Eli Lilly and Company and Isis Pharmaceuticals, Inc. announced LY2181308, a second-generation antisense drug that targets survivin, inhibited tumour growth in animal models. Antitumour activity was associated with significant reduction of survivin expression in tumours, evidence that the drug was working through an antisense mechanism. These data were presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. Survivin is a molecule that promotes cell survival. These cells would otherwise undergo programmed cell death, a natural process in the cell life cycle. Survivin is expressed in a vast majority of cancers, but not in normal tissue.

"These are among the first reported data to demonstrate antitumour activity in vivo using a drug that specifically inhibits survivin expression. As an antisense drug, LY2181308 binds to survivin RNA, enabling it to inhibit the production of a target considered undruggable by traditional protein-binding approaches," said Dr. Richard Gaynor, vice president for cancer research and clinical investigation at Lilly. "The over expression of survivin in a wide variety of tumours makes it an exciting target for drug development. We look forward to the advancement of this novel compound for the treatment of cancer."

"These results broaden the extensive preclinical package Isis and Lilly have developed for LY2181308 by demonstrating potent antitumour activity in animals. We are enthusiastic about this survivin antisense drug, the first product to be selected for clinical development from our broad-antisense drug discovery collaboration with Lilly. We believe antisense drugs have the potential to benefit patients with cancer and numerous other diseases," said Frank Bennett, vice president antisense research for Isis.

LY2181308 demonstrated consistent activity in both human xenograft tumour models and multiple cancer cell lines derived from the lung, colon, breast, prostate, ovary, cervix, skin and brain, according to data presented by Dr Bharvin KR Patel, research scientist at Lilly, in a poster entitled "Antisense Inhibition of Survivin Expression as a Cancer Therapeutic." Inhibition of survivin by LY2181308 produced the following results:

Inhibition of tumour growth as demonstrated in animal models Antitumour activity associated with selective inhibition of survivin protein expression and with no effects on other anti-apoptotic proteins Induction of programmed cell death as evidenced by: multinucleated cells in both animal models and cell lines induction of Cyclin B1 expression in the tumours in animal models cell cycle arrest at G2/M phase of the cell division cycle, and concentration-dependent increase in caspase-3 activity in tumour cells

Lilly licensed LY2181308 from Isis as a part of the cancer drug discovery collaboration the companies previously initiated. The oncology relationship builds on a broad, ongoing strategic alliance established by Isis and Lilly to discover antisense drugs in the areas of inflammatory and metabolic diseases.