Akeso has announced the dosing of the first patient in its Phase 1b/2 clinical study (AK138D1-201), evaluating its internally developed next-generation HER3-targeted Antibody-Drug Conjugate (ADC), AK138D1, as a standalone therapy and in combination with ivonescimab for the treatment of advanced Non-Small Cell Lung Cancer (NSCLC).

The study is designed to assess the potential of Akeso's IO2.0 + ADC2.0 therapeutic strategy across multiple treatment settings in advanced NSCLC, including first-line therapy, treatment following EGFR-TKI resistance and treatment after resistance to immuno-chemotherapy.

AK138D1 has been developed to selectively target HER3, a protein closely associated with tumour progression and treatment resistance in NSCLC. Unlike conventional HER3-targeted ADCs, which have been limited by toxicity concerns, AK138D1 has been engineered to minimise uptake in healthy tissues, reduce off-target toxicity and improve tumour penetration. According to the company, early clinical studies conducted in China and Australia demonstrated encouraging anti-tumour activity along with a favourable safety profile, including low haematologic toxicity and no reported cases of Interstitial Lung Disease (ILD).

The combination arm pairs AK138D1 with ivonescimab, Akeso's PD-1/VEGF bispecific antibody, which has demonstrated promising clinical outcomes in multiple Phase 3 studies. The company believes the combination could enhance immune activation while delivering synergistic anti-tumour activity across different NSCLC subtypes, with the potential to maintain a favourable safety profile.

The clinical programme forms part of Akeso's broader IO2.0 plus ADC2.0 strategy, which combines its bispecific antibody expertise with next-generation antibody-drug conjugates to develop new treatment options for cancer patients.

Akeso currently has two approved bispecific antibodies for cancer treatment and is expanding its pipeline through combination studies involving ivonescimab, cadonilimab and proprietary ADC candidates. In addition to AK138D1, the company's ADC portfolio includes AK146D1, which has entered Phase 2 clinical development, while AK157D1 and the bispecific ADC AK158D1 are expected to enter clinical studies.

Multiple Phase 2 studies are currently underway to evaluate combinations of ivonescimab and cadonilimab with AK138D1, AK146D1 and other investigational candidates for solid tumours, including lung and breast cancers.

AK138D1 is an injectable HER3-targeted ADC comprising a fully humanised anti-HER3 IgG1 antibody linked to the topoisomerase I inhibitor DXd through a cleavable linker. Following binding to HER3-expressing tumour cells, the ADC is internalised, releasing DXd to induce DNA damage and trigger tumour cell death. Early studies have indicated potent biological activity and a favourable safety profile, supporting its continued clinical development.

Founded in 2012, Akeso is a biopharmaceutical company focused on the discovery, development and commercialisation of innovative biological medicines. Its research platform spans bispecific and multispecific antibodies, antibody-drug conjugates, T-cell engagers, AI-driven drug discovery, RNA technologies and cell therapies.