Exelixis (NASDAQ:EXEL) executives told investors that 2025 was a “transformational year” marked by continued growth in the company’s cabozantinib franchise and accelerating preparations for a potential second oncology franchise built around zanzalintinib. Management emphasized a strategy focused on building multiple solid-tumor oncology “franchises” across products, tumor indications, and modalities, anchored by cabozantinib and expanded through late-stage development of zanzalintinib and a broader early-stage pipeline.
Cabozantinib franchise delivered revenue growth in 2025
President and CEO Mike Morrissey said the cabozantinib business posted strong performance in the fourth quarter and full year, with CABOMETYX maintaining leadership as the top tyrosine kinase inhibitor (TKI) in renal cell carcinoma (RCC) and the market leader for oral second-line-plus neuroendocrine tumors (NETs). For full-year 2025, U.S. cabozantinib franchise net product revenues increased 17% to approximately $2.12 billion compared with 2024. Fourth-quarter U.S. cabozantinib franchise net product revenues rose 6% year over year to $547 million.
Fourth-quarter results: revenue, profitability, and balance sheet
Chief Financial Officer Chris Senner reported total revenues of approximately $599 million in the fourth quarter of 2025, including cabozantinib franchise net product revenues of $546.6 million. CABOMETYX net product revenues were $544.7 million. The quarter also included about $52.8 million in royalties from partners Ipsen and Takeda on their cabozantinib sales.
Gross-to-net for the cabozantinib franchise in the fourth quarter was 28.5%, which Senner said was lower than the third quarter, primarily due to lower Public Health Service (PHS) and 340B volume. Looking ahead, the company estimated full-year 2026 gross-to-net of 31% to 32%. Senner noted Exelixis has been designated a “specified small manufacturer,” requiring a 2% discount in 2026 on all Medicare Part D sales, which is included in the company’s gross-to-net outlook.
Operating expenses (excluding restructuring expenses) were approximately $363 million in the fourth quarter, up from $341 million in the third quarter, driven mainly by higher manufacturing costs for development candidates, NDA filing fees, personnel expenses, and increased marketing expenses, partially offset by lower stock-based compensation.
Exelixis reported GAAP net income of approximately $244.5 million, or $0.92 per basic share and $0.88 per diluted share, for the fourth quarter. Non-GAAP net income was approximately $259.5 million, or $0.97 per basic share and $0.94 per diluted share, excluding about $15 million of stock-based compensation expense net of tax effects.
Cash and marketable securities totaled approximately $1.66 billion as of Dec. 31, 2025. During fiscal 2025, Exelixis repurchased $954 million of common stock, retiring roughly 24 million shares at an average price of $39.61. As of year-end, the company had about $590 million remaining under a $750 million repurchase authorization approved in October 2025. In the Q&A, Senner said the company’s commitment is to complete the authorization in 2026, so long as management believes the shares are undervalued.
Commercial update: CABOMETYX share gains and NET expansion
EVP of Commercial P.J. Haley said CABOMETYX remained the most prescribed TKI in RCC, the leading TKI plus immuno-oncology (IO) combination in first-line RCC, and the top oral agent in second-line-plus NETs. In a market basket Haley described as including cabozantinib, lenvatinib, axitinib, sunitinib, and pazopanib, CABOMETYX total prescriptions (TRx) gained three share points from 43% in the fourth quarter of 2024 to 46% in the fourth quarter of 2025. CABOMETYX TRx volume grew 15% year over year in the fourth quarter, outpacing the market basket’s 7% growth.
Haley said prescribers view CABOMETYX efficacy and tolerability favorably and are using the drug broadly across NET patient and tumor characteristics. He also pointed to additional opportunity to grow share in NETs, particularly in the community setting. To support that, management said it completed an expansion of its GI sales team in January, with the goal of accelerating CABOMETYX’s NET growth while also preparing for a potential zanzalintinib launch in colorectal cancer.
Zanzalintinib: NDA accepted and pivotal program expands
Executives repeatedly pointed to zanzalintinib as the company’s next potential franchise. Dana Aftab, EVP of R&D, said the FDA accepted Exelixis’ new drug application for zanzalintinib plus atezolizumab in third-line-plus colorectal cancer (CRC), with a PDUFA target action date of Dec. 3, 2026. The filing is based on the STELLAR-303 trial comparing zanzalintinib plus atezolizumab versus regorafenib in patients with non–microsatellite instability-high CRC who had received multiple prior therapies.
Aftab said STELLAR-303 has dual primary endpoints assessing overall survival in both the intention-to-treat (ITT) population and in patients without liver metastases (NLM). The trial met one of its dual primary endpoints, showing a 20% reduction in the risk of death in the ITT population at the final analysis. For the NLM population, Aftab said data showed a trend favoring the combination but were immature at the cutoff; the study is continuing to the planned final analysis for that endpoint, with top-line results expected around mid-year.
Beyond the NDA, Aftab outlined additional development plans, including the planned initiation of STELLAR-316 in CRC patients who are molecular residual disease (MRD) positive after definitive therapy, using Natera’s Signatera circulating tumor DNA test. Aftab said about 20% of patients are MRD positive following definitive therapy, with poor prognosis and no proven phase III options to prevent or delay metastatic progression. In the Q&A, she estimated the opportunity at roughly 20,000 to 25,000 patients based on Natera and public data.
Aftab also reviewed other zanzalintinib trials:
- STELLAR-311: a phase III trial of zanzalintinib versus everolimus as an initial oral therapy in neuroendocrine tumors, initiated in 2025 and proceeding on schedule.
- STELLAR-304: a pivotal trial of zanzalintinib plus nivolumab versus sunitinib in locally advanced or metastatic non-clear cell RCC, with top-line results expected around mid-year; management said positive results could support a second NDA filing.
- STELLAR-201: a single-arm phase II study in recurrent meningioma, expected to initiate around mid-year.
- Merck-led RCC program: an umbrella phase II study combining zanzalintinib with belzutifan in previously treated metastatic RCC, plus pivotal studies in clear cell RCC including LITESPARK-033, which initiated in December 2025.
Management also said it continues to pursue business development focused on late-stage assets in GU and GI oncology, with an emphasis on “back-end loaded pay-for-success” transactions.
In response to questions on policy-related items, Senner said 340B volume has been variable and the company expects continued variability in 2026, which can affect gross-to-net given the discounting in that segment. On the Medicare Part D “small manufacturer” discount, Morrissey said the exemption is tied to having a single product representing the majority of revenue and suggested Exelixis expects to remain under the threshold for a second product for “the foreseeable future,” while cautioning that it is early and dependent on launch dynamics.
About Exelixis (NASDAQ:EXEL)
Exelixis, Inc is a biotechnology company specializing in the discovery, development and commercialization of small molecule therapies primarily for the treatment of cancer. Building on a platform that leverages model organism genetics and high-throughput screening, the company focuses its research on kinase inhibitors that modulate critical signaling pathways involved in tumor growth and metastasis. Exelixis’s translational research approach aims to advance novel compounds from early-stage discovery through clinical development and regulatory approval.
The company’s most recognized products include CABOMETYX® (cabozantinib), approved for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma, and COMETRIQ® (cabozantinib) for metastatic medullary thyroid cancer.
