Exelixis (NASDAQ:EXEL) President and Chief Executive Officer Michael Morrissey, PhD, outlined the biotechnology company’s oncology strategy during a Bernstein fireside chat, emphasizing a focused effort to build multiple cancer franchises around cabozantinib, zanzalintinib and a broader pipeline of small molecules and biologics.
Morrissey said Exelixis’ approach is centered on improving standards of care in cancer, particularly in genitourinary and gastrointestinal tumors. He said the company’s experience with cabozantinib has shaped its view that clinical trial success alone is not enough; a therapy must meaningfully change treatment practice to become a commercial success.
Franchise strategy remains centered on GU and GI cancers
Morrissey described Exelixis’ strategy as a “multi-franchise” model that includes product franchises, tumor franchises and modality franchises. He said the company remains focused on GU and GI cancers, while allowing some flexibility for other tumors where Exelixis sees meaningful clinical activity, including lung maintenance and meningioma within the zanzalintinib program.
He said Exelixis has deliberately avoided spreading itself too broadly, particularly in hematologic oncology, where he said competition is intense and the company did not see a clear opportunity to offer a differentiated benefit. Instead, Exelixis has concentrated resources in solid tumors where it already has clinical and commercial capabilities.
“Strategy often comes down to not really so much what you’re doing, but what you choose not to do,” Morrissey said.
Zanzalintinib positioned as next key growth driver
Morrissey said Exelixis has largely stopped investing in cabozantinib as a development asset and is now prioritizing zanzalintinib, which he described as a potential next-generation molecule. He highlighted the company’s successful STELLAR-303 trial in third-line-plus colorectal cancer, saying it improved overall survival after several checkpoint-based trials in the field had failed.
He said zanzalintinib is currently under review and described the trial as an important starting point for a broader franchise. Morrissey said Exelixis has “seven ongoing or soon-to-start pivotal trials” in the first wave of zanzalintinib development, with another wave forming.
In colorectal cancer, Morrissey pointed to STELLAR-316, which is evaluating treatment for high-risk patients after surgery and chemotherapy using Signatera technology to identify patients by minimal residual disease status. He said there is currently no standard of care for those high-risk patients after surgery and chemotherapy, calling the opportunity both scientifically and clinically motivating.
Renal cancer remains a core market
Morrissey said renal cell carcinoma remains central to Exelixis’ business, citing cabozantinib’s position as a leading tyrosine kinase inhibitor in RCC, including in frontline immunotherapy-TKI combinations and later-line settings.
For zanzalintinib, he highlighted STELLAR-304 in non-clear cell RCC in combination with nivolumab. Morrissey said no one has previously conducted a pivotal trial in that subpopulation. He also noted collaborations with Merck involving zanzalintinib and belzutifan in post-adjuvant patients and in second- and third-line-plus RCC patients.
Morrissey said improving outcomes in RCC has become more difficult as prior advances have raised the standard of care. He said future combinations must demonstrate both improved activity and acceptable tolerability to justify development.
Pipeline expands into ADCs, bispecifics and neuroendocrine tumors
Morrissey said Exelixis has four molecules in the clinic and additional candidates approaching investigational new drug applications. The early-stage pipeline includes antibody-drug conjugates, a USP1 inhibitor and the bispecific XB628, which he said the company is beginning to evaluate in combinations with zanzalintinib.
He highlighted XB371, a tissue factor-targeting ADC with a topoisomerase payload, as a molecule designed for colorectal cancer. Morrissey said the company is evaluating how such assets could combine with zanzalintinib and checkpoint inhibitors as part of a broader franchise-building strategy.
In neuroendocrine tumors, Morrissey discussed cabozantinib’s CABINET study, the ongoing STELLAR-311 trial of zanzalintinib against everolimus, and preclinical work on an oral SSTR2 antagonist. He said current somatostatin agonists are peptide-based injectable therapies and that an oral option could be meaningful for patients if successful. He also referenced DLL3 as another neuroendocrine-related target at the IND stage this year.
Financial discipline and collaborations support development plans
Morrissey said Exelixis has been profitable since around 2017 and has a strong balance sheet that allows it to invest in pivotal trials, pursue external assets and buy back shares. He said the company believes its stock is undervalued, in part because of how the market currently views zanzalintinib.
He also emphasized collaborations as an important part of Exelixis’ model, citing prior work with Bristol Myers Squibb on cabozantinib and nivolumab, including the 9ER study. Morrissey said successful partnerships require aligned goals, scientific complementarity and a shared view of what clinical success should look like.
Looking ahead, Morrissey said Exelixis will judge success by its ability to change standards of care, treat more patients and build additional franchise molecules. He described the company’s commercial, discovery, competitive intelligence and financial teams as closely integrated in deciding where to allocate capital.
“If we’re not actively changing standard of care, then we need to ask the question, what are we doing?” Morrissey said.
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.
