Roche Reshapes Early-Phase Pipeline, Drops Multiple Bispecific Candidates

Swiss pharmaceutical giant Roche has announced significant changes to its early-phase pipeline, discontinuing several bispecific antibodies and immunotherapy candidates. The move reflects the company's ongoing efforts to optimize its research and development portfolio in a competitive oncology landscape.

HER2 and IL-15 Bispecifics Discontinued

Roche has removed two early-phase bispecific candidates from its pipeline. The first, RG6194 (runimotamab), was a HER2xCD3 bispecific antibody being developed for breast cancer. This decision comes as competitors like Vir Biotechnology continue to advance their own HER2-targeted bispecifics, with Vir recently reporting phase 1 data on VIR-5818.

The second discontinued candidate is efbalropendekin alfa, an IL-15-based immunocytokine developed in partnership with Xencor. This molecule was designed to stimulate T cells and natural killer cells by fusing IL-15 to its alpha receptor and incorporating Xencor's bispecific Fc domain. The termination of this program follows a recent revision of the collaboration agreement between Xencor and Roche's Genentech unit, where Xencor opted out of cost-sharing in exchange for potential success-based fees.

FAP-Targeted Programs and Solid Tumor Bispecifics

Roche has also made adjustments to its fibroblast activation protein (FAP)-targeted pipeline. The company clarified that while RG7827, a 4-1BBxFAP bispecific antibody, was initially listed among discontinued programs, this was an error. Instead, Roche has ended development of cibisatamab, a CEAxCD3 bispecific antibody.

The discontinuation of cibisatamab has led to the termination of a phase 1 dose escalation study evaluating its combination with FAP-4-1BBL. However, Roche emphasized that this decision does not affect potential future development of FAP-4-1BBL in other contexts.

Despite these setbacks, FAP remains a target of interest across the pharmaceutical industry. Companies like Molecular Partners, Novartis, Genmab, and Avacta continue to pursue various FAP-targeted therapies, including bispecifics, radioligand therapies, and peptide-drug conjugates.

Chugai Subsidiary Pipeline Adjustments

Roche's Japanese subsidiary, Chugai Pharmaceutical, has also trimmed its early-phase pipeline. Two phase 1 candidates have been removed: a glypican-3xCD3 T cell-redirecting antibody for solid tumors and SPYK04, a RAF-MEK molecular glue. The latter was previously announced to be discontinued in October 2023.

These pipeline adjustments reflect the dynamic nature of pharmaceutical R&D, where companies must continually reassess their portfolios based on emerging data, competitive landscapes, and strategic priorities. As Roche refines its focus, the industry will be watching closely to see which programs the company chooses to advance and where it may seek to bolster its pipeline through future collaborations or acquisitions.