On January 12, 2020 Exelixis, Inc. (Nasdaq: EXEL) reported its key priorities and anticipated milestones for 2020-21, including generating top-line data from key clinical trials, completing enrollment of ongoing studies, initiating new pivotal trials, and progressing its mid-stage and early pipeline (Press release, Exelixis, JAN 12, 2020, View Source [SID1234553029]). The company intends to make appropriate investments to maximize the clinical development opportunities for CABOMETYX (cabozantinib), which Exelixis believes could lead to as many as four additional approved indications by year-end 2021, while concurrently working to advance a pipeline of potential new Exelixis medicines through internal drug discovery and business development.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Exelixis is moving decisively to pursue important new indications for our lead product, CABOMETYX, and potentially bring new medicines to cancer patients in need of better treatment options," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer of Exelixis. "Cabozantinib is now an oncology franchise with global net revenue of more than $1 billion on an annual basis. Over the course of the next two years, we intend to expand the depth and breadth of the cabozantinib development program by obtaining top-line results from as many as six ongoing trials with label-enabling potential and initiating at least three new pivotal trials. If the data from these trials are market differentiating and result in regulatory approvals, we believe we could dramatically expand the number of patients that might benefit from cabozantinib, addressing a potential patient population more than four times greater in magnitude than our current opportunities in advanced renal cell and previously treated hepatocellular cancer. This result could have a significant impact on our business as we continue to invest in a multi-product oncology portfolio with the potential to lead to annual U.S. net product revenues approaching $4 billion by 2025."

Dr. Morrissey continued: "We continue to make strong progress in building our pipeline. Between our internal discovery activities and the four business development deals we’ve signed over the past two years, there are approximately 20 ongoing discovery programs focused on potentially adding novel and differentiated assets to the Exelixis development portfolio. In 2020, we believe these efforts could yield as many as three Investigational New Drug filings, and we also expect to advance multiple additional programs into preclinical development. As cabozantinib advances, we believe this earlier stage work, which we intend to complement with external strategic assets by leveraging our strong balance sheet, could bring forth a new generation of Exelixis medicines with the potential to strengthen our business and help cancer patients recover stronger and live longer."

Anticipated Cabozantinib Data Readouts in 2020

CheckMate 9ER: Bristol-Myers Squibb (BMS) and Exelixis anticipate results from CheckMate 9ER, the phase 3 pivotal trial evaluating cabozantinib in combination with nivolumab in previously untreated advanced or metastatic renal cell carcinoma (RCC), in the first half of 2020. BMS is sponsoring this trial, which completed enrollment in early 2019. If the data are positive, Exelixis, BMS and their respective partners plan to expeditiously pursue regulatory filings.
COSMIC-311: In the first half of 2020, Exelixis anticipates completing enrollment of the first 100 patients in this phase 3 pivotal trial evaluating cabozantinib versus placebo in patients with radioactive iodine-refractory differentiated thyroid cancer who have progressed after up to two VEGF receptor-targeted therapies. As planned, Exelixis expects to conduct an interim analysis in these first 100 patients for the co-primary endpoints of objective response rate and progression-free survival (PFS) and reach total enrollment of 300 patients in the second half of 2020.
COSMIC-312: Exelixis expects to complete enrollment in the first half of 2020 and conduct the analysis for the co-primary endpoint of PFS and an interim analysis for overall survival (OS) for this phase 3 pivotal trial evaluating cabozantinib in combination with atezolizumab (TECENTRIQ), Genentech’s anti-PD-L1 immune checkpoint inhibitor (ICI), versus sorafenib in previously untreated advanced hepatocellular carcinoma (HCC). The analyses are event-driven and may occur as early as in the second half of 2020.
COSMIC-021: COSMIC-021, the phase 1b trial evaluating cabozantinib in combination with atezolizumab in patients with locally advanced or metastatic tumors, enrolled more than 550 patients across the 24 expansion cohorts by the end of 2019. Exelixis expects to present data from the metastatic castration-resistant prostate cancer (mCRPC) cohort of the trial at the ASCO (Free ASCO Whitepaper) Genitourinary Cancers Symposium in February 2020, and from the non-small cell lung cancer (NSCLC) cohort when data have matured and at the appropriate time in 2020. Based on regulatory feedback from the U.S. Food & Drug Administration (FDA) and if supported by the data from the mCRPC expansion cohorts, Exelixis intends to file with the FDA for accelerated approval in an mCRPC indication as early as 2021.
CheckMate 040, EXAMINER, and CANTATA: BMS and Exelixis expect that results of a cohort from the phase 1/2 CheckMate 040 trial investigating the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced HCC will be presented at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium in January 2020. In addition, the PFS results for the medullary thyroid cancer EXAMINER trial, which compares the 140 mg capsule formulation with the 60 mg tablet formulation of cabozantinib, are expected in 2020. Finally, Calithera expects the analysis of CANTATA, a randomized phase 2 pivotal study of cabozantinib plus glutaminase inhibitor telaglenastat (CB-839) versus cabozantinib in previously treated RCC patients, to take place in the second half of 2020. CANTATA completed enrollment in October 2019 and is sponsored by Calithera; Exelixis provides cabozantinib for the trial.
Based on the milestones for trial enrollment and data readout, and if supported by the results, the current pivotal trials could support regulatory filings for cabozantinib in various additional tumor types and settings beginning in 2020.

Anticipated New Pivotal Trials in 2020

In 2020, based on emerging data from the COSMIC-021 trial, Exelixis and its collaboration partner Roche expect to initiate three new pivotal trials of cabozantinib in combination with atezolizumab under the companies’ expanded clinical development collaboration announced on December 19, 2019. The clinical program, which Roche and Exelixis will co-fund, is expected to include three phase 3 pivotal trials in advanced NSCLC, mCRPC and RCC. Additional details will be provided when the individual trials are initiated.

Additional Clinical Updates

COSMIC-021: In late 2020, Exelixis anticipates completing enrollment in COSMIC-021, which currently includes a total of 24 expansion cohorts and a projected target enrollment of up to 1,700 patients, pending the initiation of additional cohorts or expansion of selected existing cohorts. Since its initiation in 2017, data from COSMIC-021 have been instrumental in guiding Exelixis’ clinical development strategy for cabozantinib plus ICIs, including supporting the initiation of COSMIC-312 and the additional future trials described above.
COSMIC-313: Exelixis expects to complete enrollment for COSMIC-313, the phase 3 pivotal trial evaluating the triplet combination of cabozantinib, nivolumab and ipilimumab versus the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk RCC, in early 2021 and to report top-line results of the event-driven analyses from the study in the 2022 timeframe.
XL092: The dose escalation phase 1 trial for this next generation MET, AXL and VEGFR targeting tyrosine kinase inhibitor is ongoing, and Exelixis anticipates that dose expansion cohorts and potential combination cohorts with ICIs will begin to enroll in 2020.
Anticipated Discovery Milestones in 2020

Exelixis and its partners are currently advancing three compounds through preclinical development. If the data are supportive, Exelixis believes there is the potential for these compounds to reach Investigational New Drug (IND) filing status before the end of 2020. The programs are anticipated to include both small molecules (a CDK7 inhibitor and a TAM kinase inhibitor) and a next generation antibody-drug conjugate targeting tissue factor. In addition, multiple development candidates from internal and collaborative efforts are expected to reach preclinical development in 2020, and Exelixis believes these candidates have the potential to move into clinical trials starting in 2021.

Preliminary Fourth Quarter and Full Year 2019 Financial Results

Exelixis is providing the following unaudited preliminary 2019 financial results:

Total revenues for 2019 are approximately $972 million for the full year and approximately $245 million for the fourth quarter 2019.
Net product revenues for 2019 are approximately $765 million for the full year and approximately $200 million for the fourth quarter 2019.
Research and development expenses for 2019 are approximately $340 million for the full year and approximately $98 million for the fourth quarter 2019.
Selling, general and administrative expenses for 2019 are approximately $230 million for the full year and approximately $60 million for the fourth quarter 2019.
Cash and investments at year-end 2019 were approximately $1.4 billion.
The preliminary 2019 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Full Year 2019 Financial Results are planned for release after market on Wednesday, February 26, 2020.

2020 Financial Guidance

Exelixis is providing the following financial guidance for 2020:

Total revenues are expected to be between $850 million and $900 million.
Net product revenues from the cabozantinib franchise (COMETRIQ and CABOMETYX) are anticipated to be between $725 million and $775 million, reflecting the continued evolution of the metastatic RCC and HCC treatment landscapes.
Cost of goods sold are expected to be between 4 percent and 5 percent of net product revenues.
Research and development expenses are expected to be between $460 million and $500 million corresponding with the expected initiation and completion of numerous late-stage cabozantinib trials as outlined previously and are expected to include non-cash expenses related to stock-based compensation expense of $25 million.
Selling, general and administrative expenses are expected to be between $230 million and $250 million with the continued commercial investment in CABOMETYX and the broader organization and are expected to include non-cash stock-based compensation expense of $30 million.
Guidance for the effective tax rate in 2020 is between 20 percent and 22 percent.
Cash and investments at year end 2020 are expected to be in the $1.5 billion to $1.6 billion range, reflecting our continued focus on balancing the appropriate level of investment in the business with a continued emphasis on generating free cash flow. Importantly, this cash guidance does not include any potential new business development activity, which remains a key priority for Exelixis as we continue to build toward becoming a multi-product oncology company.
Presentation and Webcast

Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company’s preliminary fourth quarter and full year 2019 financial results, 2020 financial guidance, and key priorities and milestones for 2020-21 during the company’s presentation at the J.P. Morgan Healthcare Conference beginning at 4:30 p.m. PT on Tuesday, January 14, 2020.

To access the webcast link, log onto www.exelixis.com and proceed to the News & Events / Event Calendar page under the Investors & Media heading. Please connect to the company’s website at least 15 minutes prior to the presentation to ensure adequate time for any software download that may be required to listen to the webcast. A replay will also be available at the same location for 14 days