After nearly 10 years leading Xencor’s clinical development, Chief Medical Officer, Paul Foster, M.D., is calling it quits. The biopharma veteran is set to retire in October, capping a 35-year career in academia, medical practice and industry.
The announcement comes as the antibody specialist moves two more programs into the clinic and works to resume a phase 1 study of its Novartis-partnered blood cancer drug.
Xencor didn’t have the best start to 2019, with Novartis handing back the rights to a bispecific antibody it licensed in a 2016 deal worth $150 million up front. One month later, a second asset from the deal—which came with a promise of up to $2.41 billion in milestones—ran into a clinical hold from the FDA due to a pair of patient deaths that were “at least possibly” treatment-related.
That program, XmAb14045, was in a phase 1 study in patients with relapsed or refractory acute myeloid leukemia and other blood cancers expressing CD123. The bispecific targets CD3 and CD123. The FDA placed the hold after Xencor submitted safety reports about two patient deaths—one patient had cytokine release syndrome (CRS) after the first dose of XmAb14045, while the other developed acute pulmonary edema after several doses.
After working with Xencor to change the study protocol, the FDA lifted the partial clinical hold on April 30. The company is now working to resume enrollment for that study.
Although Xencor lost Novartis as a partner on one of its programs, it picked up a new partner, licensing its preclinical-stage IL-15 cytokine therapeutics to Genentech for $120 million up front in February.
Since then, Xencor has inked an R&D deal with Astellas and started phase 1 studies for two more bispecific antibodies in advanced solid tumors: XmAb2314, which targets PD-1 and ICOS and XmAb22841, which targets CTLA-4 and LAG-3. The latter treatment is being tested in combination with Keytruda in an effort to block three checkpoints at once.
Xencor’s most advanced program, XmAb5871 hit a snag last October, when it missed its primary endpoint in a phase 2 study testing it in lupus. Though the treatment beat placebo at improving disease, it didn’t do so with enough of a margin to be declared a success. However, the company considered the data as a “positive trend” that still contained a “promising treatment effect” worthy of future study. It plans to move forward with a phase 3 study of XmAb5871 in a different indication, IgG4-related disease, a chronic inflammatory disorder, but hasn’t written off lupus or SLE just yet.
“[We] are exploring further development in SLE in the context of partnering,” said CEO Bassil Dahiyat at the time.