Akeso's Next-Generation HER3 ADC AK138D1 Combined with Ivonescimab: First Patient Enrolled in Phase Ib/II Breast Cancer Study, Advancing the IO2.0 + ADC2.0 Strategy

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.

About AK138D1

Injectable AK138D1 is a HER3-targeted antibody-drug conjugate (ADC), with a fully humanized anti-HER3 IgG1 antibody, patritumab. It is conjugated to the topoisomerase I inhibitor DXd through a cleavable linker, MC-AAA (maleimide-alanine-alanine-alanine). After binding to HER3 on tumor cells, the ADC is internalized into the tumor cells, where the linker is cleaved, releasing the membrane-permeable DXd. This leads to DNA damage and subsequent cell apoptosis. Early study results have shown that AK138D1 possesses potent biological activity and a favorable safety profile. A phase II clinical trial is currently ongoing to investigate AK138D1 combined with cadonilimab and ivonescimab in patients with solid tumors. This regimen is a critical part of Akeso's IO2.0 + ADC 2.0 combination approach.

About Akeso

Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, Akeso has built a comprehensive R&D innovation ecosystem anchored by its proprietary Tetrabody antibody technology platform, AI-powered drug R&D platform, Dual-Shield ADC technology platform, Dual-Lock T-cell engager (TCE) technology platform, Tissue-Smart siRNA/mRNA technology platform, and cell therapy technology platforms.

Backed by world-class GMP manufacturing facilities and a highly efficient, integrated commercialization system, Akeso has developed into a globally competitive biopharmaceutical enterprise. Leveraging its fully integrated, multi-functional platform, the company maintains a robust pipeline of more than 50 innovative assets targeting cancer, autoimmune diseases, inflammation, metabolic disorders, and other major therapeutic areas. Of these, 27 candidates have advanced into clinical trials—including 15 bispecific or multispecific antibodies and bispecific ADCs—and 8 innovative drugs have reached commercial stage.

Through efficient and groundbreaking R&D, Akeso integrates premier global resources to develop transformative medicines, deliver high-quality, affordable therapeutic antibodies to patients worldwide, and generate sustained commercial and societal value as it strives to become a global leader in biopharmaceutical innovation.

Forward-Looking Statements

This announcement by Akeso, Inc. (9926.HK, "Akeso") contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso's management and are subject to significant risks and uncertainties. These statements are not intended to form the basis of any investment decision or any decision to purchase securities of Akeso. There can be no assurance that the drug candidate(s) indicated in this announcement or Akeso's other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in P.R.China, the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Akeso's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the Akeso's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law.

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