Exelixis (NASDAQ:EXEL) detailed its commercial momentum for cabozantinib and outlined key upcoming clinical catalysts for zanzalintinib during a discussion at the Citizens Life Sciences Conference featuring Andrew Peters.
Cabozantinib performance and 2026 outlook
Peters said 2025 was “an exciting year” for the company, citing continued execution across its commercial and development organizations and the delivery of the first pivotal data from its “zanza” program. He emphasized that cabozantinib remains central to Exelixis’ business, noting that Cabometyx has been approved in seven indications.
Neuroendocrine tumors: a “billion-dollar” oral segment
On the NET opportunity, Peters said the indication was approved “at the end of March last year,” making the company “almost a year from the launch.” He described NETs as an area that has been “underappreciated” historically, both by investors and by the pharmaceutical industry, and said Exelixis sees a broader opportunity that spans Cabometyx, zanzalintinib, and an SSTR2 program.
He said Exelixis has discussed an estimated $1 billion market for the “oral segment” in NETs when applying “contemporary pricing and contemporary duration,” noting that before cabozantinib the segment was “really a generics market.” He added that uptake can be shaped by the disease’s often indolent nature, with patients potentially staying on prior therapies for extended periods before considering new options. Exelixis’ stated goal is to penetrate as much of that segment as possible.
Peters also said the company increasingly views its business through both molecule-based and indication-based “franchises,” with an aim to establish a presence for its compounds in RCC, colorectal cancer (CRC), and NETs. He said Exelixis wants to be a market leader in NETs in the same way it views itself in RCC, and he expressed the company’s ambition to grow into a leadership position in CRC as well.
RCC competition: LITESPARK data and the sequencing debate
Asked about Merck’s LITESPARK-011 data and whether it could threaten cabozantinib monotherapy in second-line RCC, Peters said feedback from clinicians has pointed to overall survival as a key determinant of where combinations fit in treatment. He framed the decision as a common oncology question—whether to combine mechanisms or sequence them—and argued that a survival advantage is particularly important when combining therapies because sequencing can preserve optionality.
He compared the progression-free survival (PFS) benefit observed in the combination with what he described as a reasonable expectation from sequencing (a second-line TKI followed by belzutifan), and he noted that combining agents can add toxicity. He cited discontinuation dynamics from the study—stating that roughly 40% of patients discontinued one of the two agents, with about 20% discontinuing each drug—resulting in a meaningful portion of patients effectively receiving monotherapy.
Peters also pointed to the “TKI break” dynamic he said has helped drive belzutifan use, describing it as a way for patients who have been on IO/TKI therapy for extended periods to switch to an active RCC mechanism with a different side effect profile. Overall, he said the data update appeared “not practice-changing” and suggested it was “probably a net slight positive” for Exelixis, arguing that some physicians who choose a lenvatinib/belzutifan approach in second line may be more inclined to use cabo/nivo in the front line to avoid repeating lenvatinib.
Discussing earlier-stage studies such as LITESPARK-021 and adjuvant dynamics, Peters reiterated that the benefit-risk tradeoff and the need for survival data become even more important earlier in the patient journey, especially when patients may be functionally cancer-free in the adjuvant setting.
Zanzalintinib: breadth of program and near-term milestones
Peters addressed Exelixis’ prior comment that zanzalintinib could represent a $5 billion opportunity, saying the company aimed to highlight the breadth of the program and its belief that zanzalintinib can be “bigger than cabo.” He said the clinical program has expanded and now includes seven pivotal studies, adding that the opportunity is not driven by any single indication. He described the growth strategy as spanning both genitourinary (GU) and gastrointestinal (GI) oncology, which he said were roughly “50/50” in that market build, and highlighted the addition of an earlier CRC study, STELLAR-316, as one the company is “particularly excited about.”
In late-line colorectal cancer, Peters discussed STELLAR-303 (zanzalintinib plus atezolizumab). He said Exelixis’ market research suggests the U.S. third-line-plus segment is about $1.5 billion in total and described it as fragmented, with approximately:
- One-third in the SUNLIGHT regimen
- One-third in TKIs
- One-third in chemotherapy and other treatments
He said the company is seeing “quite a bit of enthusiasm” ahead of a potential December PDUFA date, in part because the study was “the first to be successful” in bringing a checkpoint inhibitor-containing regimen to this patient population, and contrasted it with Merck’s LEAP-017 (lenvatinib plus pembrolizumab), which he said was unsuccessful in a similar population. Peters emphasized the commercial appeal of a “chemo-free,” checkpoint-containing regimen that showed a survival advantage over standard of care, and he noted that prior bevacizumab use can complicate interpretation and use of SUNLIGHT based on differences seen in its data.
On remaining STELLAR-303 data for overall survival in the non-liver metastases subgroup, Peters said it is not gating, emphasizing that the presented and published results reflected the intent-to-treat population and that benefit was observed across subtypes including liver metastases status and prior bevacizumab exposure. He added that demonstrating statistically robust benefits across subgroups would strengthen the commercial message.
Peters also discussed STELLAR-304 in non-clear cell RCC, calling it the first pivotal study run in that setting and estimating the segment at about 15% to 20% of kidney cancer patients. He said current practice is based on limited single-arm data with wide confidence intervals and no dominant standard, and that Exelixis aims to generate “level one evidence” for zanzalintinib plus nivolumab. He reiterated company guidance for data in the middle of the year.
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.
