Exelixis (NASDAQ:EXEL) described its current commercial trajectory, late-stage clinical programs, and strategic priorities during a discussion at a Barclays event featuring Senior Vice President of Strategy and Investor Relations Andrew Peters. Peters emphasized that the company remains anchored by its lead product CABOMETYX (cabozantinib), while advancing a next-generation tyrosine kinase inhibitor (TKI), zanzalintinib, and a broader internal pipeline that includes both small molecules and biotherapeutics.
Commercial foundation: CABOMETYX and growth drivers
Peters said Exelixis is “a commercial oncology company” built around CABOMETYX, which he characterized as a TKI targeting VEGF as well as other kinases including MET, AXL, MER and the TAM kinases. He noted that cabozantinib has established approvals across multiple tumor types, including kidney cancer, liver cancer, thyroid cancer, and neuroendocrine tumors (NETs).
Capital allocation and the “big small company” strategy
Peters described Exelixis as a “big small company,” saying it has chosen to remain focused in solid tumors—particularly GI and GU oncology—where it sees itself as scaled and optimized. He said the company views RCC, NET, and colorectal cancer (CRC) as core areas and intends to build further around those franchises.
He also highlighted what he called a “Cabo lens,” describing it as a framework for strategic decision-making based on learnings from CABOMETYX’s commercial success. Under that approach, Peters said the company is disciplined in business development, looking for external programs that could plausibly become a new standard of care rather than incremental entrants. He added that Exelixis’ success with CABOMETYX enables investment internally and externally and supports share repurchases, saying the company believes its stock is “cheap candidly.”
RCC market dynamics: read-through from belzutifan discussions
Asked about Merck’s belzutifan data in RCC, Peters said Exelixis spent time speaking with clinicians about whether new regimens are best used in combination or sequenced. He suggested a key clinical question is whether there is an overall survival advantage and relayed feedback that sequencing can provide value by offering patients a “TKI break” after extended use of prior TKIs.
Peters said clinicians questioned whether combining therapies meaningfully improves progression-free survival (PFS) relative to sequencing, given added toxicity and the potential loss of that “TKI break.” He added that, for patients who do use a lenvatinib/belzutifan approach in second line, it could lead physicians to avoid lenvatinib-based regimens in first line—potentially benefiting CABOMETYX’s frontline share. “Net-net,” he said, the overall dynamic appeared “a little bit of a net positive for us.”
Zanzalintinib: pivotal program, CRC opportunity, and commercial preparation
Peters positioned zanzalintinib as a next-generation, optimized TKI designed to build on cabozantinib’s “core essence,” with improvements including half-life and pharmacokinetics. He said zanzalintinib is currently in seven pivotal studies, with additional studies planned, and that the program delivered its first positive pivotal data last year. Peters also noted a PDUFA date in December with the FDA.
Discussing commercialization for potential CRC use, Peters reiterated an “aspirational” goal for Exelixis to be balanced roughly 50/50 between GI and GU over time. He said the company increased the size of its commercial organization and sales force at the end of last year, specifically to maximize the NET opportunity, and that the resulting GI focus also helps prepare operationally for a potential zanzalintinib launch later this year.
On additional CRC data expected from STELLAR-303, Peters said the previously reported results reflected the intent-to-treat (ITT) population inclusive of patients with and without liver metastases, while the non-liver metastases subgroup was immature at the time of the primary analysis due to fewer events. He also said data presented at ESMO and published subsequently did not show a meaningful difference in effect size across major subgroups such as liver metastases status and prior VEGF use. Peters said the company expects updated subgroup Kaplan-Meier curves to strengthen the commercial narrative around survival outcomes.
Earlier-stage expansion: adjuvant ctDNA-positive CRC and other pipeline efforts
Peters discussed the rationale for moving into adjuvant CRC with STELLAR-316, citing emerging data on circulating tumor DNA (ctDNA) and recurrence risk. He referenced Natera’s Signatera test and said that for about “20-ish%” of patients who become ctDNA positive after definitive therapy/adjuvant treatment, recurrence risk is high and can occur in a relatively short period—around five to six months. He stated that the current approach for ctDNA-positive patients is essentially “watch and wait,” with no active intervention until progression, which he described as a significant unmet need.
He said Exelixis believes this setting presents an opportunity to identify patients likely to recur who may be sensitive to zanzalintinib and to run a placebo-controlled oncology study. Peters also highlighted an operational element: collaboration with Natera could help identify potentially eligible patients, rather than relying solely on traditional broad site screening.
In non-clear cell RCC, Peters said STELLAR-304 was designed in a setting where there has never been a randomized study, and where current utilization patterns are “all over the map” due to limited and variable evidence. He characterized the study as an opportunity to establish “level one evidence” and help define a standard of care.
On NETs, Peters contrasted the CABINET trial—which he described as a broad, cooperative group, placebo-controlled study with many later-line patients—with STELLAR-311, which compares zanzalintinib to everolimus in an earlier-line population using an active comparator. He said Exelixis expects the differences in study design and patient populations to influence future uptake dynamics in the NET market.
Finally, discussing its tissue factor antibody-drug conjugate (ADC) program, Peters addressed differentiation versus Tivdak, describing Tivdak as using more traditional MMAE linker technology. He said Exelixis’ approach includes an antibody design that is “non-competitive with Factor VII,” which he noted has implications for coagulation and bleeding risk, and said the company selected linker and warhead elements with colorectal cancer activity in mind, consistent with its franchise-based strategy.
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.
