Forward-Looking Statements

Transcription

1 July 20, 2015 METEOR: Phase 3 Pivotal Trial of Cabozantinib Meets Primary Endpoint of Improving Progression-Free Survival (PFS) in Patients with Metastatic Renal Cell Carcinoma (mrcc) Exelixis, Inc. (NASDAQ: EXEL)

2 Forward-Looking Statements This presentation contains forward-looking statements, including, without limitation, statements related to: the continuation of the METEOR trial to the final OS analysis anticipated in 2016; Exelixis plan to complete regulatory filings for cabozantinib for the treatment of RCC in the U.S. and EU in early 2016; Exelixis targeting of a data presentation for the METEOR trial later this year; the clinical, therapeutic and commercial potential of, and opportunities for, cabozantinib as a treatment for RCC; the continued development of cabozantinib in additional RCC settings, as well as in combination with immunotherapies; expected data results from the CABOSUN trial in 2016; Exelixis plan to continue to invest in expanding the cabozantinib RCC opportunity to additional patient populations and combinations; the continued development program for cabozantinib, including ongoing pivotal trials in RCC and HCC, trials conducted with Exelixis collaborators at NCI-CTEP and investigator sponsored trials; Exelixis plans to move forward with urgency and execution around the goal of delivering on the potential of cabozantinib for patients with mrcc, on business development activities related to seeking a partner for the ex-u.s. commercialization of cabozantinib and obtaining proceeds to support the build-out of a commercial infrastructure for a potential RCC launch and the extensive development path for cabozantinib; anticipated regulatory decisions for cobimetinib from the United States and European Union before the end of 2015; the economic terms of Exelixis collaboration with Genentech if cobimetinib successfully reaches the market, including the plan to share U.S. profits and losses and Exelixis eligibility to receive royalties on sales of cobimetinib outside of the U.S.; Exelixis belief that the addition of Chris Senner as EVP and CFO will serve the company well in its continued focus on transforming into a fully-integrated commercial organization; and Exelixis priorities for the rest of 2015, including, expediting the U.S. and EU regulatory filings of cabozantinib in metastatic RCC, obtaining potential U.S. and EU approval of cobimetinib for advanced BRAF V600 mutationpositive melanoma, entering into an ex-u.s. partnership to maximize the clinical and commercial opportunity of cabozantinib on a global basis and expediting the enrollment of CELESTIAL, the company s pivotal phase 3 study in HCC. Words such as continue, anticipated, planning, targeting, potential, may, opportunity, priority, expected, moving forward, goal, entitled, will, focus, or other similar expressions, identify forward-looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. These forward-looking statements are based upon Exelixis current plans, assumptions, beliefs, expectations, estimates and projections. Forwardlooking statements involve risks and uncertainties. Exelixis actual results and the timing of events could differ materially from those anticipated in the forward-looking statements as a result of these risks and uncertainties, which include, without limitation: the availability of data at the expected times; risks related to the potential failure of cabozantinib or cobimetinib to demonstrate safety and efficacy in clinical testing; the clinical, therapeutic and commercial value of cabozantinib and cobimetinib; uncertainties of the regulatory review and approval processes and Exelixis ability to comply with applicable legal and regulatory requirements; Exelixis dependence on its relationship with Genentech/Roche with respect to cobimetinib and Exelixis ability to maintain its rights under the collaboration; the sufficiency of Exelixis capital and other resources; the uncertain timing and level of expenses associated with the development of cabozantinib; Exelixis ability and the ability of its collaborators to conduct clinical trials of cabozantinib and cobimetinib sufficient to achieve a positive completion; Exelixis ability to enter into new collaborations; market competition; changes in economic and business conditions and other factors discussed under the caption Risk Factors in Exelixis quarterly report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on April 30, 2015, and in Exelixis other filings with the SEC. The forward-looking statements made in this presentation, including any oral presentation accompanying it, speak only as of the date on which the statements are made. Exelixis expressly disclaims any duty, 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. 2

3 Today s Agenda Introduction Susan Hubbard, Investor Relations Opening Remarks Mike Morrissey, Ph.D., President and CEO METEOR Data Highlights Gisela Schwab, M.D., EVP and CMO Closing Mike Morrissey, Ph.D., President and CEO Joining for Q&A Peter Lamb, Ph.D., EVP, Discovery Research and CSO Chris Senner, EVP and CFO Debbie Burke, SVP, Finance and Controller PJ Haley, VP, Commercial Press release and webcast (live and archived) available at 3

4 Opening Remarks Michael M. Morrissey, Ph.D., President and CEO

5 Positive Results for METEOR Statistically significant improvement in progression-free survival (PFS) for cabozantinib as compared to everolimus in mrcc Strong positive trend for overall survival (OS) favoring cabozantinib at interim analysis; study to continue to final OS analysis, anticipated 2016 Cabozantinib was generally well tolerated in this 2L RCC population, which resulted in a low discontinuation rate Planning regulatory filings in U.S. and EU by early 2016; targeting data presentation later this year 5

6 Charting the Path to METEOR s Outcome cabozantinib VEGFR MET VEGF AXL RCC VHL Excellent match between target inhibition profile of cabozantinib and fundamental characteristics of RCC tumor biology Phase 1b results suggested potential for cabozantinib to demonstrate benefit over leading 2L therapies Pre-phase 3 meetings with U.S. / EU regulatory authorities and experts worldwide led to robust trial design Source for Phase 1b data: Choueiri TK, et al. Ann Oncol

7 METEOR Results in Perspective ü Meaningful improvement in PFS vs. leading 2nd line agent ü Potential for showing an improvement in OS a unique and differentiating feature ü Novel mechanism of action may translate to improved clinical benefit in RCC 7

8 Large and Growing Global Patient Population Kidney Cancer 295,000 cases 1 Worldwide 134,000 deaths 1 61,500 new cases each year 2 United States 14,000 deaths annually 2 Clear-cell RCC represents 70-75% of all renal cancers 3 RCC Second-Line or Later Setting, Drug-Eligible Patients Worldwide 37,000 patients 4 United States 17,000 patients 4 1. Fitzmaurice et al., JAMA Oncol Jul 1;1(4): Jonasch et al. BMJ (2014) vol. 349, g4797. Iliopolous O, J Clin Oncol Dec 10;24(35): Sources: ACS Cancer Facts and Figures 2015; Heng et al., Ann Oncol (2012) vol. 23 no. 6; internal data on file; Motzer et al., N Engl J Med (2007) vol. 356 no. 2; NCIN (UK) report, April 2014, Available at 8

9 Unmet Need, Commercial Opportunity in Second-Line RCC Relatively mature treatments, with similar and modest PFS benefits Total global sales of $1B for agents in this setting (2014) 1 Opportunities for differentiated agents Everolimus Axitinib FY 14 Global Sales for RCC $408M 2 $410M 2 PFS in sunitinib-pretreated 2 nd -line population 4.6 months months 4 1. Publicly available information. 2. Everolimus calculation is an annualized run-rate based on Novartis Q3 14 disclosure of $408M in revenue, of which 25% was RCC. 3. Calvo, et al., Eur J Cancer (2012) vol. 48 no Rini, et al., Lancet (2011) vol. 378 no

10 METEOR Data Highlights Gisela Schwab, M.D., EVP and CMO

11 METEOR Phase 3 Pivotal Trial Design METEOR o 658 patients with clear cell RCC who have received and progressed on at least one VEGFR TKI o Randomized, open-label trial; no crossover permitted o ~200 sites predominantly in W. Europe, North America, Australia ARM A N = 658 1:1 randomization ARM B Cabozantinib 60 mg daily Everolimus 10 mg daily Enrollment completed in November 2014 Endpoints: Primary: Progression-Free Survival, conducted once 259 events from the first 375 patients enrolled occurred Statistical modeling assumptions for primary endpoint: 5.0 months for everolimus, 7.5 months for cabozantinib Designed to provide 90% power to detect a hazard ratio (HR) of with a two-sided alpha of 0.05 Secondary: Overall Survival and Objective Response Rate Study initiated in May 2013, FPI August

12 METEOR: An International, Collaborative Effort Over 200 Sites Worldwide, with Majority of Patients Enrolled at Sites in North America, EU and Australia 12

13 METEOR Efficacy Results: Highly Statistically Significant Increase in Progression-Free Survival Hazard Ratio % CI p< Highly statistically significant and clinically meaningful PFS benefit for cabozantinib vs. everolimus in first 375 patients enrolled 42% reduction in risk of disease progression or death Overall Survival (OS; Secondary Endpoint) 0.67 Unadjusted 95% CI p=0.005 Strong trend favoring cabozantinib seen in interim OS analysis triggered by the primary analysis for PFS YY.Y MONT HS OS data immature at the time of data cut off; pre-specified X% decrease in risk p-value of death of (HR=0.xx) to achieve statistical significance was not reached Highly statistically significant p < 0.xxxxx Final OS analysis anticipated in

14 METEOR Safety Observations Rates of serious AEs were generally lower in this younger RCC patient population compared to populations studied previously Serious adverse events (SAEs) were similar between treatment arms The rate of treatment discontinuation due to AEs was low (10%), and consistent with that previously reported for everolimus. May be due in part to: The optimized dose of cabozantinib at 60 mg per day High level of familiarity of RCC investigators with the use of both everolimus and the VEGFR targeting TKIs 14

15 Regulatory Update In U.S., granted Fast Track Designation in April 2015 U.S. and EU regulatory filings planned for early 2016 Completing these filings is our highest priority 15

16 Other Ongoing Clinical Development in RCC CABOSUN Phase 2 Trial in First-Line RCC Setting Cabozantinib vs. sunitinib in 150 advanced RCC patients classified as intermediate or poor risk by the standard criteria Completed enrollment March 2015, data expected in 2016 Conducted by The Alliance cooperative group under NCI-CTEP IND Phase 1 Immunotherapy Combination Trial Cabozantinib with nivolumab, or with nivolumab and ipilimumab, in patients with advanced/metastatic urothelial (bladder), RCC and other genitourinary tumors Initiated July 2015 Conducted by NCI-CTEP Continuing to invest in expanding the cabozantinib RCC opportunity to additional patient populations and combinations 16

17 Broad Clinical Development Program for Cabozantinib In total, more than 45 planned or ongoing studies EXELIXIS ONGOING PIVOTAL TRIALS METEOR (mrcc) CELESTIAL (HCC) NCI / CTEP TRIALS Exploring cabozantinib s potential in a wide variety of cancers 20 studies/year for period of five years ~15 trials ongoing INVESTIGATOR SPONSORED TRIALS Broad variety of tumor types under investigation Leading institutions and researchers worldwide 17

18 DRAFT * FOR INTERNAL REVIEW ONLY Closing Michael M. Morrissey, Ph.D., President & CEO

19 Moving Forward with Urgency and Execution With data in hand, an even greater sense of urgency around the goal of delivering on the potential of cabozantinib for patients with mrcc Ongoing business development activities seeking a partner for commercialization ex-u.s.; proceeds to support build-out of commercial infrastructure for a potential RCC launch METEOR results represent a major milestone for Exelixis, and an important step along an extensive development path for cabozantinib 19

20 Ongoing Commercial Planning for Cobimetinib for Advanced BRAF V600 Mutation-Positive Melanoma Cobimetinib: a selective inhibitor of MEK, a component of the RAS/RAF/ MEK/ERK pathway activated in wide variety of tumors An Exelixis-discovered compound In development with Genentech, a member of the Roche Group Genentech / Roche U.S. and EU marketing applications under review for cobimetinib used in combination with vemurafenib in patients with advanced melanoma harboring a BRAF V600 mutation Filings based on data from cobrim phase 3 pivotal trial U.S. NDA received Priority Review, PDUFA date of November 11, 2015 Combined sales forces trained and prepared to execute on the potential launch EU MAA filed in September 2014, Roche has guided anticipated action by YE 15 Economic terms of collaboration Co-promote, profit share in U.S.; initial 50/50 share of U.S. profits/losses Entitled to a low double digit royalty on ex-u.s. revenue 20

21 Welcome to Chris Senner Joined Exelixis as EVP and CFO (July 15, 2015) Nearly 25 years of experience in biopharmaceutical finance Deep experience in global financial operations and controls, strategic planning and analysis, supply chain finance and business development Previously at Gilead Sciences as Vice President, Corporate Finance (5 years) and Wyeth (18 years) in a variety of financial roles with increasing responsibility His expertise will serve the company well in its continued focus on transforming into a fully-integrated commercial organization 21

22 Exelixis Priorities for the Rest of the Year 1 Prioritize our efforts to expedite the U.S. and EU regulatory filings of cabozantinib in metastatic RCC 2 Obtain the potential U.S. and EU approval of cobimetinib for advanced BRAF V600 mutation-positive melanoma 3 Enter into an ex-u.s. partnership to maximize clinical and commercial opportunity of cabozantinib on a global basis 4 Expedite the enrollment in CELESTIAL, our pivotal phase 3 study in hepatocellular carcinoma 22

23 Thank You to the more than 650 patients who are taking part in the METEOR trial...to the physicians, nurses, staff and families who care for them. to our vast network of collaborators. and to the entire Exelixis team, who work tirelessly and with passion to discover, develop and bring new treatments to people in their fight against cancer. 23

24 Question & Answer Session

25 July 20, 2015 METEOR: Phase 3 Pivotal Trial of Cabozantinib Meets Primary Endpoint of Improving Progression-Free Survival (PFS) in Patients with Metastatic Renal Cell Carcinoma (mrcc) Exelixis, Inc. (NASDAQ: EXEL)