Akeso IO2.0 + ADC2.0 Strategy Makes Another Advancement: First Patient Dosed in Phase Ib/II Study of HER3 ADC (AK138D1) Combined with Ivonescimab in Lung Cancer

HER3 expression is strongly linked to the development, progression, and treatment resistance in patients with NSCLC. Traditional HER3 ADCs have faced limitations in clinical use due to toxicity concerns, and none have been approved to date. Akeso designed the next-generation HER3 ADC, AK138D1, with an unique and innovative approach that minimizes uptake in normal tissues to reduce off-target toxicity and broaden the therapeutic window. This approach also prevents surface aggregation on tumor cells to improve deep and uniform tumor penetration, effectively overcoming the binding site barrier. Early clinical studies conducted in China and Australia have demonstrated that AK138D1 monotherapy delivers potent anti-tumor activity in patients with lung cancer, along with a favorable safety profile featuring low hematologic toxicity and no reported cases of interstitial lung disease (ILD).

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. The combination of AK138D1 with ivonescimab is expected to further amplify ivonescimab's immune-activating effects. This combination enables ivonescimab to exert synergistic anti-tumor activity with the next-generation HER3 ADC, potentially delivering superior clinical efficacy across various NSCLC subtypes while maintaining a favorable safety profile.

Leveraging its technological leadership in bispecific and multi-specific antibodies, Akeso is systematically building a comprehensive global IO2.0 + ADC2.0 therapeutic matrix.

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 the Company's 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 and AK138D1, both of which have entered into Phase II clinical studies, and AK157D1 and AK158D1 (a bispecific ADC), both of which will soon enter clinical studies.

Currently, multiple Phase II clinical studies are underway evaluating ivonescimab and cadonilimab in combination with AK138D1, AK146D1, and other assets. These combination studies from Akeso's own approved therapies and pipelines continue to drive global treatment paradigms upgrades for major malignancies, including lung cancer and breast cancer.

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.

View original content:https://www.prnewswire.com/news-releases/akeso-io2-0--adc2-0-strategy-makes-another-advancement-first-patient-dosed-in-phase-ibii-study-of-her3-adc-ak138d1-combined-with-ivonescimab-in-lung-cancer-302835843.html

SOURCE Akeso, Inc.