Xencor (NASDAQ: XNCR) Chief Executive Bassil Dahiyat said the company is pivoting to become a late-stage clinical developer, using its XmAb platform as the foundation for the transition.
The remarks came Wednesday at the 12th Annual Cantor Fitzgerald Global Healthcare Conference, where executives presented data on several programs spanning oncology and inflammatory diseases.
Dahiyat stated, "This is about Xencor taking the incredibly powerful platform we built, our XmAb platform, and transitioning it and Xencor to being a late-stage development company. This presentation is really the gate for that."
He added that the company would only pursue drugs where it could achieve best-in-class potential.
Chief Strategy Officer Dane Leone characterized the renal cell carcinoma (RCC) landscape as reliant on repeatedly recycling existing classes with diminishing returns and unchanged toxicity profiles.
XmAb819, an ENPP3-targeted T-cell engager in clear cell RCC, has shown an objective response rate of 25% in early blended patient data. The study population is predominantly treatment-refractory, with 60% post-immunotherapy who have received at least two prior tyrosine kinase inhibitors.
The company projects a global total addressable market of approximately $11 billion for XmAb819 in RCC, compared with PD-1 inhibitors generating $5 billion to $6 billion annually, VEGFR TKI drugs producing roughly $5 billion per year, and HIF-2α inhibitors led by Merck's belzutifan now exceeding a $1 billion run rate.
Phase IIb development of XmAb942, a TL1A monotherapy for ulcerative colitis, is on track to hit its primary endpoint—a 12-week modified Mayo score—in the second half of 2025. The program uses a 220-completer design with three dose levels against placebo, and a single dose at the lowest level fully suppressed free TL1A for at least 20 weeks, leveraging a human half-life of 74 days. An interim futility analysis and execution review is expected near year-end.
Xencor also expects first-in-human data from XmAb412, a bispecific IL-23/TL1A molecule described as about half the mass of a typical antibody.
In gynecologic cancers, Phase II data for XmAb541, a Claudin-6 CD3 bispecific, showed a 28% response rate in germ cell tumors and 14% in ovarian cancer. The optimal dose was identified at 60 mg, with higher doses limited by transient hearing loss and cochlear toxicity.
During the quarter, Xencor began a combination study pairing XmAb541 with a B7-H3–targeting CD28 engager referred to internally as the "AND gate." A registration-enabling pivotal study for XmAb819 is targeted to start later this year, with an earlier combination study versus a PD-1 inhibitor expected to open in early 2025. An ESMO update presentation for XmAb819 is scheduled for approximately one month from the conference date.
Partnerships with Astellas and Johnson & Johnson were referenced in connection with ongoing program development.
Xencor reported a current ratio of 6.39, with liquid assets exceeding short-term obligations.
