SMALL MOLECULE PROGRAM

Dendreon has a small molecule program in development. Small molecules are a diverse group of natural and synthetic substances that generally have a low molecular weight and are either isolated from natural sources such as plants, fungi or microbes or synthesized by organic chemistry. Most conventional pharmaceuticals, such as aspirin, and chemotherapeutics, are small molecules.

TRPM8 (also known as TRPP8), was identified through in-house efforts. It is a calcium ion channel that is triggered by cold temperatures, menthol, and other small molecule agonists. TRPM8 belongs to the melastatin subfamily of TRP proteins. Calcium ions mediate key cellular functions, and activation of TRPM8 channels leads to programmed cell death (apoptosis) in TRPM8-expressing cells.

In normal human tissues, TRPM8 is expressed predominantly in the prostate, ProstateA gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.Close a gland in the male reproductive system. It is over-expressed in prostate hyperplasia and multiple types of cancer, including prostate cancer, breast cancer, colon cancer and lung cancer. Dendreon has synthesized small molecule agonists, including D3263, which activate the TRPM8 ion channel and induce cell death (apoptosis). The small molecule agonists are orally bioavailable, and in December 2008, an Investigational New Drug (IND) application was filed with the FDA. In 2009, we commenced our Phase 1 clinical trial to evaluate D-3263 HCl in patients with solid tumors. The trial is currently ongoing.