Akeso Advances IO2.0 + ADC2.0 Strategy: First Patient Dosed in Phase II Study of TROP2/Nectin-4 Bispecific ADC (AK146D1) Combined with Ivonescimab in Breast Cancer

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.

About AK146D1 (TROP2/Nectin4 Bispecific ADC)

AK146D1 is an innovative bispecific antibody-drug conjugate (bsADC) developed by Akeso. It is composed of a bispecific antibody that simultaneously targets TROP2 and Nectin4, conjugated via a cleavable MC-AAA linker (maleimide-alanine-alanine-alanine) to the topoisomerase I inhibitor DXd.

Early research results indicate that AK146D1 for injection demonstrates potent biological activity and a favorable safety profile. A Phase II clinical study evaluating AK146D1 in combination with cadonilimab and ivonescimab for the treatment of multiple solid tumors is currently underway. This study represents an important component of Akeso's IO2.0 + ADC2.0 strategy.

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 the 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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