Akeso, Inc. (9926.HK) ("Akeso" or the "Company")  announced that the first patient has been dosed in a Phase II clinical study (AK146D1-202) evaluating AK146D1, the Company's internally developed TROP2/Nectin-4 bispecific antibody-drug conjugate (bsADC), in combination with ivonescimab (the Company's PD-1/VEGF bispecific antibody), for the treatment of advanced breast cancer.

This study aims to explore the potential of Akeso's "IO2.0 + ADC2.0" regimen in advanced breast cancer, with a particular focus on first-line treatment of HR+/HER2- breast cancer and triple-negative breast cancer (TNBC).

Breast cancer is the second most common malignancy worldwide, with approximately 2.3 million new cases diagnosed annually. Advances in molecular subtype-guided precision medicine—including targeted therapies, immunotherapies, and ADCs—have improved outcomes for patients with certain subtypes. Nevertheless, substantial opportunities remain to enhance both efficacy and safety. Persistent challenges such as resistance in later-line settings, limited availability of effective agents, and marked tumor heterogeneity continue to create significant and urgent unmet clinical needs. These include the limited efficacy of immuno-oncology approaches in PD-L1-negative patients and in those who develop resistance to anti-PD-1 therapy, as well as the safety constraints of ADCs that restrict both therapeutic benefit and the number of treatment lines that can be administered. Exploring novel targets, optimizing combination strategies, and identifying predictive biomarkers for efficacy and resistance remain critical priorities in breast cancer research.

Ivonescimab, a first-in-class PD-1/VEGF bispecific antibody, has shown strong clinical results compared to PD-1 inhibitor-based therapies across multiple Phase III studies. AK146D1 is a next-generation ADC candidate that has demonstrated potent antitumor activity and a favorable safety profile in early clinical studies. The combination of AK146D1 and ivonescimab has the potential to improve clinical efficacy while maintaining a manageable safety profile, potentially expanding treatment options for patients with advanced breast cancer.

Guided by its IO2.0 + ADC2.0 strategy, Akeso is driving the continuous evolution of treatment paradigms for major malignancies such as non-small cell lung cancer and breast cancer.

In the immuno-oncology field, Akeso has two approved bispecific antibodies for cancer treatment. The Company is actively evaluating ivonescimab and cadonilimab in combination with its proprietary next-generation ADC candidates. Increasingly, global partners recognize both ivonescimab and cadonilimab as preferred agents for combination regimens and breakthrough therapy explorations across a wide spectrum of tumor types.

In the ADC space, Akeso has built a differentiated pipeline of next-generation candidates, including AK146D1, AK138D1, AK157D1, and AK158D1 (a bispecific ADC), which are currently in clinical development. These agents are designed to address the narrow therapeutic window and safety limitations commonly associated with first-generation ADCs.

Building on the encouraging Phase II clinical data of ivonescimab in breast cancer, a Phase III study evaluating an ivonescimab-based combination as first-line treatment for TNBC is currently underway. In addition to AK146D1, Akeso is also conducting a Phase Ib/II study of its next-generation HER3 ADC (AK138D1) in combination with ivonescimab.

Akeso's IO2.0 + ADC2.0 strategy utilizes multi-target and multi-mechanism combinations to harness the synergistic advantages of its pipeline assets. The Company is building a broad portfolio of combination therapies across multiple subtypes and treatment lines in major cancers. This approach seeks to improve clinical outcomes, address resistance challenges, and provide more effective treatment options for patients with advanced breast cancer.

Looking ahead, Akeso continues to advance additional IO2.0 + ADC2.0 combination therapies across a growing range of high incidence tumor indications.