AACR 2026 – conjugates remain centre stage

If last year’s AACR illustrated an explosion in the development of antibody-drug conjugates with dual payloads, this year’s instalment suggests that such efforts aren’t about to slow down. Presentation titles, released this week, identify 17 industry projects to be featured in the meeting’s poster sessions.

Some of these are previously unknown projects, while for some others that were in the public domain targets are being revealed for the first time; others still are only now being described as carrying more than one payload. Perhaps the most remarkable is an ADC that uses not just two but three payloads: Araris’s ARC-401.

The theory is that patients can develop resistance not just to an ADC’s antigen target but also to its payload, so the idea is that a conjugate with more than one payload can circumvent such resistance. And presumably a molecule with three rather than two payloads might do this even better, though design considerations have to be thought through carefully.

$400m takeover

As of last year Araris operates as a subsidiary of Taiho (itself a division of Otsuka), having started as a spin-out of the Paul Scherrer Institute. It developed an ADC linker technology that’s also attracted a deal with Roche’s Chugai division, and it originally acquired the anti-Nectin-4 MAb used in ARC-401 from ARS Pharmaceutical.

Despite Araris’s preclinical development status Otsuka valued the business at $400m up front, a sum that represents a massive bet on multiple-payload ADCs. An IND is expected to be filed for ARC-401 this year.

Among other AACR posters DualityBio is revealed to be working on a dual-payload ADC targeting tumour-associated MUC1 (TA-MUC1). So far this has mostly been the domain of Daiichi Sankyo with sacomitatug deruxtecan, an ADC using an analogue of a MAb licensed from Glycotope.

And Sutro’s second dual-payload ADC is revealed to target HER2, though it apparently has yet to be named. That company started work here last year after discontinuing its former lead, luveltamab tazevibulin, but until now its only disclosed dual-payload ADC was STRO-227, targeting PTK7.

AACR posters on ADCs with multiple payloads (all preclinical)

Note: *triple payload; the rest carry dual payloads.

PTK7 is separately the target of Zymeworks’ ZW418, which hits two distinct epitopes of this protein. That preclinical project uses a traditional single payload, but it’s the fact that this payload is a pan-RAS inhibitor that makes ZW418 unique; presumably its AACR poster will explain the biology backing such an unusual approach.

Single-payload ADCs will also feature at AACR’s plenary sessions, with two presentations profiling clinical data from assets that have recently entered pivotal development: GSK/Hansoh’s risvutatug rezetecan and CSPC’s SYS6010. 

And Ipsen’s IPN60300 is revealed as targeting integrin α2; the only other industry asset with this target, according to OncologyPipeline, was Eisai’s now discontinued small-molecule inhibitor E7820.

Selected AACR presentations involving ADCs

AACR 2026 takes place in San Francisco on 17-22 April.