Akeso has received clinical trial clearance from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for its investigational next-generation B7-H3-targeting antibody-drug conjugate (ADC), AK157D1.

The clearance allows Akeso to initiate a Phase I clinical trial evaluating AK157D1 in patients with advanced malignant solid tumours. The company also plans to investigate the candidate in combination with its proprietary bispecific antibodies ivonescimab and cadonilimab.

AK157D1 is the third next-generation ADC candidate from Akeso to enter clinical development, following AK146D1, a TROP2/Nectin-4-targeting ADC, and AK138D1, a HER3-targeting ADC. The latest regulatory clearance further advances the company’s IO2.0 + ADC2.0 strategy, which combines next-generation immuno-oncology approaches with advanced ADC technologies.

B7-H3 is highly expressed across a wide range of solid tumours, including non-small cell lung cancer, small cell lung cancer, prostate cancer, oesophageal cancer, nasopharyngeal carcinoma, colorectal cancer, breast cancer and glioblastoma. Its relatively limited expression in normal tissues makes it a potential broad-spectrum target for cancer therapy.

AK157D1 was developed entirely in-house using Akeso's proprietary technology. The ADC comprises a recombinant humanised IgG1 monoclonal antibody designed to target B7-H3 and is site-specifically conjugated to DXd, a camptothecin-derived topoisomerase I inhibitor, through an MC-AAA linker attached to interchain cysteine residues.

In preclinical studies, AK157D1 demonstrated potent antitumour activity alongside a favourable safety profile. Akeso said these characteristics could potentially help address some limitations associated with existing ADCs, including haematologic toxicity and interstitial lung disease, while supporting further evaluation of the candidate as both a monotherapy and combination treatment.

The clinical clearance adds another candidate to Akeso's growing next-generation ADC pipeline. The company is developing its IO2.0 + ADC2.0 strategy around proprietary bispecific and multispecific antibody technologies, with ivonescimab and cadonilimab serving as key immuno-oncology assets.

Akeso is evaluating combinations of these bispecific antibodies with its proprietary ADC candidates, with the aim of developing new treatment approaches across multiple tumour types.

The company currently has two approved bispecific antibodies for cancer treatment and is advancing additional next-generation ADC programmes. AK146D1 and AK138D1 have already entered clinical development, while AK158D1, a bispecific ADC, is also expected to enter clinical development.