VEGF bispecifics enter the conjugate era

With biopharma’s push into anti-PD-(L)1 x VEGF bispecifics showing no sign of a slowdown, it was only a matter of time before someone tackled this mechanism with an antibody-drug conjugate. Step forward Alphamab, whose JSKN027 is to enter its first clinical study next month, a new listing on clinicaltrials.gov has revealed.

The company first disclosed that it was working on this molecule last year, and announced that an IND had been accepted by China’s regulator last December. It argues that JSKN027 is the first anti-PD-(L)1 x VEGF to use an ADC modality, and perhaps this feature will allow the molecule to stand out in a field where no fewer than five naked MAbs are in pivotal trials for lung cancer alone.

On a structural basis JSKN027 is similar to BioNTech/Bristol Myers Squibb’s pumitamig in that it hits not PD-1 but PD-L1, something that might help anchor it to tumour cells as well as to block PD-1/PD-L1 interaction. And its other target is VEGFR2, similar to Ottimo’s jankistomig; it’s been suggested that selectivity for VEGFR2 can minimise VEGF-related side effects.

However, the most salient feature of Alphamab’s molecule is that it’s an ADC. An early scientific publication revealed that JSKN027 used a topoisomerase 1 inhibitor payload, conjugated to the MAb’s Fc region at an average antibody-to-drug ratio of 4, and a cleavable linker.

Alphamab has argued that JSKN027 has multiple mechanisms of action, claiming targeted and bystander ADC activity, as well as inhibiting tumour angiogenesis by blocking VEGF/VEGFR2 signalling. Now the group will try to show in a clinical trial that such an approach might be better than using a more typical antibody or fusion protein.

Recently disclosed first-in-human studies*

Note: *these projects were first listed on the clinicaltrials.gov database between 6 and 11 Feb 2026.

Recent new listings on the clinicaltrials.gov registry also include another ADC, Hutchmed’s HMPL-A580. The molecule is the second one derived from Hutchmed’s antibody-targeted therapy conjugate platform, meaning that it uses a very unusual payload: a PI3K/PIKK inhibitor.

As for HMPL-A580’s target, this hasn't formally been disclosed. However, the molecule's listing on the Chinese clinical trial registry lists EGFR-mutated NSCLC among inclusion criteria, and says tumour samples must be available for EGFR expression testing, so it's likely that HMPL-A580 is an anti-EGFR ADC.

And followers of the relentless march of in vivo Car-T therapy, a field that Lilly entered this month through the acquisition of the private company Orna Therapeutics, will note the quiet progress Legend Biotech has been making here. The latest Legend in vivo Car-T asset to enter human trials is a project coded LVIVO-TaVec400. 

The target of LVIVO-TaVec400 hasn’t been disclosed, but the therapy is being studied in multiple myeloma. This means that Legend now has three clinical-stage in vivo Car-T assets, after LVIVO-TaVec200 (targeting GPRC5D) and LVIVO-TaVec100 (CD19 x CD20) entered human trial in recent months.