Roche has given two early-phase bispecifics the heave-ho, ending work on a HER2xCD3 prospect and an IL-15 candidate it picked up from Xencor.
The drugmaker removed (PDF) the molecules from its phase 1 pipeline as part of its fourth-quarter clearout. The HER2 asset, known as both RG6194 and runimotamab, was in development in breast cancer. Vir Biotechnology recently reported phase 1 data on its rival HER2 bispecific VIR-5818.
The IL-15 candidate, efbalropendekin alfa, was designed to drive the expansion and activation of T cells and natural killer cells by fusing IL-15 to its alpha receptor and Xencor’s bispecific Fc domain. Xencor revised the terms of the deal with Roche’s Genentech late in 2023, opting out of a deal to split costs and agreeing to success-related fees that could have totaled $600 million.
Roche also included RG7827, a 4-1BBxFAP bispecific antibody, on the list of the candidates removed from its phase 1 pipeline. However, a Roche spokesperson clarified that the action relates to the company’s decision to end work on the CEAxCD3 bispecific candidate cibisatamab.
“Following the discontinuation of cibisatamab, the phase 1 dose escalation study evaluating the combination of cibisatamab with FAP-4-1BBL is discontinued. This decision does not affect any potential future research and development of FAP-4-1BBL beyond the combination with cibisatamab,” the Roche spokesperson said.
Roche stopped studying cibisatamab in combination with its checkpoint inhibitor Tecentriq in colorectal cancer patients last year but continued to test the asset with its 4-1BBxFAP bispecific. At the time, Teresa Graham, CEO of Roche Pharmaceuticals, said “we've seen encouraging early data that would lead us to believe that further study is necessary or warranted.”
Roche has pursued a multifront attack on FAP, studying CD40 and DR5 bispecifics, respectively RG6189 and RG7386, and the immunocytokine RG7461, but dropped those assets over time. The 4-1BB bispecific RG7827, also known as RO7122290, recently completed phase 1/2 trials in urothelial and colorectal cancers.
Amgen returned a 4-1BBxFAP bispecific to Molecular Partners almost three years ago, but FAP remains a target of interest for multiple companies. Molecular Partners is still developing the FAPxCD40 bispecific MP0317, Novartis is working (PDF) on radioligand therapies, Genmab has a FAPxDR4 candidate in phase 1 and Avacta Therapeutics is expanding development of its peptide-drug conjugate.
Roche also reported the removal of a pair of phase 1 candidates managed by its Chugai subsidiary. One of the assets was a glypican-3xCD3 T cell-redirecting antibody for treatment of solid tumors. The other axed Chugai candidate was SPYK04, a RAF-MEK molecular glue that the Japanese drugmaker removed (PDF) from its pipeline in October.