA, ART621 matched the performance of a leading marketed anti-TNF antibody and also displayed favourable properties. It has successfully progressed through Phase I clinical trials and a Phase II trial in psoriasis is currently in progress. Recruitment for this study was completed in August 2008, and results are expected to be reported in the first quarter of 2009.

In early November ART621 successfully passed review of its RA Investigational New Drug (IND) application, and is proceeding with its Phase II study in RA.

ART621 Blocking TNF

PMX53 - in pre-clinical development

Complement 5a (C5a) is a naturally occurring protein that is implicated in many human inflammatory diseases. PMX53 is a C5a inhibitor. Arana has developed and tested several formulations of PMX53 in animal models of age-related macular degeneration (AMD), psoriasis and osteoarthritis. Arana has selected AMD as the lead clinical indication for PMX53. A clinical trial is expected to commence in the first half of 2009 subject to the successful completion of ongoing pre-clinical dose-ranging studies. Data from a long term pre-clinical osteoarthritis study are also expected to be available in early 2009.

ART123 - a new product in the pipeline

Arana has recently developed a new antibody candidate ART123, also targeting inflammatory diseases. In September 2008, Arana announced the new antibody targeting the interleukin 12/23 (IL12/23) pathway. The IL12/23 pathway is important in human inflammatory disease and has been clinically validated in psoriasis.

ART123 was produced using Arana’s proprietary antibody engineering technologies. Patents have been filed around the novel mechanism of action of ART123, which has demonstrated efficacy in a pre-clinical psoriasis model. Pre-clinical safety studies are expected to commence in 2010.