Boehringer Ingelheim has joined the surge of companies entering the B-cell depletion space. But while its peers have largely focused on CAR-Ts and bispecifics, the German drugmaker has paid Cue Biopharma $12 million for a novel preclinical program that could eliminate some of the risks of rival approaches.
Clinical data on a CD19-directed CAR-T cell therapy in lupus has sent interest in the depletion of B cells to treat autoimmune and inflammatory diseases into overdrive in recent years. Companies with experience of using cell therapies and bispecifics to take out cancer cells have quickly added autoimmune programs to their pipelines and the likes of Merck & Co. and Sanofi have bought their way into the space.
Boehringer disclosed its move after the market closed Monday. The company is paying $12 million and committing up to $345 million in milestones for global rights to B-cell depletion compounds including CUE-501.
Cue applied technology it initially tested in the treatment of cancers to the development of CUE-501. The idea is to make B cells appear as if they are infected with a virus such as cytomegalovirus or SARS-CoV-2. Most people have been exposed to those viruses and, as such, have long-lived memory cytotoxic T cells that will recognize cells infected with the pathogens and launch immune attacks.
The approach could enable Cue to hijack the body’s immune system to deplete B cells. Bispecifics offer another way to turn the immune system against B cells but Cue has identified their reliance on CD3 as a potential weakness. As CEO Daniel Passeri explained at a Piper Sandler investor event in December 2024, CD3 will activate every T cell that it comes into contact with.
“The side effect of that is you'll end up with cytokine storm. Those patients are going to have to be monitored. You typically have to have slow infusion,” Passeri said. “What we're looking at is the ability to paint any particular cell, in this case B cells, with a viral epitope. The safety profile should be much, much better. In fact, we don't see any cytokine release when we have looked at these molecules.”
Boehringer will conduct collaborative research on CUE-501 for up to four years. The agreement allows the drugmaker to elect additional or alternative compounds targeted at B cell depletion. Boehringer has a license to commercialize the compounds and is responsible for all further development. Cue cannot develop any molecule for applications in B-cell depletion during the research term of the deal.
Passeri said Cue was in late-stage partnering discussions with a number of parties as of December. The selection of Boehringer gives Cue a $12 million cash infusion, which the biotech immediately added to by pricing a $20 million public offering. Cue ended last year with $22.5 million, an amount it predicted would meet its obligations into the fourth quarter of 2025.