When two antigens are better than one

Among recent cell therapies starting human testing Essen Biotech's BAH2573 stands out for combining activity against BCMA as well as against GPRC5D. These multiple myeloma antigens feature a vast crowd of industry projects, and activity has picked up among companies trying to target both, across several different modalities.

Perhaps the biggest splash here has been made by Johnson & Johnson with JNJ-79635322, though this molecule is a trispecific T-cell engager. A separate bispecific Car-T therapy also features among first-in-human trial starts, and this targets CD38 and CLL-1; meanwhile, the more traditional antibody approach sees two new bispecifics, from Bao Pharma and 3SBio.

J&J's JNJ-79635322 made an impression with early data at the recent ASCO conference. One question for that group is the extent to which this project could cannibalise sales of Tecvayli and Talvey, which target BCMA and GPRC5D respectively, and how it might fit into a complex paradigm that also includes J&J's Legend-partnered anti-BCMA Car Carvykti.

A similar consideration, though at a much earlier stage of development, might apply to the private biotech Essen, which in multiple myeloma claims already to have BAH245, a Car-T therapy against BCMA and CD19, in phase 2. Now this has been joined by a phase 1 study of the anti-BCMA x GPRC5D Car-T project BAH2573.

The latter is said to target multiple myeloma cells displaying either antigen, or both together, and while the study precludes prior Car-T treatment it appears that patients earlier given anti-BCMA or GPRCD therapy in a different modality might be allowed. The Chinese study actually began in April, but has only now been disclosed in a clinicaltrials.gov entry.

AML

The other bispecific Car newly into the clinic is Shanghai Unicar-Therapy's U32, which judging by exclusion criteria likely hits CD38 and CLL-1. Though the former is normally associated with multiple myeloma it's also found on some leukaemic cells, and U32's first-in-human trial concerns acute myelogenous leukaemia, with the precondition that this must be positive for expression of CD38 or CLL-1.

OncologyPipeline reveals numerous competing AML Car-T therapies that target CLL-1, including several bispecific approaches, typically combining this with activity at CD33.

Other new clinicaltrials.gov listings include Cell & Gene Biotech's CG-102-12C, which hits the increasingly popular liver cancer target GPC3, and Outpace Bio's OPB-101. The latter targets mesothelin, a strategy that's not delivered many successes. Cell & Gene separately also has an anti-BCMA Car in clinical trials.

New cell therapy entrants also feature the private Swiss biotech Onward Therapeutics, whose majority-owned Emercell subsidiary has gone into the clinic with OT-C001, an allogeneic NK cell therapy, in combination with Rituxan. OT-C001 cells are unmodified, but are said to be "highly activated and alloreactive".

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 22 Jun & 3 Jul 2025.

In bispecific MAbs, Bao Pharma is advancing KJ015, a biparatopic molecule against HER2. Bao says that, thanks to its ability to maintain high affinity for two HER2 epitopes simultaneously, KJ015 clusters with the antigen on the cell membrane; its lead indication is gastroesophageal adenocarcinoma.

Meanwhile, 3SBio's SPGL008 combines B7-H3 blockade with activity on the inflammatory cytokine IL-15. 3SBio has gained fame as the originator of the anti-PD-1 x VEGF MAb SSGJ-707, licensed by Pfizer for $1.25bn; it recently went into the clinic with the bispecific MAbs SSGJ-708 (PD-1 x TGF-β) and SSGJ-709 (PD-1 x Lag3).