Exelixis Halts Tissue Factor-Targeting ADC, Favors Tivdak

Exelixis has decided to halt the development of its tissue factor (TF)-targeting antibody-drug conjugate (ADC), known as XB002, after determining that it is unlikely to outperform Pfizer and Genmab's Tivdak. Tivdak, an approved TF-focused ADC, is currently marketed for cervical cancer. Exelixis had been testing XB002 in the phase 1 JEWEL-101 trial targeting advanced solid tumors. While the company plans to reveal the trial data at a later date, preliminary insights led Exelixis to conclude that XB002 would not surpass Tivdak or other TF-targeting ADCs under development.

The resources allocated to the XB002 program will now be redirected towards more promising initiatives. Specifically, Exelixis will focus on zanzalintinib, a tyrosine kinase inhibitor in late-stage development, as well as the phase 1 USP1 inhibitor XL309 and other projects within their expanding pipeline, according to the company’s second-quarter earnings release.

However, Exelixis is not completely abandoning ADCs. The company noted that XB371, another ADC involving a topoisomerase payload linked to a TF-targeting monoclonal antibody, remains in preclinical development.

Exelixis CEO Michael Morrissey, Ph.D., highlighted Cabometyx in his statement accompanying the earnings release. Cabometyx is already approved for renal cell carcinoma, hepatocellular carcinoma, and thyroid cancer. In the second quarter, it generated $433.3 million in net U.S. revenues. Furthermore, the FDA is considering an application to approve Cabometyx for advanced neuroendocrine tumors (NETs).

“We’re actively preparing for launch and excited at the prospect of bringing this new treatment option to previously treated advanced NET patients with high unmet medical need,” Morrissey stated. “At the same time, we are prioritizing our clinical pipeline with plans to initiate a new phase 3 pivotal trial for zanzalintinib in NET, advance phase 1 efforts for XL309 and XB010, and discontinue development of XB002.”

Analysts from William Blair commented on the strategic shift, noting that Exelixis is at a critical juncture. The growth of the Cabometyx franchise is stabilizing, while pipeline programs, especially zanzalintinib, are becoming increasingly essential to offset the eventual market exclusivity expiration of Cabometyx in 2031. They also pointed out that NETs and metastatic castration-resistant prostate cancer could emerge as significant growth opportunities for the Cabometyx franchise in the midterm.

The year has been one of significant change for Exelixis. In January, the company laid off 175 employees, which is about 13% of its workforce, as part of a broader restructuring effort designed to concentrate research and development resources on advancing its emerging pipeline. At that time, the strategy included progressing XB002 through a phase 1 trial. Exelixis had originally licensed XB002 from Iconic Therapeutics in 2020, based on preclinical data that suggested the ADC had "best-in-class potential" for treating solid tumors.

In summary, while Exelixis is discontinuing the development of XB002, the company remains focused on other promising areas within its pipeline, particularly zanzalintinib and Cabometyx, to drive future growth and address unmet medical needs.