Akeso's EGFR/TROP2 Bispecific ADC AK158D1 Wins NMPA Phase I Clearance for Advanced Solid Tumors
核心洞察
Akeso's AK158D1 (搜索), a next-generation bispecific antibody-drug conjugate targeting EGFR (搜索) and TROP2 (搜索), received Phase I clearance from China's NMPA Center for Drug Evaluation.
The trial will evaluate AK158D1 (搜索) in patients with advanced malignant solid tumors (搜索), marking Akeso's fourth clinical-stage ADC candidate.
AK158D1 (搜索) is Akeso's second bispecific ADC to enter the clinic, joining AK146D1 (搜索), AK138D1 and AK157D1 (搜索) in the company's ADC pipeline.
Akeso, Inc. (9926.HK) announced that AK158D1 (搜索), its investigational next-generation bispecific antibody-drug conjugate (ADC) targeting EGFR (搜索) and TROP2 (搜索), has secured Phase I clinical trial clearance from the Center for Drug Evaluation (CDE) under China's National Medical Products Administration (搜索) (NMPA). The trial will assess the candidate in patients with advanced malignant solid tumors (搜索).
The clearance makes AK158D1 (搜索) Akeso's fourth ADC to enter clinical development and its second bispecific ADC to reach the clinic, advancing the company's stated strategy of combining next-generation immuno-oncology (IO2.0) approaches with next-generation ADC platforms (ADC2.0).
Dual Targeting Rationale
According to the company, EGFR (搜索) (epidermal growth factor receptor) and TROP2 (搜索) (trophoblast cell surface antigen 2) constitute a highly promising target pair for bispecific ADC development, with broad co-expression across a spectrum of solid tumor types. Each target has well-validated anti-tumor mechanisms of action, and Akeso states that their dual targeting holds significant synergistic anti-tumor potential.
Akeso notes that single-target ADCs directed against either EGFR (搜索) or TROP2 (搜索) have to date been constrained by three key clinical limitations: narrow tumor coverage, off-target toxicity, and multidrug resistance. AK158D1 (搜索) is designed as a next-generation dual-targeting ADC that integrates the precise tumor recognition enabled by bispecific antibodies, a highly potent cytotoxic payload, and an enhanced safety profile, which the company describes as a potential breakthrough approach to address the shortcomings of conventional single-target ADC modalities.
Preclinical Profile
AK158D1 (搜索) is a bispecific ADC featuring a humanized antibody that dually targets EGFR (搜索) and TROP2 (搜索). Preclinical pharmacodynamic studies have shown strong antigen-binding affinity and robust in vitro and in vivo pharmacological activity, according to the company. Preclinical data for AK158D1 demonstrated potent anti-tumor activity with a favorable safety profile, supporting its potential as a novel therapeutic option for a wide range of patients, including those who are refractory to, intolerant, or ineligible for existing standard of care regimens.
ADC Portfolio and IO2.0 + ADC2.0 Strategy
AK158D1 (搜索) joins a clinical-stage ADC portfolio that includes AK146D1 (搜索) (TROP2 (搜索)/Nectin-4 (搜索)), AK138D1 (HER3 (搜索)), and AK157D1 (搜索) (B7-H3 (搜索)). Akeso states that these highly differentiated next-generation candidates are designed to address the narrow therapeutic window and safety limitations commonly associated with first-generation ADCs.
The company is advancing its IO2.0 + ADC2.0 strategy, built on proprietary bispecific and multi-specific antibody technology and centered on cornerstone IO2.0 assets including ivonescimab and cadonilimab. Akeso reports that it has two approved bispecific antibodies for cancer treatment and is actively evaluating ivonescimab and cadonilimab in combination with its proprietary next-generation ADC candidates. According to the company, global partners increasingly recognize both agents as preferred agents for combination regimens and breakthrough therapy explorations across a wide spectrum of tumor types.
Pipeline and Platform Context
Akeso, founded in 2012, describes its R&D ecosystem as anchored by proprietary technology platforms including the Tetrabody antibody platform, an AI-powered drug R&D platform, the Dual-Shield ADC technology platform, the Dual-Lock T-cell engager (TCE) technology platform, the Tissue-Smart siRNA/mRNA technology platform, and cell therapy platforms. The company maintains a pipeline of more than 50 innovative assets targeting cancer, autoimmune diseases, inflammation, metabolic disorders, and other major therapeutic areas, of which nearly 30 candidates have advanced into clinical trials, including 15 bispecific or multi-specific antibodies and bispecific ADCs. Eight innovative drugs are commercially available, and two additional drugs with three indications are currently under regulatory review for marketing approval.
Akeso cautions that its announcement contains forward-looking statements subject to significant risks and uncertainties, and that there can be no assurance that AK158D1 (搜索) or its other pipeline candidates will obtain required regulatory approvals or achieve commercial success.