On January 08, 2023 Exelixis, Inc. (Nasdaq: EXEL) reported its preliminary unaudited financial results for the fourth quarter and full year 2022, provided financial guidance for full year 2023, and delivered an update on its business. Exelixis expects 2023 to be a year of significant growth and execution as it continues to expand and develop its pipeline of promising biotherapeutics and small molecules and pursues potential near-term label-expansion opportunities for CABOMETYX (cabozantinib) (Press release, Exelixis, JAN 8, 2023, View Source [SID1234626058]).

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!

Preliminary Fourth Quarter and Full Year 2022 Financial Results & 2023 Financial Guidance

Exelixis is providing the following preliminary unaudited 2022 financial results and financial guidance for 2023:

Fourth Quarter 2022

Full Year 2022

Full Year 2023 Guidance

Total revenues

~ $415 million

~ $1,600 million

$1,775 million – $1,875 million

Net product revenues

~ $375 million

~ $1,400 million

$1,575 million – $1,675 million

Cost of goods sold

~ 4.1%

~ 4.1%

4.0% – 5.0%

Research and development expenses

~ $340 million (1)

~ $895 million(2)

$1,000 million – $1,050 million(3)

Selling, general and administrative expenses

~ $120 million(4)

~ $460 million(5)

$475 million – $525 million(6)

Effective tax rate

n/a(7)

n/a(7)

20% – 22%

(1) Includes $10 million of non-cash stock-based compensation expense.

(2) Includes $45 million of non-cash stock-based compensation expense.

(3) Includes $45 million of non-cash stock-based compensation expense.

(4) Includes $15 million of non-cash stock-based compensation expense.

(5) Includes $62 million of non-cash stock-based compensation expense.

(6) Includes $55 million of non-cash stock-based compensation expense.

(7) Preliminary results not yet available.

The preliminary 2022 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Full Year 2022 Financial Results are planned for release after market on Tuesday, February 7, 2023.

"In 2023, Exelixis is advancing our diverse, high-impact pipeline of small molecule and biologic agents for oncology fueled by the continued growth of the cabozantinib commercial franchise," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "We expect to report data from two pivotal trials of cabozantinib, initiate the next wave of phase 3 studies of zanzalintinib (XL092), advance XB002 into full development and add new agents to our portfolio from internal discovery and collaborative efforts. Importantly, we’ll continue to pursue additional in-licensing and strategic opportunities to enhance the breadth and depth of our pipeline so that we can make an even greater impact on our mission to help cancer patients recover stronger and live longer."

Anticipated Pipeline Milestones

Exelixis made significant progress in establishing the potential of and adding new assets to the company’s pipeline in 2022. In 2022, Exelixis presented data sets for: zanzalintinib (XL092), its next-generation oral tyrosine kinase inhibitor; XB002, its most advanced antibody-drug conjugate (ADC); and XL102, a selective and irreversible cyclin-dependent kinase 7 (CDK7) inhibitor. Three promising biotherapeutics, XB010, XB014 and XB628, from internal discovery efforts are currently being evaluated in preclinical development, and collaborations were initiated with Cybrexa Therapeutics (Cybrexa) and Sairopa B.V. (Sairopa) to advance the CBX-12 and ADU-1805 programs, respectively, which were the subject of exclusive clinical option and license agreements signed in the fourth quarter of 2022.

Expansion of pivotal trial program for zanzalintinib: In 2023, Exelixis plans to expand the phase 3 development program for zanzalintinib (XL092) with multiple new phase 3 pivotal trial initiations of zanzalintinib in combination with several immuno-oncology (IO) therapies. In 2022, Exelixis initiated STELLAR-303, which evaluates zanzalintinib in combination with atezolizumab versus regorafenib in patients with colorectal cancer (CRC) that is not microsatellite instability-high or mismatch repair-deficient, who have progressed after or are intolerant to the current standard of care, as well as STELLAR-304, which evaluates zanzalintinib in combination with nivolumab versus sunitinib in patients with advanced non-clear cell renal cell carcinoma. As previously stated, Exelixis intends to develop zanzalintinib in novel combination regimens in a broad array of future potential indications, including those where cabozantinib has demonstrated anti-tumor activity.

Advancement of the XB002 JEWEL development program: In 2023, Exelixis intends to accelerate the development of XB002, its next-generation tissue factor-targeting ADC, both as a monotherapy and in combination with IO and other targeted therapies, across a wide range of tumor types. The dose-escalation stage of JEWEL-101, the first-in-human phase 1 study evaluating XB002 as a single agent and in combination with nivolumab, is ongoing and the company expects to initiate the cohort expansion stage of the study after the recommended dose and/or the maximum-tolerated dose for XB002 have been determined, as well as advance additional combination cohorts in the study to identify sensitive tumor types. Anticipated tumor cohorts across the trial include forms of non-small cell lung, ovarian, cervical, urothelial, squamous cell head and neck, pancreatic, esophageal, prostate, and breast. In October 2022, Exelixis presented promising initial results from the ongoing dose-escalation stage of JEWEL-101, demonstrating that XB002 was well-tolerated across multiple dose levels with a pharmacokinetic analysis supporting the ability of XB002 to remain stable after infusion with low levels of free payload in circulation. The company expects to move into full development by year-end.

Advancement of the XL102 QUARTZ development program: In 2023, Exelixis intends to advance the first-in-human QUARTZ-101 phase 1 trial evaluating XL102, its potent, selective, irreversible and orally bioavailable small molecule CDK7 inhibitor into the cohort expansion and potential combination cohorts. The phase 1 QUARTZ-101 study is evaluating the safety, tolerability, pharmacokinetics, anti-tumor activity and effect on biomarkers of XL102 administered alone and in multiple combination regimens in patients with advanced solid tumors. In December 2022, Exelixis presented initial dose-escalation results from the QUARTZ-101 study, demonstrating that XL102 was well-tolerated at evaluated dose levels with a pharmacokinetic analysis showing rapid absorption of XL102 and an elimination half-life of 5-9 hours. Exelixis expects to evaluate the anti-tumor activity and efficacy of XL102 in additional patients in the single-agent dose-escalation cohorts, in the tumor-specific cohort-expansion stage and in planned combination cohorts. In the cohort-expansion stage of QUARTZ-101, XL102 will be evaluated in patients with certain types of ovarian, breast and prostate cancers.

Advancement of CBX-12 clinical program in collaboration with Cybrexa: Exelixis expects its partner Cybrexa to continue to advance its phase 1 clinical study program for CBX-12 throughout 2023, including dose-expansion cohorts. CBX-12 is a clinical-stage, first-in-class peptide-drug conjugate that utilizes Cybrexa’s proprietary alphalex technology to enhance delivery of exatecan to tumor cells. It is designed to increase the therapeutic index of topoisomerase I inhibition by delivering exatecan, a highly potent, second-generation topoisomerase I inhibitor, directly to the tumor cells using a target independent approach activated by the acidic microenvironment of solid tumors. Under the terms of the agreement announced in November 2022, Exelixis has the option to acquire CBX-12 upon evaluation of a pre-specified clinical data package that includes certain phase 1 results.

Planned Investigational New Drug (IND) filing for ADU-1805 program, in collaboration with Sairopa: In the first quarter of 2023, Exelixis expects its partner Sairopa to file an IND for ADU-1805, a potential best-in-class monoclonal antibody targeting SIRPα to block the SIRPα–CD47 checkpoint. Blocking SIRPα has the potential to improve the immune system’s ability to attack tumors by addressing a significant immune-suppressive component of the tumor microenvironment. ADU-1805 is active against all human alleles of SIRPα, which may allow it to address a broader patient population than other SIRPα-directed therapies, and has been optimized to bind preferentially to SIRPα vs. other SIRP family members, which may enhance its ability to stimulate immune cells. Under the terms of the clinical development and option agreement announced in November 2022, Exelixis has the option to obtain an exclusive, worldwide license to develop and commercialize ADU-1805 and other anti-SIRPα antibodies upon review of data from prespecified phase 1 clinical studies of ADU-1805 to be completed by Sairopa during the option period.

Advancement of Development Candidates (DCs) XB010 and XB014 toward IND filing: In 2023, Exelixis plans to advance XB010, the first custom ADC generated through the company’s biotherapeutics network of collaborations, and XB014, the company’s first bispecific antibody designated as a DC in August 2022, through preclinical development and IND-enabling studies, toward potential IND filings in early 2024. XB010 targets the oncofetal antigen 5T4, which is overexpressed on a broad array of solid tumors including non-small cell lung cancer, head and neck squamous cell carcinomas, and gastric and breast carcinomas, and utilizes the SMARTag site specific conjugation platform from Catalent, Inc. to produce a homogeneous ADC with a defined drug-antibody ratio coupled to a high affinity antibody Exelixis sourced from Invenra, Inc. (Invenra). XB014 consists of a bispecific antibody, with a PDL1 targeting arm along with a CD47 targeting arm to block a macrophage checkpoint, also developed through Exelixis’ collaboration with Invenra.

DC designation for XB628: Today, Exelixis announced it has designated XB628 as its latest DC and plans to advance the program through preclinical development in 2023, toward a potential IND filing in 2024. Comprising a PDL1 targeting arm and an NKG2A targeting arm, XB628 is the company’s second bispecific antibody program developed through its collaboration with Invenra.

Discovery Expansion and Anticipated Milestones

In 2022, Exelixis enhanced the capacity and capabilities of its small molecule discovery efforts and utilized its broad collaboration network to build a differentiated biotherapeutics platform focused on the identification and optimization of next-generation ADCs, bispecific antibodies and other biologics with promising preclinical activity. In 2023, Exelixis is advancing more than 10 discovery programs through internal and collaborative efforts and expects to progress up to five new development candidates into preclinical development, encompassing multiple modalities and mechanisms across small molecules and biotherapeutics.

Anticipated Cabozantinib Milestones

"In the ten years since its initial FDA approval, cabozantinib has evolved from an orphan indication to a global oncology franchise that benefits tens of thousands of patients annually," said Michael M. Morrissey, Ph.D., President and Chief Executive Officer, Exelixis. "In 2022, cabozantinib generated approximately $1.4 billion in preliminary U.S. net product revenues, further reinforcing its status as a leading therapy for forms of renal, liver, and thyroid cancer. We’re committed to maximizing cabozantinib’s clinical and commercial potential – including through the ongoing CONTACT clinical trials, which represent the final Exelixis-sponsored pivotal trials of the compound – as our pipeline buildout proceeds."

Pivotal trial progress and data readouts anticipated in 2023: During the first half of the year, Exelixis expects to report top-line results for the progression-free survival endpoint from CONTACT-03, the phase 3 pivotal trial sponsored by Roche evaluating the combination of cabozantinib and atezolizumab versus cabozantinib monotherapy in a form of renal cell carcinoma (RCC) in patients who progressed during or following treatment with an immune checkpoint inhibitor as the immediate preceding line of therapy. In the second half of the year, the company anticipates completion of enrollment and expects to report top-line results for the progression-free survival endpoint for CONTACT-02, the phase 3 pivotal trial sponsored by Exelixis evaluating the combination of cabozantinib and atezolizumab in patients with metastatic castration-resistant prostate cancer who have been previously treated with one novel hormonal therapy. Also expected in 2023 is the next overall survival analysis from 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.

Cabozantinib Abbreviated New Drug Application (ANDA) Litigation: The United States District Court for the District of Delaware has scheduled a second bench trial for Exelixis’ ongoing ANDA lawsuit against MSN Pharmaceuticals, Inc. for October 2023. Exelixis is confident in its cabozantinib patent estate and will vigorously defend the patents at issue.

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 2022 financial results, 2023 financial guidance, and key priorities and milestones for 2023 during the company’s presentation at the J.P. Morgan Healthcare Conference beginning at 8:15 p.m. ET / 5:15 p.m. PT on Monday, January 9, 2022.

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 at least 30 days.