MacroGenics faces new competition

MacroGenics, the troubled ADC-focused biotech that recently scrapped its lead asset, vobramitamab duocarmazine, now faces the first clinical competition for the anti-Adam9 ADC MGC028, one of the projects to which it pivoted. Duality Biologics has just put its similarly acting contender DB-1317 into its first phase 1 study, new listings on clinicaltrials.gov reveal.

Also featuring is HengRui's new KRAS G12D inhibitor, HRS-6093, which could find it difficult to rise above the crowd of developers pursuing this and related KRAS approaches. That said, ADC development also remains one of biopharma's favoured strategies, and DB-1317 is one of four new conjugates in the latest batch of initiations.

Adam9, an enzyme thought to play a role in tumourigenesis that is overexpressed in some cancers, is the target of just two active industry projects, according to OncologyPipeline. MacroGenics' MGC028 started phase 1 in March, and now Duality's DB-1317 is going into the clinic, also in a solid tumour trial.

The only other anti-Adam9 ADC is the now discontinued izeltabart tapatansine, which was also originated by MacroGenics, and was licensed to ImmunoGen (now part of AbbVie). The main difference between the two MacroGenics assets is their payload – a tubulin inhibitor for izelta-T versus MGC028's topoisomerase 1 inhibitor; DB-1317 also uses a topo1 inhibitor (pamirtecan), but has a different linker.

More competition

Other ADCs newly into the clinic include InnoCare's ICP-B794, which hits B7-H3; this happens to be the same target as that hit by MacroGenics' ill-fated and now discontinued vobramitamab duocarmazine.

MacroGenics is still active here with a phase 1 asset, vobramitamab tavatecan, but this busy space features far more advanced ADCs from Merck & Co/Daiichi Sankyo (ifinatamab deruxtecan) and GSK/Hansoh (GSK5764227). And Duality itself is active here too, with its BioNTech-partnered BNT324/DB-1311.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 14 and 26 Aug 2025.

There's a little less competition for ADCs aiming to improve on the bispecific EGFR x cMet approach of Johnson & Johnson's approved T-cell engager Rybrevant, with perhaps the most prominent player here being AstraZeneca's tilatamig samrotecan.

The clinical space will shortly include VelaVigo's anti-EGFR x cMet ADC VBC101, which is due to enter phase 1 at the end of September. VelaVigo, another Chinese conjugate specialist, is perhaps best known for originating the anti-Nectin-4 x TROP2 ADC VBC103, to which the private US biotech Avenzo secured opt-in rights last November.

Meanwhile, in small-molecule approaches OncologyPipeline lists 16 clinical-stage KRAS G12D inhibitors, the most advanced of which is Revolution's zoldonrasib. These now include HengRui's HRS-6093, which clinicaltrials.gov discloses starts its first phase 1 study in September.

In addition to all these the competition now includes G12D degraders from Astellas, which has two, Arvinas and Ranok Therapeutics. Still, despite such crowding, business development interest remains, as illustrated by Bayer recently licensing Kumquat Biosciences' KQB548.