Antisense - Antisense Product Pipeline

ANTISENSE THERAPEUTICS R&D PIPELINE

ATL1102 subcutaneous injection, for Multiple Sclerosis
ATL1102 is a second generation antisense inhibitor of CD49d, a subunit of VLA-4 (Very Late Antigen-4), and is currently in Phase IIa clinical trials as a treatment for MS. In inflammation, white blood cells (leukocytes) move out of the bloodstream into the inflamed tissue, for example, the CNS in MS, and the lung airways in asthma. The inhibition of VLA-4 may prevent white blood cells from entering sites of inflammation, thereby halting progression of the disease. Antisense inhibition of VLA-4 has demonstrated positive effects in a number of animal models of inflammatory disease including MS.

ATL1103 subcutaneous injection, for Acromegaly and Vision disorders (Preclinical Development)
ATL1103 is a second generation antisense drug designed to block growth hormone receptor (GHr) expression thereby reducing levels of the hormone insulin-like growth factor-I (IGF-I) in the blood and is a potential treatment for diseases associated with excessive growth hormone action. These diseases include acromegaly, an abnormal growth disorder of organs, face, hands and feet, and diabetic retinopathy, a common disease of the eye and a major cause of blindness.

ATL1102 inhaled, for asthma (Preclinical Research)
We have obtained encouraging pharmacological benefit with an inhaled VLA-4 antisense drug in one of the most widely used experimental models of asthma, the ovalbumin-challenged mouse model. This suggests that local inhibition of VLA-4 expression in the lung may provide benefits such as reducing the activation of lung inflammatory cells, in addition to the known ability of VLA-4 inhibitors to prevent white blood cells from entering sites of inflammation. Inhaled antisense drugs appear to be active at very low inhaled doses in these studies, making antisense drugs an attractive option in the search for effective and safe asthma medicines.

ATL1101 for Prostate Cancer
ATL1101 is an antisense inhibitor of IGF-Ir which has shown potent activity in laboratory studies, including in human cancer cells. IGF-Ir is one of the best known of a family of cell signaling molecules that are referred to as "anti-apoptotic". These molecules prolong cell survival by inhibiting programmed cell death (apoptosis). The connection between IGF-Ir activity and prostate cell tumorigenicity has been studied for many years. Inhibition of cell survival molecules like IGF-Ir can render tumour cells more susceptible to cell death with cytotoxic (cell death inducing) drugs. Similar "chemosensitiser" therapeutic approaches targeting the IGF-Ir are under investigation in several large pharmaceutical companies, lending support to our own antisense-based strategy against the same target.

Prostate cancer is the second most frequently diagnosed cancer in men after skin cancer. It is estimated there will be 218,890 new cases diagnosed in the U.S. this year. Around 1 in 6 men will develop prostate cancer, a third to a half of whom will recur after local treatment and risk progression to metastatic prostate cancer. Metastatic disease invariably progresses to hormone refractory prostate cancer (HRPC) if given enough time. Treatment options are limited for HRPC, and prognosis is poor. There is a pressing need for the development of new treatments.