What now for NK-cell engagers?

News that the insolvency of Affimed has swiftly been followed by the sidelining of yet another of Innate Pharma's NK-cell engagers has prompted a burning question: how many other companies are, like these two, still pursuing the NK-cell engager approach, and what do the latest setbacks suggest about their prospects?

A search of OncologyPipeline reveals nearly 20 individual molecules that apparently remain in active development, eight of which are in clinical trials run by groups including AbbVie, Merck & Co and BeOne. However, optimism will be tempered by the revelation that Bristol Myers Squibb quietly canned its deal with Dragonfly, and by the threat of a cash crunch at GT Biopharma.

The case of Dragonfly is especially intriguing. This company succeeded in generating the most notable big pharma buy-in for its so-called "trinket" (trispecific NK-cell engager therapy) approach, in deals with Celgene/Bristol Myers Squibb, Merck & Co and AbbVie, each of which was subsequently expanded, and Gilead.

Dragonfly doesn't fly

However, it recently emerged that the most advanced Dragonfly/Bristol asset, an anti-CD33 molecule coded CC-96191, had its phase 1 AML study terminated in May, with "business objectives have changed" given as the reason on clinicaltrials.gov. 

Now Bristol has confirmed to ApexOnco that the entire deal had been scrapped. The tie-up was actually terminated last October, a spokesperson said, but the fact doesn't ever appear to have been announced publicly. Earlier Bristol handed back to Dragonfly an IL-12 project it had licensed in a separate deal.

And things have also gone quiet on what might be Dragonfly's biggest deal to date, a 2022 tie-up with Gilead over DF7001 worth $300m up front. An IND was to have been filed for DF7001, a 5T4-targeting NK-cell engager, in 2023, but nothing has been announced about this asset since.

Indeed, the last public statement on Dragonfly's website dates from November 2024. According to clinicaltrials.gov, however, studies of Dragonfly's anti-HER2 and EGFR projects continue, as do those for the Merck-partnered MK-4464 and the AbbVie-partnered ABBV-303. 

The other significant player in NK-cell engagers is BeOne, which put the MUC1-targeting BGB-B3227 into human trials a year ago.

NK-cell engager projects in development

Source: OncologyPipeline.

Meanwhile, it was arguably the 2021 discontinuation of Roche's deal with Affimed over an anti-BCMA NK-cell engager that was a portent of future troubles for that biotech. Though Affimed's wholly owned anti-CD30 project acimtamig had some promise, the company found it impossible to raise additional cash for it, and filed for insolvency in May.

It might be that remaining investors in GT Biopharma, another NK-cell engager player, are eyeing such developments nervously. GT's valuation has collapsed to just $2.8m, and the company reported $5.3m of mid-2025 cash, enough to get it only into the first quarter of 2026.

NK-cell engagement is achieved by targeting either CD16 or its subgroup variant CD16A, as an "anchor" to NK cells in the same way that CD3 is used in T-cell engager therapeutics. GT is notable for having originated projects that hit the target antigen plus CD16, as well as including an IL-15 moiety to boost proliferation.

There have been other takes on multispecific approaches, not least from Dragonfly – which adds the activating receptor NKG2D as a target – and Innate, which additionally hits the triggering receptor NKp46. However, Sanofi's gradual backing away from Innate, and the uncertainty around Dragonfly, do little to allay fears that time for this modality is fast running out.

Other NK-cell engager work

Source: OncologyPipeline.