Pipeline

About Exelixis

At Exelixis, our commitment to improving the treatment of cancer has driven us to pursue an uncommon path and a different approach to developing drugs. We have built critical mass throughout all areas of our research and development infrastructure, making it possible to achieve unparalleled productivity while retaining an unwavering commitment to quality. Our biology-based and data-driven approach is designed to enable the development of first-in-class or best-in-class compounds that will significantly improve the care and outcomes of cancer patients. Our unique strategy is designed to ensure a steady stream of high quality compounds that address the changing needs of clinical oncology.

Recognizing that many of today's cancer patients have significant unmet medical needs, our actions are imbued with a sense of urgency that mandates that we think large and move fast, pursuing a better way to better medicine.

Spectrum Selective Kinase Inhibitors

Our first generation clinical development candidates are each designed to simultaneously target multiple members of a family of proteins known as receptor tyrosine kinases (RTKs). These proteins are involved in key cancer-related processes, including cell growth and proliferation, survival, metastasis, tumor angiogenesis and drug resistance. RTK inhibition has been validated as a therapeutic approach to treating cancer by the approval of several drugs that target selected RTKs.

Although the currently approved targeted therapies have helped to advance the treatment and outcomes of cancer patients, in many cases these drugs are not sufficient, either as monotherapy or in drug combinations, to provide durable responses. Multiple pathways and processes contribute to tumor development, progression and metastasis. Thus, blocking a single pathway may not in itself be sufficient to stabilize or cure disease.

At Exelixis, we are developing compounds that are designed to simultaneously target multiple RTKs. These compounds have been exhaustively optimized for tolerability, potency, specificity, half-life and dosing schedule against each of their multiple targets, which may provide improved efficacy and enhanced safety profiles compared with combinations of single-target drugs that have not been optimized for use together. This approach may provide a way to inhibit numerous cancer processes - such as angiogenesis, cell growth or drug resistance - in a highly concerted manner with a single drug. In turn, this may achieve a clinically meaningful balance between the broad effects of chemotherapy and the favorable safety and tolerability profiles of targeted agents.

Inhibiting Downstream Signaling Pathways

Recent breakthroughs in molecular oncology have identified a number of critical downstream signaling cascades that are activated by RTKs implicated in the development of cancer. Our second-generation compounds are focused on inhibiting these critical downstream pathways, which include the PTEN/PI3K, RAS/RAF/MEK/ERK and JAK/STAT cascades. Direct mutational activation of these pathways, either through loss of tumor suppressors (PTEN), or acquisition of activating mutations (RAS, RAF, PI3K, JAK2) is a frequent occurrence in human tumors, and confers resistance to RTK inhibitors.

At Exelixis, we are leveraging our expertise in comparative genomics and molecular biology to explore the complex interactions among key signaling pathways in cancer cells. We believe that a comprehensive understanding of the roles that these pathways play in cancer will enhance our ability to develop novel drugs that may advance cancer treatment and help overcome resistance to current therapies. Already we have made significant progress in developing a portfolio of compounds that inhibit critical components of downstream signaling pathways with high specificity and activity.

Compounds inhibiting the RAS and PI3K pathways are in clinical development and additional compounds targeting PI3K and JAK/STAT are expected to advance to clinical development later in 2007.