Innovent takes the dual payload glory

The hot area of dual-payload antibody-drug conjugates, which only entered the limelight last year, suddenly has not one but two clinical-stage assets. Innovent's IBI3020, which targets CEACAM5 and comprises two undisclosed payloads, has just begun a first-in-human solid tumour study.

Innovent promised in March that INI3020 would start phase 1 this year, and the study has just emerged among new listings on clinicaltrials.gov, which also reveal an ADC against the unusual target TAG-72, and another attempt at diversification from Exelixis. For Innovent the dual-payload ADC push puts the company just ahead of China's Chengdu Kanghong.

It was Chengdu Kanghong's TROP2-targeting KH815 that looked like becoming the first ever dual-payload ADC into the clinic when its study went up on clinicaltrials.gov in March, with a planned 30 April start date. However, that study has yet to begin recruiting patients, according to the registry.

According to clinicaltrials.gov the study of Innovent's IBI3020 began just a day earlier, on 29 April, and is now recruiting patients. Little is known about each molecule, and without more details about their respective characteristics it's hard to gauge their potential; design is thought not to be as simple as just attaching to a MAb two payloads instead of one.

Another player in the dual-payload ADC space is Callio, with assets that group picked up from Hummingbird Bioscience. Separately, in October 2023 and well before this deal was struck, Hummingbird licensed its anti-HER3 (single-payload) ADC HMBD-501 to Endeavor BioMedicines.

It's only now that HMBD-501, now coded ENV-501, is starting a phase 1 trial, in HER3-positive solid tumours. Possibly access to more funds was a gating factor for going into the clinic, and notably Endeavor closed a $133m series C venture capital round just last month.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 20 Apr and 8 May 2025.

While many ADC companies seem to be chasing ever-popular targets including EGFR, B7-H3 and TROP2, one that stands out is the private US biotech Tagworks, whose lead project, TGW101, hits TAG-72.

A preclinical poster at AACR revealed TGW101 to be no ordinary ADC; its MMAE payload isn't released intracellularly in a random fashion, but features "controlled release in the tumour microenvironment" only once a so-called small-molecule trigger molecule, coded TRG001, is added. This approach is now being put to the test in a just-begun phase 1 study.

OncologyPipeline reveals no other anti-TAG-72 ADCs in development, though there are a few Car-T and Car-NK therapies against this target. Even more unique is the area of bispecific MAbs that hit NKG2A as well as PD-L1, whose only exponent is Exelixis's XB628 – another molecule new to human trials this month.

XB628 also featured in a preclinical AACR poster, which disclosed its design and said its goal was to inhibit both adaptive and innate immune checkpoints, given the presence of NKG2A on NK and some CD8+ T cells. The rationale for its development was said to be a phase 1/2 study combining AstraZeneca's Imfinzi with Innate Pharma's anti-NKG2A MAb monalizumab.

XB628, along with the USP1 inhibitor XL309, the anti-5T4 ACD XB010, the tissue factor-targeting ADC XB371 and the kinase inhibitor zanzalintinib, represents Exelixis's efforts to diversify away from the workhorse blockbuster Cabometyx.