Regorafenib

– Zanzalintinib in combination with atezolizumab demonstrated a statistically significant reduction in risk of death versus regorafenib in intent-to-treat population – ALAMEDA, CA, USA I June 22, 2025 I Exelixis, Inc. (Nasdaq: EXEL) today announced positive topline results from the STELLAR-303 phase 3 pivotal trial in which zanzalintinib in combination with atezolizumab (Tecentriq ® ) demonstrated a statistically significant improvement in overall survival (OS) versus regorafenib in the intent-to-treat (ITT) population of patients with previously treated non-microsatellite instability (MSI)-high metastatic colorectal cancer (CRC). These topline findings are from the final analysis conducted by the Independent Data Monitoring Committee of one of the dual primary endpoints of the STELLAR-303 phase 3 trial. The trial will proceed to the planned final analysis for the other dual primary endpoint of OS in patients without liver metastases (non-liver metastases, NLM). The safety profiles of zanzalintinib in combination with atezolizumab and of regorafenib were generally consistent with what has been previously observed, and no new safety signals were identified. The ITT population consisted of all randomized patients, regardless of the presence of liver metastases. The NLM subgroup consisted of patients who did not have active liver metastases at baseline as determined by investigator assessment. “The STELLAR-303 results, which showed a survival benefit with the combination of zanzalintinib and atezolizumab versus regorafenib across all randomized patients with previously treated metastatic colorectal cancer, marks an important first milestone for our zanzalintinib pivotal development program,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “We look forward to discussing the findings with regulatory authorities and presenting the detailed results at an upcoming medical conference.” Secondary endpoints of STELLAR-303 include progression-free survival, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. Exelixis plans to submit detailed results of STELLAR-303 for presentation at an upcoming medical conference. About STELLAR-303 STELLAR-303 (NCT05425940) is a global, multicenter, randomized, phase 3, open-label study that randomized 901 patients 1:1 to either zanzalintinib (100 mg) in combination with atezolizumab or regorafenib. The study includes patients with previously treated non-MSI-high metastatic CRC. The dual primary endpoints of the study are OS in the ITT population and in the NLM subgroup of patients. Presence of liver metastases at baseline for all enrolled patients was determined by investigator assessment. Secondary endpoints include progression-free survival, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. More information about the trial is available at ClinicalTrials.gov . About Zanzalintinib Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including colorectal cancer, kidney cancer, head and neck cancer and neuroendocrine tumors. Zanzalintinib is an investigational agent that is not approved for any use and is the subject of ongoing clinical trials. About CRC CRC is the third most common cancer and the second leading cause of cancer-related deaths in the U.S. 1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025. 1 CRC is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent. 2 Nearly a quarter of CRC cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 16.2%. 2 The liver is the most common site for CRC metastasis. Liver metastases significantly impact survival, with a median five-year survival rate of less than 14% when treated with palliative chemotherapy. 3 About Exelixis Exelixis is a globally ambitious oncology company innovating next-generation medicines and regimens at the forefront of cancer care. Powered by drug discovery and development excellence, we are rapidly evolving our product portfolio to target an expanding range of tumor types and indications with our clinically differentiated pipeline of small molecules, antibody-drug conjugates and other biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our investigational programs and extend the impact of our flagship commercial product, CABOMETYX ® (cabozantinib). Exelixis is driven by a bold scientific pursuit to create transformational treatments that give more patients hope for the future. For information about the company and its mission to help cancer patients recover stronger and live longer, visit www.exelixis.com , follow @ExelixisInc on X (Twitter), like Exelixis, Inc. on Facebook and follow Exelixis on LinkedIn. 1 Key Statistics for Colorectal Cancer. ACS website. Available at: https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html . Accessed June 2025. 2 Cancer Stat Facts: Colorectal Cancer. SEER website. Available at: https://seer.cancer.gov/statfacts/html/colorect.html . Accessed June 2025. 3 Ros J, Salva F, Dopazo C, et al. Liver transplantation in metastatic colorectal cancer: are we ready for it? Br J Cancer. May 2023;128(10):1797-1806. SOURCE: Exelixis

Exelixis said its oral third-generation tyrosine kinase inhibitor (TKI) candidate zanzalintinib in combination with Roche’s anti-PD-L1 antibody Tecentriq (atezolizumab) met the first of two overall survival (OS) goals in a pivotal study of pre-treated patients with non-microsatellite instability-high metastatic colorectal cancer. The news sent the biotech's shares up 12% in pre-market trading on Monday.The Phase III STELLAR-303 trial randomised 901 patients to receive combination treatment with zanzalintinib plus Tecentriq or monotherapy with Bayer's oral multi-kinase inhibitor Stivarga (regorafenib). Top-line results showed that the dual regimen met the first primary endpoint, demonstrating a statistically significant OS benefit over Stivarga in the intent-to-treat population — which included all randomised patients regardless of liver metastases presence. Meanwhile, safety profiles for both treatment arms remained consistent with previously observed data, with no new safety signals identified.“We look forward to discussing the findings with regulatory authorities and presenting the detailed results at an upcoming medical conference," remarked Amy Peterson, chief medical officer at Exelixis.The company noted that the trial continues towards evaluation of its second primary endpoint, which is OS in the non-liver metastases subgroup. Additionally, secondary goals, including progression-free survival, objective response rate and duration of response, are being assessed across both patient populations. Besides colorectal cancer, zanzalintinib together with various checkpoint inhibitors, is being investigated in kidney cancer, head and neck cancer and neuroendocrine tumours.