Xencor pulls back from Genentech cancer pact to cut costs as CytomX drops ex-AbbVie ADC

Xencor and CytomX Therapeutics have taken a scalpel to their pipelines, stopping work on an ex-AbbVie antibody-drug conjugate (ADC) and pulling back from a co-development deal with Genentech to focus cash on other projects.

Compared to CytomX, Xencor is making more substantial changes to its strategy. Seeking to extend its runway into 2027, Xencor is rethinking its plans for three programs, including the IL-15 collaboration it entered into with Roche's Genentech unit in 2019. Since forming the deal, Xencor has funded 45% of the worldwide development costs of XmAb306 and other IL-15 assets. Now, the biotech is opting out of cost sharing.

Genentech has moved the potency-reduced IL15/IL15Rα-Fc fusion protein XmAb306 into a set of phase 1 trials in various cancers in combination with drugs including its checkpoint inhibitor Tecentriq. Xencor has previously warned investors that its support for the program, which would have secured it a 45% share of net profits from sales, may require it “to incur substantial costs in excess of available resources.”

Xencor disclosed the change to the IL-15 collaboration alongside updates on its plans for vudalimab and XmAb104. Citing the “rapidly changing competitive environment,” the biotech revealed it is stopping the gynecologic tumor cohorts in the monotherapy study of its PD-1xCTLA-4 bispecific vudalimab. Work on other indications is continuing. 

The XmAb104 program is stopping altogether. Xencor decided to halt internal development on XmAb104 after data from phase 1 expansion cohorts fell short of the efficacy criteria for progressing further. The study expansion enrolled patients with microsatellite stable colorectal cancer. 

Xencor shared details of its updated strategy minutes before CytomX provided an update on CX-2029, a CD71-directed ADC. AbbVie walked away from CX-2029 in March, terminating the pact after getting a look at results from a phase 2 trial. 

CytomX reacquired the full rights to the program and began evaluating the next steps. Late Tuesday, the biotech revealed there will be no progress anytime soon, stating that “based on current priorities, [it] will not be directing significant additional investment in this program in the near-term.” The biotech made the call despite telling investors that it is “encouraged by the anti-tumor activity.”

Another company making program cuts is Genmab, which has axed an antibody-based therapy called GEN3009, according to a third quarter earnings report issued Tuesday. The bispecific was created using the company's DuoHexaBody technology targeting CD37.

Genmab had been testing GEN3009 in a phase 1/2 trial for B-cell non-Hodgkin lymphomas. That trial has now been discontinued based on a strategic review of Genmab's portfolio rather than safety or regulatory concerns, the company noted.

Editor's Note: This story was updated at 9:08 a.m. ET on November 8, 2023, to add details about Genmab's program discontinuation.