Zanzalintinib

– The FDA assigned a Prescription Drug User Fee Act target action date of December 3, 2026 – – Application is based on results from the phase 3 STELLAR-303 pivotal trial, in which zanzalintinib in combination with atezolizumab improved median overall survival and significantly reduced the risk of death versus regorafenib in the intention-to-treat population – ALAMEDA, Calif. --(BUSINESS WIRE)--Feb. 2, 2026-- Exelixis, Inc. (Nasdaq: EXEL) today announced that its New Drug Application (NDA) for zanzalintinib, in combination with atezolizumab (Tecentriq®), has been accepted for review in the U.S. for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, and, if RAS wild-type, an anti-epidermal growth factor receptor (EGFR) therapy. The Food and Drug Administration (FDA) assigned a standard review with a Prescription Drug User Fee Act target action date of December 3, 2026 . “We are encouraged by this meaningful progress toward addressing the needs of patients with previously treated metastatic colorectal cancer, for whom effective therapies have been limited and treatment outcomes remain poor,” said Dana T. Aftab , Ph.D., Executive Vice President, Research and Development , Exelixis . “Zanzalintinib has the potential to become an important advancement in a challenging treatment landscape, and if approved, zanzalintinib in combination with atezolizumab would provide a novel mechanism of action for patients with previously treated metastatic colorectal cancer. We are deeply grateful to the patients, caregivers and investigators contributing to the clinical research in support of this application, and we look forward to collaborating with the FDA during the review process for our first NDA for zanzalintinib.” The NDA is based on the results of the phase 3 STELLAR-303 pivotal trial, in which zanzalintinib in combination with atezolizumab demonstrated a statistically significant improvement in overall survival (OS) versus regorafenib in the intention-to-treat (ITT) population of patients with previously treated CRC. Detailed results, including OS and progression-free survival (PFS) in the ITT population and in the subset of patients without liver metastases (non-liver metastases, NLM), were presented at the 2025 European Society for Medical Oncology (ESMO) Congress and published in The Lancet . Data pertaining to the other dual primary endpoint, OS in patients without active liver metastases, were immature at the data cutoff, and the trial is proceeding to the planned final analysis for this endpoint, which is expected in mid-2026, based on current event rates. About STELLAR-303 STELLAR-303 (NCT05425940) is a global, multicenter, randomized, phase 3, open-label study that randomized patients 1:1 to either zanzalintinib in combination with atezolizumab (n=451) or regorafenib (n=450). 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. 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. Secondary endpoints include PFS, 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 novel oral kinase inhibitor that inhibits the activity of the TAM kinases (TYRO3, AXL, MER), MET and VEGF receptors. These kinases play important roles in oncogenic processes, including tumor cell proliferation, metastasis, angiogenesis, drug resistance and evasion of antitumor immunity. 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 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 a leading cause of cancer-related deaths in the U.S. 1 Approximately 159,000 new cases will be diagnosed in the U.S. in 2026, with around 55,000 expected deaths from the disease.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 around just 15%.1,2 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 and biotherapeutics. This comprehensive approach harnesses decades of robust investment in our science and partnerships to advance our pipeline of franchise molecules, including our novel oral kinase inhibitor zanzalintinib, and to 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. Forward-Looking Statements This press release contains forward-looking statements, including, without limitation, statements related to: the therapeutic potential of zanzalintinib, in combination with atezolizumab, as a treatment for patients with previously treated mCRC; the regulatory review process, including the PDUFA target action date assigned by the FDA, and Exelixis’ plans to collaborate with the FDA while the application is reviewed; and Exelixis’ scientific pursuit to create transformational treatments that give patients more hope for the future. Any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements and are based upon Exelixis’ current plans, assumptions, beliefs, expectations, estimates and projections. Forward-looking statements involve risks and uncertainties. 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: complexities and the unpredictability of the regulatory review and approval processes in the U.S. and elsewhere, including the risk that the FDA may not approve the combination of zanzalintinib with atezolizumab as a treatment for patients with previously treated mCRC in a timely fashion, if at all; unexpected concerns that may arise as a result of the occurrence of adverse safety events or additional data analyses of clinical trials evaluating zanzalintinib and/or atezolizumab; Exelixis’ ability to protect its intellectual property rights; market competition; changes in economic and business conditions; and other factors affecting the ability of Exelixis to obtain regulatory approval for zanzalintinib in new indications detailed from time to time under the caption “Risk Factors” in Exelixis’ most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, and in Exelixis’ future filings with the Securities and Exchange Commission. All forward-looking statements in this press release are based on information available to Exelixis as of the date of this press release, and Exelixis undertakes no obligation to update or revise any forward-looking statements contained herein, except as required by law. Exelixis , the Exelixis logo and CABOMETYX are registered U.S. trademarks of Exelixis . TECENTRIQ is a registered U.S. trademark of Genentech , a member of the Roche Group. View source version on businesswire.com: https://www.businesswire.com/news/home/20260130221586/en/ Investors Contact: Andrew Peters SVP, Strategy and Investor Relations Exelixis, Inc. 650-837-7248 apeters@exelixis.com Media Contact: Stekki Millman Senior Director, Public Affairs Exelixis, Inc. 650-837-7187 smillman@exelixis.com Source: Exelixis, Inc.

Exelixis CEO Michael Morrissey, Ph.D., said he\'s carefully evaluating whether the company would expand outside the U.S.\n Exelixis may only have one drug on the market right now, but with phase 3 results for a potential new blockbuster on the horizon and a growing pipeline, the Cabometyx maker is aiming big. Specifically, the drugmaker intends to become a top 5 solid tumor company by U.S. sales.“It’s all about building franchises,” Exelixis CEO Michael Morrissey, Ph.D., said in an interview with Fierce on the sidelines of the J.P. Morgan Healthcare Conference in San Francisco. “It’s all about having the mindset that you’re not going to do one compound for one indication, because the economy of scale doesn’t work,” he added.Since its first FDA approval more than 13 years ago in medullary thyroid cancer, cabozantinib—sold as Cabometyx and Cometriq—has been Exelixis’ sole approved drug, driving $2.1 billion in U.S. revenues in 2025, according to a preliminary calculation the company unveiled at JPM. Cabozantinib alone has put the California company at No. 10 on the U.S. solid tumor rankings by sales.Morrissey described cabozantinib as a “franchise molecule,” having recently added its sixth and seventh indications in pancreatic and extra-pancreatic neuroendocrine tumors (NETs), respectively.Now, Exelixis hopes to repeat the success with zanzalintinib, which the company considers “the foundation of future oncology franchises” with the potential to reach $5 billion in peak annual sales. The company has just filed the next-generation TKI with the FDA for use alongside Roche’s Tecentriq in previously treated metastatic colorectal cancer (mCRC). Several other phase 3 programs are either underway or being planned for earlier stages of disease and in other tumor types. Zanzalintinib’s first phase 3 readout was not exactly the most exciting outcome that doctors were hoping for. The phase 3 Stellar-303 study linked zanzalintinib to a 20% reduction in the risk of death compared with Bayer’s Stivarga in patients with previously treated mCRC, meeting one of its dual primary endpoints. Patients’ median overall survival was improved by 1.5 months to 10.9 months with the investigational therapy. That limited magnitude of improvement, combined with an increase in grade 3 or higher adverse events, raised a question around whether the combo could be the new standard of care.The answer to that question is partly dependent on the final analysis of the trial’s other primary endpoint, OS in a subgroup of patients without liver metastases, which Exelixis expects to read out mid-2026.Despite the modest showing in the study, Morrissey noted that doctors have wanted to use an immunotherapy-based regimen for late-line colorectal cancer, and that Stellar-303 offers them their first hope after multiple prior pivotal trial failures within the PD-1/L1 class.As for the non-liver metastases population, Morrissey noted that data were getting close to statistical significance at the last analysis. He acknowledged that showing an OS improvement in the subgroup is important “from a marketing point of view” when educating doctors about zanzalintinib’s overall profile, but added that “it’s not a must-have.”In any case, the bigger fight is not in late-line mCRC. Instead, earlier treatment settings and expansions into other tumor types will be key to zanzalintinib’s success.“We’re moving up,” Morrissey said, referring to the company’s efforts earlier in the treatment sequence.Exelixis recently reached a collaboration with diagnostic company Natera, which will provide a ctDNA assay to identify patients with resected stage 2/3 CRC who have completed definitive therapy but still have molecular residual disease (MRD) to enroll in the phase 3 Stellar-316 trial. This is a high-risk population who likely will progress to metastatic disease within about six months to nine months after surgery and adjuvant chemotherapy, Morrissey noted.Using its ctDNA assay to detect MRD, Natera recently helped Roche turn a previous failure in a broad group of muscle-invasive bladder cancer patients into a phase 3 win in a selective MRD-positive trial population.Partnering with Natera could also save Exelixis some effort when selecting trial sites.“They’ve been screening patients for years,” Morrissey said. “So they know the institutions that use it well, they know the investigators that use it a lot, and they know what patients are already MRD-positive. So it’s the ideal setup to be able to lock and load.”CRC is only piece of the zanzalintinib puzzle. Another major opportunity for the TKI lies in kidney disease, for which Exelixis has formed a clinical development partnership with Merck & Co. In December, Litespark-033, the first Merck-sponsored pivotal trial under the collaboration, kicked off to evaluate zanzalintinib and Merck’s Welireg. A second phase 3 is being planned.In another major milestone expected this year, the phase 3 Stellar-304 study pitting zanzalintinib and Bristol Myers Squibb’s Opdivo against Pfizer’s Sutent in previously untreated patients with advanced non-clear cell renal cell carcinoma is expected to read out mid-2026. Collaborating with the competitionExelixis already knows how to work with Big Pharma through Cabometyx, which Morrissey said highlights the idea of collaborating with the competition. Opdivo was once Cabometyx’s biggest competition in kidney cancer until the CheckMate-9ER trial showed the power of combining the two agents. Results from that trial helped drive a 2.5-fold increase in Cabometyx’s revenue in the ensuing five years, Morrissey said.Exelixis’ franchise-in-a-molecule plan for zanzalintinib includes other tumor types, although Morrissey is letting data determine the biggest indication.“Our job is to do the right selection and the right prioritization and then execute at the highest level, and then the data will tell us where to go,” he said.Even with blockbuster sales pegged to their names, the two TKIs might not be enough to get Exelixis into the “top 5” spot, especially considering that cabozantinib is expected to face generics at the beginning of 2031.“We probably need more,” Morrissey said.The CEO, for now, also wouldn’t pick a potential third pillar of the company following zanzalintinib. Exelixis’ earlier-stage pipeline includes antibody-drug conjugates targeting DLL3, 5T4 and tissue factor; a PD-L1xNKG2A bispecific; and molecular glue and degraders targeting KRAS.On the commercial side, Exelixis has been building out its gastrointestinal cancer sales force following Cabometyx’s NET approvals in March 2025. The hope is that the same sales force can cover zanzalintinib in CRC, too, although Morrissey recognized that the timing of the back-to-back launches may be tight.“Those are good problems to have if you have to scale the organization, because you’re so successful clinically,” Morrissey said.But seemingly running counter to a potential business expansion and its lofty corporate aspirations, Exelixis recently launched a reorganization that includes winding down a site in Pennsylvania and 130 layoffs. Morrissey described the overhaul as the final move in his push to implement a back-to-office policy after the pandemic. RELATED: UPDATED: Exelixis to lay off 130 employees, shut down Pennsylvania site in post-pandemic downsizing “It concentrates all of our critical mass and all of our brain power in Alameda, [California],” Morrissey said.While the satellite operation outside of Philadelphia and its big remote workforce “worked okay,” it “wasn’t nearly as effective” as people working together in the same office, the CEO observed.Exelixis first unveiled the goal to become a “top 5 solid tumor oncology company” during an R&D event in December. During his interview with Fierce, Morrissey put a “U.S.” parameter around that goal because the company has so far relied on partners to handle ex-U.S. markets, including Ipsen in Europe and Takeda in Japan. As the company grows, will it look to build a global footprint?“We’re looking at that very carefully right now,” Morrissey said. “We’re really analyzing all the options that we have relative to ex-U.S. We have deep expertise, and our commercial organization in the U.S. competes with Big Pharma every single day very effectively. So, we’re obviously going to really retrench in the U.S., and then look carefully at how we operationalize the rest of the world.”