Akeso, Inc. (9926.HK)  ("Akeso" or the "Company") announced  that it has received clearance from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) to initiate Phase II clinical trials for AK146D1, a first-in-class Trop2 /Nectin4 bispecific antibody-drug conjugate (ADC), and AK138D1, an innovative HER3-targeting ADC.

The studies will evaluate these two novel ADC candidates in combination with the Company's pioneering immuno-oncology (IO) 2.0 bispecific antibodies, cadonilimab (PD-1/CTLA-4) and ivonescimab (PD-1/VEGF), as well as other proprietary high-potential anti-tumor assets, including AK117 (anti-CD47 monoclonal antibody) and AK109 (anti-VEGF monoclonal antibody), across a spectrum of advanced solid tumors. This milestone marks a strategic acceleration of Akeso's proprietary "IO 2.0 + ADC 2.0" combination platform into mid-stage clinical development.

These Phase II studies will leverage the cadonilimab and ivonescimab as foundational backbone therapies, capitalizing on their validated clinical profiles in checkpoint blockades and dual VEGF/PD-1 inhibition. The regimens center on Akeso's internally discovered next-generation ADCs while exploring synergies with the company's broader internal portfolio.

The convergence of immuno-oncology and ADC modalities has emerged as a high-conviction frontier in oncology therapy, offering the potential to overcome the limitations of monotherapy approaches – such as antigen escape, heterogeneous expression, and narrow therapeutic indices. Akeso holds a distinct global competitive advantage as the only company with two approved cancer immunotherapy checkpoint bispecific antibodies. By pairing these IO backbones with next-generation ADC candidates like AK146D1 and AK138D1, the Company is driving the next generation of combination therapy. AK146D1 and AK138D1 have been specifically designed to expand the therapeutic window and mitigate safety-related limitations of traditional ADCs. The progression of these "IO 2.0 + ADC 2.0" combinations into Phase II development is a significant step in establishing Akeso's next-generation leadership in the global oncology landscape.

AK146D1 is a first-in-class bispecific ADC engineered to simultaneously target Trop2 and Nectin4, antigens that are frequently co-expressed in epithelial-derived malignancies such as lung, breast, and bladder cancers. This dual-targeting approach is designed to enhance selectivity, address tumor heterogeneity, and overcome the resistance mechanisms common in single-target ADC therapies. AK138D1 is a next-generation ADC targeting HER3, a receptor associated with tumor progression and resistance to established EGFR and HER2 treatments in various malignancies, including ovarian, colorectal, melanoma, and prostate cancers. Early-stage data for both AK146D1 and AK138D1 have demonstrated potent anti-tumor activity and a highly manageable safety profile.

Akeso continues to extend its global IO 2.0 leadership into broader, high-impact combination strategies. Beyond the "IO 2.0 + ADC 2.0" portfolio, the Company is advancing a comprehensive portfolio of novel combination approaches aimed at addressing major unmet clinical needs. These include IO 2.0 combinations with other immune checkpoint inhibitors (ICIs), mRNA-based personalized cancer vaccines (such as AK154), DNA-based therapeutics, and additional novel therapeutic platforms. 

This milestone underscores Akeso's disciplined execution in translating proprietary platform synergies into clinical progress, positioning the Company at the forefront of next-generation global oncology innovation.