Two companies that have been the subject of recent licensing deals are taking projects into their first-in-human studies. The projects involved are Kumquat’s KRAS inhibitor KQB368, and Context Therapeutics’ anti-Nectin-4 T-cell engager CT-202, as revealed in new listings on the clinicaltrials.gov registry.
Only the latter was the subject of a deal, however, having been licensed from BioAtla in late 2024 for $15m in up-front and near-term payments – this low fee likely reflecting the proliferation of similarly acting industry assets. Kumquat struck a notable transaction with Bayer last year, but that concerned a separate pipeline asset.
The Kumquat project now advancing into phase 1 is a KRAS inhibitor coded KQB368, which appears to be a variation on KQB365, a separate molecule that was already in human studies. Both projects are being tested in KRAS G12C or G12D mutant solid tumours, suggesting that they have especially notable activity against these KRAS variants.
Meanwhile, the Bayer deal, worth $1.3bn in biodollars (the up front wasn’t disclosed) concerned KQB548, a KRAS G12D inhibitor. KQB548 is now coded BAY 3771249, and is in two phase 1 trials. Kumquat has separate tie-ups with Takeda and Lilly.
For its part, Context has to contend with CT-202 being one of 53 active industry projects acting on Nectin-4, according to OncologyPipeline, most being, like Pfizer’s marketed Padcev, ADCs. Only five use a CD3-anchoring T-cell engager modality, however, and among these CT-202 appears to be the first to have entered the clinic.
Recently disclosed first-in-human studies*
Several other first-in-human trial entrants are also noteworthy. One is BHB810, an anti-CDH17 ADC in development by the private US biotech BigHat Biosciences; CDH17 has emerged as an extremely popular target for ADCs, and BHB810 appears to be BigHat’s first clinical-stage asset.
A rather more novel target, kappa myeloma antigen (KMA), is being pursued by a Car-T therapy in development at HaemaLogiX. No other companies appear to be pursuing KMA blockade, though HaemaLogiX has separately worked on naked antibody and T-cell engager approaches against it, in addition to Car-T.
A more curious move is Kivu’s decision to pursue CEACAM5 blockade with the ADC KIVU-305. This target has seen numerous disappointments, including two at Sanofi: the French company first discontinued tusamitamab ravtansine, which failed in a pivotal lung cancer study, and then saw its second attempt, tusamitamab sonditecan, go on clinical hold in several EU countries.
Meanwhile, Shanghai Henlius/Palleon are pursuing the B7-H3 target with HLX316. That’s nothing new – B7-H3 is another popular tumour antigen for ADC development – but HLX316 uses a novel design, combining targeting domains with a sialidase; the aim is additionally to remove sialic acid from tumour cells, something that’s hoped to enhance immune response.
