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Exelixis, Inc.

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PLEASE SCROLL DOWN TO THE RESULTS SECTION (below) TO SEE THE OUTCOME OF THIS EVENT.

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Gisela M. Schwab, MD, EVP and CMO, gave guidance for dataq from the CABOSUN trial. She stated, "The CABOSUN trial is a randomized phase-II study comparing Cabozantinib versus Sunitinib in first-line therapy of intermediate or poor risk patients per the standard risk classification. The primary endpoint is PFS and the study achieved its target enrollment of 150 patients in March of 2015, given the historical PFS duration in patients with intermediate or poor risk RCC in the first-line setting, we are expecting data in the first half of 2016."
Source: Q4 2015 earnings conference call, 2/29/16.

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he Alliance for Clinical Trials in Oncology (The Alliance) recently notified Exelixis that CABOSUN, the randomized phase 2 study of cabozantinib versus sunitinib in the first-line RCC setting, met its enrollment target of 150 patients determined to be intermediate or poor risk by the Heng criteria. The primary endpoint of CABOSUN is PFS. Given the historical PFS duration for sunitinib in similar patients in the first-line setting, Exelixis anticipates data from the trial in 2016. CABOSUN is being conducted by The Alliance as part of Exelixis’ collaboration with the NCI-CTEP.
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Source: press release, 4/30/15. http://www.exelixis.com/investors-media/press-releases?cpurl=http%3A%2F%...

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Randomized Phase II Study Comparing Cabozantinib (NSC #761968) With Commercially Supplied Sunitinib in Patients With Previously Untreated Locally Advanced or Metastatic Renal Cell Carcinoma
Estimated Enrollment: 150
Study Start Date: July 2013
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
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Source: clinical trials.gov. https://clinicaltrials.gov/ct2/show/NCT01835158?term=cabozantinib&phase=...

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
Cabozantinib - Renal cell carcinomaUrologyRenal cell carcinomaTyrosine kinase inhibitorc-Met and VEGFR-2

Mechanism of action: Cabozantinib is an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several tyrosine receptor kinases. Specifically, cabozantinib appears to have a strong affinity for the hepatocyte growth factor receptor (Met) and vascular endothelial growth factor receptor 2 (VEGFR2), which may result in inhibition of tumor growth and angiogenesis, and tumor regression. This agent has also been shown to inhibit mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (Flt3) and tyrosine-protein kinase receptor (Tie-2).

Phase of Development: II

Event Type: Data: Phase II trial results

Dates: 2016-03-01 - 2016-06-30

Results:

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Exelixis Announces Positive Results from Phase 2 CABOSUN Trial of Cabozantinib Versus Sunitinib in Previously Untreated Advanced Renal Cell Carcinoma Presented at ESMO 2016
– Cabozantinib met the primary endpoint of improving progression-free survival as compared to sunitinib, decreasing the rate of disease progression or death by 31 percent –

– Objective response rate significantly improved: 46 percent for cabozantinib versus 18 percent for sunitinib –

– Exelixis to host investor and media webcast from Copenhagen to discuss the data on Monday, October 10 –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--Oct. 10, 2016-- Exelixis, Inc. (NASDAQ:EXEL) today announced detailed results from the CABOSUN randomized phase 2 trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma (RCC) with intermediate- or poor-risk disease per the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Principal investigator Toni K. Choueiri, M.D. will present detailed data from late-breaking CABOSUN abstract [#LBA30_PR] today in the Presidential Symposium 3 session, starting at 16:30 CEST (local Copenhagen time) / 10:30 a.m. EDT / 7:30 a.m. PDT at the European Society for Medical Oncology (ESMO) 2016, which is being held October 7 – 11, 2016 in Copenhagen.

CABOSUN was conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP).

In CABOSUN, with a median follow-up of 20.8 months, cabozantinib demonstrated a clinically meaningful and statistically significant 31 percent reduction in the rate of disease progression or death [HR 0.69, 95% CI (0.48-0.99), one-sided P=0.012]. The median progression-free survival (PFS) for cabozantinib was 8.2 months versus 5.6 months for sunitinib, corresponding to a 2.6 months (46 percent) improvement favoring cabozantinib over sunitinib. PFS benefits were independent of IMDC risk group (intermediate or poor risk) and presence or absence of bone metastases at baseline. The results for sunitinib were in line with a previously published retrospective analysis of 1,174 intermediate- and poor-risk RCC patients from the IMDC database, which documented a median PFS of 5.6 months with a first-line targeted therapy, mainly sunitinib, in this patient population.1

Objective response rate (ORR) was also significantly improved, at 46 percent (95% CI 34% – 57%) for cabozantinib versus 18 percent (95% CI 10% to 28%) for sunitinib. With a median follow up of 22.8 months, median overall survival was 30.3 months for cabozantinib versus 21.8 months for sunitinib [HR 0.80, 95% CI (0.50 - 1.26)].

“The results presented today support the potential of cabozantinib to become a new therapeutic option for previously untreated patients following their diagnosis with advanced kidney cancer,” said Toni K. Choueiri, M.D., Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and chair of the CABOSUN study. “Not only has cabozantinib surpassed sunitinib, the current standard of care, in progression-free survival and objective response rate, cabozantinib’s effects on progression-free survival were also consistently favorable across patient stratification subgroups including IMDC intermediate versus poor-risk groups and presence or absence of bone metastases.”

“We at the Alliance for Clinical Trials in Oncology are pleased that CABOSUN has successfully demonstrated that cabozantinib has the potential to benefit patients with advanced renal cell carcinoma as a first-line therapy,” said Michael J. Morris, M.D., Associate Member at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary Committee. “We are grateful to everyone who has participated in the trial, especially the physicians, patients and their families.”

Based on these results, Exelixis plans to submit a Supplemental New Drug Application (sNDA) for cabozantinib as a treatment of first-line advanced renal cell carcinoma, and is working with the Alliance to transfer the complete CABOSUN clinical database to Exelixis.

“The past year has seen a tremendous level of progress in the treatment of kidney cancer, and we are excited to be at the forefront of bringing these advancements to patients,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “Patients in the first-line setting with either intermediate- or poor-risk disease progress rapidly with sunitinib, a current standard of care; therefore, there is a clear need for new options that provide improved clinical benefit in this difficult to treat patient population. To that end, based on the CABOSUN results, we are planning to submit a supplemental New Drug Application in the United States for cabozantinib as a first-line treatment for advanced renal cell carcinoma.”

CABOSUN enrolled 157 patients with previously untreated advanced RCC: 80.9 percent of patients were intermediate risk per IMDC criteria and 19.1 percent were poor risk, 36.3 percent of patients had bone metastases, 46 percent of patients had ECOG Performance Status (PS) 0, 41 percent had ECOG PS 1, and 13 percent had ECOG PS 2. All patients were included in the efficacy analyses that followed the intent-to-treat principle. Tumor assessments were performed by the investigators following RECIST criteria. At the time of the analysis of the primary endpoint of PFS, the median duration of treatment in CABOSUN was 6.9 months with cabozantinib and 2.8 months with sunitinib; 13 patients continued on cabozantinib treatment versus 2 patients on sunitinib treatment. Dose reductions occurred for 58 percent and 49 percent of patients, respectively. Discontinuation rate due to an adverse event was 20 percent with cabozantinib and 21 percent with sunitinib.

One hundred and fifty patients were evaluable for safety. Ninety-nine percent of patients on both arms experienced at least one adverse event. The most common all causality grade 3 or 4 adverse events observed in more than 5 percent of patients were hypertension (28 percent), diarrhea (10 percent), palmar-plantar erythrodysesthesia (8 percent), and fatigue (6 percent) in the cabozantinib arm, and hypertension (22 percent), fatigue (15 percent), diarrhea and thrombocytopenia (both 11 percent), and oral mucositis (6 percent) in the sunitinib arm. Treatment-related grade 5 events occurred in three patients in the cabozantinib arm (acute kidney injury, sepsis and jejunal perforation) and two patients in the sunitinib arm (sepsis and vascular disorder).
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Source: press release, 10/10/16. http://www.exelixis.com/investors-media/press-releases

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Exelixis Provides Update on Timing of Key Cabozantinib Clinical Data Presentation at the ESMO 2016 Congress
- CABOSUN results now subject of an oral presentation in Presidential Symposium 3 on Monday, October 10 -

SOUTH SAN FRANCISCO--(BUSINESS WIRE)--Sep. 20, 2016-- Exelixis, Inc. (NASDAQ:EXEL) today provided an update on the timing of a key data presentation for cabozantinib at the European Society for Medical Oncology (ESMO) 2016 Congress, which is being held October 7-11, 2016 in Copenhagen, Denmark. Detailed results from CABOSUN, the randomized phase 2 clinical trial of cabozantinib compared with sunitinib in patients with previously untreated advanced renal cell carcinoma (RCC), has been selected for the Presidential Symposium 3 session on Monday, October 10, 2016, starting at 16:30 CEST (local Copenhagen time) / 10:30 a.m. EDT / 7:30 a.m. PDT.

The full logistical details for the CABOSUN data presentation are as follows:

Oral Presentation

[LBA30_PR] “CABOzantinib versus SUNitinib (CABOSUN) as initial targeted therapy for patients with metastatic renal cell carcinoma (mRCC) of poor and intermediate risk groups: Results from ALLIANCE A031203 Trial.”

Dr. Toni Choueiri, Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA

Session: Presidential Symposium 3, Monday, October 10, 2016 – 16:30-18:10 CEST, Copenhagen room

Note: This is a National Cancer Institute Cancer Therapy Evaluation Program (NCI-CTEP) study.

The late-breaking CABOSUN abstract was initially slated for an oral presentation at a Proffered Paper session on Saturday, October 8, 2016. Exelixis previously announced that data from the Exelixis-discovered compounds cabozantinib and cobimetinib would be the subject of fifteen presentations at the ESMO 2016 Congress. For full details on Exelixis’ presence at the conference, please see the company’s press release issued on August 31, 2016.
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Source: press release, 9/20/16. http://www.exelixis.com/investors-media/press-releases

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Exelixis Announces Results from Randomized Phase 2 Trial CABOSUN Demonstrate Cabozantinib Significantly Improved Progression-Free Survival versus Sunitinib in Previously Untreated Advanced Renal Cell Carcinoma
– Exelixis to consult with regulatory authorities to determine next steps in development and submission strategy for cabozantinib in first-line renal cell carcinoma –

SAN FRANCISCO--(BUSINESS WIRE)--May 23, 2016-- Exelixis, Inc. (NASDAQ:EXEL) today announced positive top-line results from the CABOSUN randomized phase 2 trial of cabozantinib in patients with previously untreated advanced renal cell carcinoma (RCC). The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for cabozantinib compared with sunitinib in patients with advanced intermediate- or poor-risk RCC. The safety data in the cabozantinib-treated arm of the study were consistent with those observed in previous studies in patients with advanced RCC. CABOSUN is being conducted by The Alliance for Clinical Trials in Oncology as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP). The final results from CABOSUN will be submitted for presentation at a future medical conference.

“The positive outcome of CABOSUN is extremely exciting, as it marks the very first time that a therapy has shown a progression-free survival benefit over standard of care first-line treatment sunitinib for patients with previously untreated advanced renal cell carcinoma,” said Toni K. Choueiri, M.D., Clinical Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute and chair of the CABOSUN study. “Based on these findings, cabozantinib may have the potential to become a new gold standard for previously untreated patients following their diagnosis with advanced kidney cancer.”

“All of us at the Alliance for Clinical Trials in Oncology are very gratified to have successfully demonstrated the potential of first-line cabozantinib to benefit patients with renal cell carcinoma in the CABOSUN study. This trial exemplifies how NCI-sponsored studies can be efficient, accrue rapidly, and yield results highly relevant to the field,” said Michael J. Morris, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center, and Chair of the Alliance Genitourinary (GU) Committee.

Exelixis will share the results of CABOSUN with regulatory authorities to discuss potential next steps in the development and submission strategy for cabozantinib as a treatment of first-line advanced renal cell carcinoma. Exelixis is also working closely with clinical advisors on the development plan for cabozantinib in future clinical trials in other genitourinary malignancies.

“Demonstrating an improvement in progression-free survival with cabozantinib compared to sunitinib as a first-line treatment represents an important milestone for patients with previously untreated RCC,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We are thrilled to be a part of the many recent advances in the treatment of advanced kidney cancer and would like to thank the patients, physicians, nurses, caregivers, the Alliance cooperative group and NCI-CTEP who made this clinical trial possible. We look forward to pursuing next steps in the development of cabozantinib in the first-line treatment of patients with advanced RCC and other GU malignancies.”
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Source: press release, 5/23/16. http://www.exelixis.com/investors-media/press-releases

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