Exelixis Reports Positive Clinical Pharmacodynamics Data for PI3K/mTOR Inhibitor XL7...( Robust Pathway Inhibition in Tumor a...),Health

Robust Pathway Inhibition in Tumor and Surrogate Tissues at Well-Tolerated

Doses

CHICAGO, May 31 /PRNewswire-FirstCall/ -- Exelixis, Inc. (Nasdaq: EXEL) reported interim data from a phase 1 dose-escalation trial of XL765, a novel small molecule inhibitor of phosphoinositide-3 kinase (PI3K) and mTOR, which are implicated in tumor cell proliferation, survival, and resistance to chemotherapy and radiotherapy. The trial is being carried out in patients with metastatic or unresectable solid tumors for which known effective measures do not exist or are no longer effective. Kyriakos Papadopoulos, MD, Clinical Investigator at South Texas Accelerated Research Therapeutics (START) and a lead investigator in the trial, presented the data in the PI-3 Kinase/mTOR Directed Agents oral abstract session (Abstract #3510) at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO).

There were 19 patients available for safety, pharmacokinetic, and tumor response analyses as of the May 1, 2008 cutoff. Results from pharmacodynamics analyses indicate that XL765 inhibits the PI3K/mTOR pathway in patients at well-tolerated doses. Reductions of 80-90% in the phosphorylation of pathway components including AKT, 4EBP1, and S6, and a reduction of 54% in cell proliferation (as assessed by Ki67 staining) were observed in tumor tissue from a patient with chondrosarcoma at the 60 mg twice-a-day (BID) dose level. Reductions in the phosphorylation of these pathway components were also observed at this dose level in surrogate patient tissues, including hair bulbs, skin, and peripheral blood cells. The pattern of inhibition of protein phosphorylation observed in these tissues is consistent with observations
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