Commentary from January 18
Back in December, the FDA placed a partial hold on Exelixis’ (EXEL) Phase II XL999 cancer program due to cardiovascular events and its share price took a dip and has bounced back. Exelixis is optimistic that Phase II studies can resume in the first half of 2007 using lower doses and slower infusion rates in lung cancer and acute myelogenous leukemia patients who have shown benefit from XL999. More importantly, XL999 has shown early Phase II clinical activity.
In addition, Exelixis will likely present proof of concept data to GlaxoSmithKline (GSK) by mid-2007 on small molecule cancer drug candidates XL647, XL999, XL784, and XL880. The company expects that GSK will choose one or two of these for further development, with the remaining two to three returning to Exelixis. Upon making a selection, GSK will make a milestone payment to Exelixis of approximately $75 to $85 million and assume all further clinical responsibilities.
The Phase II programs for XL880 in papillary or hereditary renal cell carcinoma and XL647 in a subset of first-line non-small cell lung cancer (NSCLC) patients will each generate data in the first half of 2007. Exelixis plans to initiate further Phase II trials with XL880 in head and neck cancers, and with XL647 in first-line NSCLC, Tarceva-refractory NSCLC, and breast cancer in the first half of 2007.
Multiple other programs are advancing into clinical development. Among these, the Phase II program for XL784 in diabetic nephropathy is expected to be fully enrolled by mid-2007 with possible data available in the third quarter of 2007. Phase II trials will also be initiated for pipeline drugs XL184 (solid and hematologic cancers) and XL820 (potentially in gastrointestinal stromal tumor, ovarian, and melanoma cancers) in the first half of 2007. Nadine Wong and her team believe the remaining Phase I and preclinical pipeline will also move forward in 2007, and up to eight Phase I trials could be ongoing by mid-2007.
With seven compounds in clinical development and another six likely to enter over the next 12 months, Exelixis shares will outperform as multiple candidates progress through clinical testing.
Recently, Exelixis has entered into a couple of partnerships. Exelixis agreed to collaborate with Bristol-Myers Squibb on discovery, development and commercialization of cancer treatments. Under the collaboration, Exelixis will use its drug discovery platform and will identify and be responsible for preclinical development of small molecule drug candidates. Bristol- Myers Squibb will have the right to select up to three investigational new drug candidates against three different targets and will lead all global activities. The two parties will co-develop and co-commercialize the programs in the U.S., Bristol-Myers Squibb will pay Exelixis $60 million in cash upfront, and Exelixis will also receive $20 million for each of up to three different drug candidates selected by Bristol-Myers Squibb.
The other agreement is with Genentech for the worldwide co-development of XL518, a small-molecule inhibitor of MEK. Exelixis submitted an Investigational New Drug application for XL518 to the FDA on MEK, also known as mitogen activated protein kinase (MAPK), a key component of the AS/RAF/MEK/ERK pathway, which is frequently activated in human tumors. Inappropriate activation of the MEK/ERK pathway can promote tumor growth and survival.
Exelixis’ pipeline has great potential.