Inflammatory Disease

The broad applicability of our antisense technology allows us to create promising drugs in a variety of disease areas, many of which are underserved with current treatment options. For instance, our partner, Altair Therapeutics, recently presented encouraging Phase 1 data from our first inhaled antisense drug, AIR645, in patients with mild asthma. AIR645 is now being evaluated in a Phase 2a study and, if effective, could offer a new non-steroidal, anti-inflammatory treatment for patients with asthma. AIR645 is our first inhaled antisense drug to enter human studies and is an example of the different routes of administration to optimize distribution that we can utilize.

• Alicaforsen (Ulcerative Colitis, Pouchitis)
• AIR645 (Asthma)
• ATL1102 (Multiple Sclerosis)

Alicaforsen

Alicaforsen, now under license to Atlantic Pharmaceuticals Limited, is an antisense drug that targets intercellular adhesion molecule 1, or ICAM-1. Over-expression of ICAM-1 occurs in a wide variety of inflammatory disorders, including ulcerative colitis and pouchitis. Ulcerative colitis is an inflammatory bowel disease of the colon, a part of the large intestine, and pouchitis is an inflammation of the surgically constructed internal pouch created in ulcerative colitis patients who have had their diseased colons removed. In 2007, we licensed alicaforsen to Atlantic Pharmaceuticals for pouchitis, ulcerative colitis and other inflammatory diseases. The FDA and European Medicines Agency have since granted alicaforsen Orphan Drug Designation for the treatment of pouchitis in the US and Europe respectively.

AIR645

AIR645 is an inhaled second generation antisense drug that targets the alpha subunit of the interleukin 4 receptor, or IL-4R-alpha, which inhibits interleukin 4, or IL-4, and interleukin 13, or IL-13, signaling. IL-4 and IL-13 are two important cytokines in asthma, which regulate inflammation, mucus overproduction and airway hyper-responsiveness. In 2007 we licensed AIR645 to Altair, a company focused on the discovery, development and commercialization of novel therapeutics to treat human respiratory diseases. In preclinical studies, we showed that inhibiting IL-4R-alpha with an antisense compound potently reduced target RNA and protein levels. Inhibiting IL-4R also demonstrated pharmacologic activity in mouse models of asthma that included reducing lung cytokine production, inflammation, and airway hyper-responsiveness. In addition, these studies showed that, when delivered by inhalation, AIR645 rapidly distributed to the airways and achieved therapeutic drug concentrations in multiple cell types with little systemic exposure.

In September 2009, Altair reported the successful completion of a Phase 1 study on AIR645 evaluating the safety and tolerability of AIR645 in healthy volunteers. Researchers presented the Phase 1 results at the European Respiratory Society Annual Congress that showed treatment with AIR645 was safe and well tolerated in subjects. In November 2009, Altair initiated a Phase 2 study of AIR645 in patients with mild asthma.

ATL1102

ATL1102 is an antisense inhibitor of CD49d, which is a subunit of Very Late Antigen-4, or VLA-4. Studies in animal models have demonstrated that inhibiting VLA-4 positively affects a number of inflammatory diseases, including multiple sclerosis, or MS.

We licensed ATL1102 to Antisense Therapeutics Limited in December 2001. In 2008, ATL reported Phase 2a results of ATL1102 showing significantly reduced disease activity in patients with relapsing remitting MS.