Akeso, Inc. (HKEX: 9926) today announced that the first patient has been enrolled in the Phase Ib/II clinical study (AK138D1-202) evaluating its internally developed next-generation HER3 antibody-drug conjugate (ADC), AK138D1, as either monotherapy or in combination with ivonescimab for the treatment of advanced breast cancer.

HER3 is broadly expressed across various solid tumors, including breast, ovarian, colon, gastric, lung, skin, and pancreatic cancers, affecting millions of patients globally. While traditional HER3-targeted ADCs have demonstrated therapeutic potential in combination settings, their clinical utility has historically been constrained by dose-limiting toxicities.

AK138D1 is a next-generation, differentiated HER3-targeting ADC developed in-house by Akeso. Leveraging a unique, innovative design, AK138D1 is engineered to reduce uptake in normal tissues, thereby minimizing off-target toxicities and widening the therapeutic window. Furthermore, its design prevents the clustering of ADC molecules on the tumor surface, enhancing deep tissue penetration and uniform distribution to overcome the "binding site barrier". Early-stage clinical studies conducted in China and Australia have demonstrated that AK138D1 exhibits robust anti-tumor activity in solid tumors and breast cancer, coupled with an excellent safety profile, notably characterized by low hematologic toxicity and the absence of interstitial lung disease (ILD). This compelling balance of efficacy and safety overcomes common limitations of conventional ADCs, establishing a foundation for AK138D1 to be explored in diverse combination therapeutic regimens.

The AK138D1-202 study focuses on the two major breast cancer subtypes with the greatest unmet need: hormone receptor-positive, HER2-negative (HR+/HER2-) disease, which accounts for approximately 65% of all breast cancers, and triple-negative breast cancer (TNBC), which represents 10-20% of cases. The trial enrolls patients across multiple treatment lines from treatment-naïve to heavily pretreated, and includes diverse PD-L1 expression levels. Breast cancer remains the most common cancer among women worldwide, with an estimated 2.3 million new cases diagnosed annually. Substantial unmet needs persist in both first-line and later-line settings for HR+/HER2- breast cancer and TNBC.

Early data from AK138D1 studies have already shown meaningful efficacy and a strong safety profile in breast cancer. Concurrently, a Phase III study of ivonescimab-based combination therapy in first-line TNBC is ongoing. The combination of AK138D1 and ivonescimab is poised to emerge as a highly differentiated "IO2.0 + ADC2.0" therapeutic strategy for advanced breast cancer.

As IO+ADC combinations become a cornerstone of global oncology research, Akeso is strategically and efficiently building a comprehensive global portfolio of these next-generation therapies, leveraging its proprietary leadership in bispecific and multispecific antibody platforms.

On the IO front, Akeso stands as the only company globally with two approved bispecific antibodies for oncology, spearheading the advancement of IO2.0 therapies. Regarding its ADC pipeline, Akeso's development of AK146D1 (a Trop2/Nectin4 bispecific ADC) and AK138D1, among other innovations, aims to resolve the toxicity-related limitations of current ADCs and propel the field into the "ADC2.0" era.