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Committed to Patients. Making Every Moment Count. People Living with Cancer Aren’T Just Patients

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Committed to Patients. Making Every Moment Count. People Living with Cancer Aren’T Just Patients Committed to Patients. Making Every Moment Count. People living with cancer aren’t just patients. They are our family, friends, co-workers, and loved ones. Everyone at Exelixis has been touched by cancer, either through personal experience, or through our efforts at the company. We are dedicated to working on behalf of all those fighting this terrible disease. That work includes two phase 3 pivotal trials of cabozantinib in men with metastatic castration-resistant prostate cancer (mCRPC): COMET-1 and COMET-2. Prostate cancer is currently the second leading cause of cancer death among men in the United States, and patients with metastatic prostate cancer, including mCRPC, in the bone or other distant sites have a 5-year relative survival rate of only 28%.* We expect that top-line data from our COMET-1 trial this year will provide insights into the role that cabozantinib may play in improving survival for men with mCRPC. We also expect top-line data from COMET-2 before year end. If positive, results from COMET-2 could show that cabozantinib reduces both the pain associated with mCRPC as well as the usage of narcotic medication to manage that pain. In 2014, we also expect to complete the overall survival analysis from EXAM, our phase 3 pivotal trial in progressive, metastatic medullary thyroid cancer that served as the basis for cabozantinib’s first approvals in the United States and the European Union. Additional phase 3 pivotal trials are ongoing to evaluate cabozantinib in metastatic renal cell cancer and advanced hepatocellular cancer, which also have poor survival rates. Our work on these pivotal trials is just one aspect of our commitment to deliver new treatment options to the patients that need them. It’s a commitment that extends back to the earliest days of the company, and it’s what drives us to apply our knowledge, talents, and resources to oncology drug development and commercialization, day in and day out, in the hopes of making a difference for men and women living with cancer. For our family, friends, co-workers, and loved ones, and for yours and everyone’s. For patients. *http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-survival-rates Cabozantinib Disease Setting Expected Data Status Clinical Trial Metastatic Castration-Resistant Top-Line Data, Overall Survival Phase Prostate Cancer Endpoint – 2014 3 COMET-1 Metastatic Castration-Resistant Top-Line Data, Pain Palliation Phase Prostate Cancer Endpoint – 2014 3 COMET-2 Progressive, Metastatic Medullary Phase Overall Survival Readout – 2014 Thyroid Cancer 3 EXAM Metastatic Renal Cell Top-Line Data, Progression- Phase Carcinoma Free Survival Endpoint – 2015 3 METEOR Advanced Hepatocellular Top-Line Data, Overall Survival Phase Cancer Endpoint – 2016/2017 3 CELESTIAL Cobimetinib* Locally advanced/unresectable or metastatic Top-Line Data, Progression- Phase melanoma with BRAF V600 mutation Free Survival Endpoint – 2014 3 coBRIM * Cobimetinib is being developed by Roche and Genentech, a member of the Roche Group, under a collaboration agreement with Exelixis. To Our Stockholders America launched the war on cancer more than 40 years ago. Much has changed in the intervening decades, including the recognition that cancer is not a single disease. In fact, it is so highly individualized that we now talk about cancer prevention, diagnosis, and treatment in the context of personalized or precision medicine driven by the specific genetic signature of each patient’s tumor. The development of new generations of targeted cancer therapies seeks to harness this fact to Michael M. Morrissey, Ph.D. provide improved treatment options for individual patients with President and Chief Executive Officer different types of the disease. As the practice of personalized medicine evolves, however, it can feel as if the language we use to describe oncology has not: large-scale and society-wide war metaphors still persist. But the fact is, for most patients and their families cancer remains an intensely personal struggle, and is better described as a series of private, individual battles fought every day by people like you and me. Some of these battles are for survival. Some are fights to complete challenging treatment regimens. And others are a daily struggle to get to work or to celebrate life’s small pleasures. This reality challenges and motivates each of us at Exelixis to advance novel therapies that may help improve survival, manage disease symptoms, and give patients hope for the future. Seeing how COMETRIQ® (cabozantinib), our first approved product, helps patients with progressive, metastatic medullary thyroid cancer (MTC) gives us an even greater sense of urgency to provide similar experiences to more patients who are each fighting their own personal battles with cancer. We want to help patients in their individual battles by maximizing cabozantinib’s potential to treat a variety of cancers. The available clinical data demonstrate that cabozantinib can improve progression-free survival in patients with progressive, metastatic MTC. Data from other investigational trials suggest cabozantinib may also provide clinical benefit in several other types of cancer, and these findings have encouraged us to explore its use in multiple settings. Through our own studies, and our collaborations with the National Cancer Institute (NCI) and individual clinical investigators, cabozantinib’s clinical development program now includes more than 50 clinical trials in diverse indications, including five phase 3 pivotal trials. Our work in metastatic Our current priority is to evaluate cabozantinib in metastatic castration-resistant prostate cancer castration-resistant (mCRPC). Despite important treatment advances prostate cancer reflects over the past several years, the American Cancer Society estimates that nearly 30,000 men will die of our commitment to prostate cancer in the United States this year, and develop new treatment many more will struggle to live with it.* Our focus on mCRPC is based on phase 2 clinical data suggesting options for the patients cabozantinib can provide diverse clinical benefits, including the ability to target both soft tissue lesions that need them most. and bone metastases, and their associated pain. No approved therapy has been shown to address all three of these important aspects of the disease. So if cabozantinib is successful in phase 3 pivotal trials and approved, it could become a unique treatment option. We’re conducting two phase 3 pivotal trials in mCRPC, and we expect top-line data from both in 2014. The trials are in a late-stage setting, in men who have previously been treated with chemotherapy and at least one of two newer androgen pathway- targeting therapies. This patient population has not been extensively studied, and our work here reflects our commitment to develop new treatment options for the patients that need them most. Our COMET-1 trial is evaluating overall survival in patients treated with cabozantinib compared with prednisone. The trial is fully enrolled and, in March 2014, the Independent Data Monitoring Committee completed a pre-planned interim analysis and recommended COMET-1 proceed to its final analysis. Our COMET-2 trial is evaluating pain palliation in patients with bone metastases treated with cabozantinib compared with mitoxantrone and prednisone; this study continues to enroll. As we await the availability of top-line data from both trials, we are preparing to quickly file with U.S. and European regulatory agencies should the data be positive. In 2013, we also initiated additional phase 1b/2 trials in patients with mCRPC to evaluate cabozantinib in combination with other agents in earlier lines of therapy. All of our work in prostate cancer is directed at broadening the potential clinical utility of cabozantinib and expanding the number of patients who may benefit from it. We are keenly aware that patients with other cancers also face limited or suboptimal treatment options. To potentially meet these needs and support thousands of additional patients, we initiated pivotal trials of cabozantinib in metastatic renal *http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-key-statistics cell cancer and advanced hepatocellular cancer in 2013, and are planning to initiate a phase 2 clinical trial in a specific subset of non-small cell lung cancer patients who have RET gene fusions. An additional fourteen phase 1 and 2 clinical trials are being conducted under our collaboration with the NCI; data from these trials will help guide our selection of additional indications for pivotal studies. Our investigator-sponsored trial (IST) program further expands cabozantinib’s clinical development program and enables clinicians to design trials that reflect patients’ unmet needs in real world settings. Cabozantinib is not the only Exelixis-discovered compound with the potential to support patients in their battle with cancer. Roche and Genentech, Inc., a member of the Roche Group, are developing cobimetinib for the treatment of locally advanced/unresectable or metastatic melanoma carrying a BRAF V600 mutation. Cobimetinib is We know our success a highly selective inhibitor of MEK that Exelixis will be defined by the discovered, investigated in phase 1 clinical studies, and partnered with Genentech in 2006. Encouraging data benefit we may bring from a phase 1 trial of cobimetinib in combination to patients. with vemurafenib were presented in 2013. Although the trial was primarily designed to evaluate safety of the combination regimen, objective responses were observed in 85% of patients who received the combination and had not previously been treated with a BRAF inhibitor. Roche and Genentech are currently conducting a phase 3 pivotal trial evaluating vemurafenib alone or in combination with cobimetinib in previously untreated patients with malignant melanoma harboring the BRAF V600 mutation, and top-line data from this trial are expected this year. If cobimetinib successfully reaches the market, our agreement with Genentech includes a U.S. profit share and co-promotion agreement, and Exelixis is also eligible for royalties on sales outside the United States.
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