EXELIXIS REPORTS XL647 CLINICAL DATA AT AACR-NCI-EORTC CONFERENCE
Updated phase 2 data continue to show encouraging anti-tumor activity in non-small cell lung cancer; Phase 1 data demonstrate tolerability of daily XL647 administration
San Francisco, CA – October 24, 2007 – Exelixis today reported updated data from a phase 2 study of XL647, an inhibitor of EGFR, HER2 and VEGFR kinases, in previously untreated, clinically selected non-small cell lung cancer (NSCLC) patients. The data continue to show encouraging anti-tumor activity for XL647 administered on an intermittent schedule. Additionally, XL647 was generally well tolerated and showed pharmacodynamic target modulation in an ongoing phase 1 study evaluating daily dosing in patients with advanced solid tumors. The data were presented in two posters at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, which is being held October 22-26, 2007 in San Francisco.
Consistent with data from the phase 2 study reported in September 2007 at the 12th International Association for the Study of Lung Cancer World Conference on Lung Cancer, 68% of the 34 patients evaluable for tumor response had clinical benefit: 10 patients had partial responses (eight confirmed, two not yet confirmed), and 13 patients had stable disease as their best response. All seven patients with activating EGFR mutations experienced tumor shrinkage (six PRs and one SD), and three patients with wild type EGFR achieved partial responses (Abstract #B124). XL647 was generally well tolerated in this patient population.
Additionally, data from a phase 1 dose-escalation study evaluating daily dosing of XL647 were presented (Abstract #B242). As of August 8, 2007, this study had enrolled 26 patients with a variety of advanced solid tumors. 11 of 21 patients assessable for tumor response receiving doses of XL647 ranging from 75 to 300 mg achieved stable disease for at least three months. The XL647 exposure with daily dosing at the maximum tolerated dose (MTD) (300 mg) in this study was approximately twofold higher over a 28-day cycle compared to the exposure observed previously at the MTD (350 mg) for the intermittent dosing regimen. XL647 was generally well tolerated and related Grade 3 adverse events were infrequent. No Grade 3 or greater skin rash was reported in this study. Pharmacodynamic analyses were conducted in plasma samples and eyebrow hair follicles. Biomarker changes consistent with EGFR inhibition were observed in eyebrow hair follicles following XL647 treatment.
“The phase 2 data continue to show encouraging anti-tumor activity for XL647 given on an intermittent schedule in previously untreated clinically selected NSCLC patients. Additionally, phase 1 data suggest that XL647 dosed daily at 300 mg is well tolerated and provides approximately twofold higher drug exposure over a 28-day cycle compared to intermittent dosing,†said George A. Scangos, Ph.D., president and chief executive officer of Exelixis. “We are pleased to continue to see evidence of good tolerability and no Grade 3 rash with XL647, and believe that a daily dosing strategy may have the potential to further enhance the anti-tumor activity in NSCLC.â€
The most common treatment-related adverse events (AEs) were Grade 1 and 2 diarrhea and dysgeusia, fatigue, rash, and clinically asymptomatic QTc prolongation. In phase 1, a total of ten serious AEs were reported in six patients; of these events, two were considered possibly or probably related to XL647. These two drug-related events of Grade 3 pneumonitis and Grade 4 myocardial infarction occurred in the same patient. The cohort was expanded, and no further dose-limiting toxicities (DLTs) were observed. Two events of clinically asymptomatic Grade 3 QTc prolongation occurred in two of four patients enrolled at the 350 mg dose when read by machine. On manual re-read these events were determined to be Grade 2. The dose of 300 mg was declared to be the MTD when administered daily.
The adverse event profile in phase 2 was consistent with phase 1: the most common adverse events were Grade 1 and 2 diarrhea, rash, fatigue, and nausea. Clinically asymptomatic QTc prolongation was also observed.
About the Phase 2 Trial of XL647 as First-Line Therapy
This open-label phase 2 trial is ongoing in previously untreated patients with stage IIIB or IV NSCLC who have adenocarcinoma histology and meet one of the following three criteria: Asian descent, female gender, or no or minimal smoking history. XL647 is administered orally at a dose of 350 mg on Days 1-5 of repeated 14-day cycles. The trial is designed to enrich for patients with activating mutations in the EGF receptor (EGFR) which have been associated with improved sensitivity to other EGFR inhibitors. Based on the selection criteria, Exelixis anticipates that approximately 30 percent of subjects in the trial will have activating EGFR mutations. This design should allow the accumulation of data for patients with and without EGFR mutations, helping to identify those patients most likely to benefit from treatment with XL647.
About XL647
XL647 is a potent inhibitor of receptor tyrosine kinases (RTKs) that are implicated in driving tumor cell proliferation and tumor vascularization (blood vessel formation). XL647 inhibits EGFR, HER2 and VEGFR2. The compound has been optimized for high potency and oral bioavailability, demonstrates excellent activity in target-specific cellular functional assays, and has shown sustained inhibition of target RTKs in vivo in preclinical models following a single oral dose. Two phase 2 trials in patients with NSCLC are ongoing.
About Exelixis
Exelixis, Inc. is a development-stage biotechnology company dedicated to the discovery and development of novel small molecule therapeutics for the treatment of cancer and other serious diseases. The company is leveraging its fully integrated drug discovery platform to fuel the growth of its development pipeline, which is primarily focused on cancer. Currently, Exelixis' broad product pipeline includes investigational compounds in phase 2 and phase 1 clinical development for cancer and renal disease. Exelixis has established strategic corporate alliances with major pharmaceutical and biotechnology companies, including GlaxoSmithKline, Bristol-Myers Squibb Company, Genentech, Wyeth Pharmaceuticals and Daiichi-Sankyo. For more information, please visit the company's web site at http://www.exelixis.com.
Forward-Looking Statements
This press release contains forward-looking statements, including without limitation statements related to the future development and potential efficacy of XL647. Words such as "believe," "suggest," “may,†“anticipates,†“should,†“will†and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Exelixis' current expectations. Forward-looking statements involve risks and uncertainties. Exelixis' actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, the lengthy, costly and uncertain process of clinical testing of XL647 and Exelixis’ other compounds and the potential failure of XL647 and Exelixis’ other compounds to demonstrate safety and efficacy in clinical testing. These and other risk factors are discussed under "Risk Factors" and elsewhere in Exelixis' quarterly report on Form 10-Q for the quarter ended June 30, 2007 and other filings with the Securities and Exchange Commission. Exelixis expressly disclaims any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Exelixis’ expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.