Antengene presents preclinical AnTenGager D2 data at SITC 2026

SHANGHAI and HONG KONG, Nov. 9, 2026 /PRNewswire/ -- Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for autoimmune diseases, solid tumors and hematological malignancies, today announced that it has presented the latest preclinical results of its novel costimulatory T cell engager (Cos-TCE) platform AnTenGager‑D2 in a Rapid Oral Abstract Presentation at the 2026 Society for Immunotherapy of Cancer Annual Meeting (SITC 2026). The study was selected as TOP150 abstracts by the conference.

Details of the Presentation

Title: A CD2-based costimulatory T cell engager platform integrating a novel CD3γε/δε-targeting antibody and steric-hindrance-based CD3 masking

Poster: #896

Study Overview:

• CD3-based T cell engagers (TCEs) have shown promising therapeutic efficacy in the treatment of hematological malignancies. However, clinical progress in solid tumors has been slow, largely owing to tumor microenvironmental factors such as the induction of T cell exhaustion and the potential of CD3-bispecifics mediated T cell anergy and dysfunction in the absence of adequate co-stimulation.
• The CD2/CD58 axis serves as a pivotal bifunctional regulator, mediating both adhesion and co-stimulation during human T cell activation. In this study, we developed a novel costimulatory T cell engager (AnTenGager-D2) platform integrating a novel CD3γε/δε-targeting antibody, steric-hindrance-based CD3 masking, and an engineered CD2-binder, which enables conditional T cell activation via CD3 (signal 1) and CD2 (signal 2) stimulation upon TAA crosslinking, providing enhanced anti-tumor activity and a wider therapeutic index.
• ATG-109 (KLK2×CD2×CD3 AnTenGager-D2 TCE) is a candidate molecule developed based on the AnTenGager-D2 platform. In this study, we evaluated its in vitro anti-tumor activity, thermostability, pharmacokinetic profile, and in vivo anti-tumor efficacy in a prostate cancer cell derived xenograft model.

Results:

• Characterization of the parental anti-CD3 mAbs of AnTenGager-D2. By screening 6108 full-length human proteins and further 403 human heterodimers using Retrogenix's Cell Microarray Technology, AnTenGager^® parental anti-CD3 mAb showed high specificity of CD3δ+CD3ε, CD3γ+CD3ε heterodimer. AnTenGager-D2 parental anti-CD3 mAbs (ATG-CD3) demonstrated "fast-on-fast-off" binding kinetics in SPR assay. ATG-CD3 mAbs induced substantially lower cytokine release than benchmark CD3 clones.
• Engineered CD58 IgV proteins exhibit superior thermostability and enhanced TDCC activity. CD58 integrated DLL3 AnTenGagers showed enhanced T cell dependent cytotoxicity against DLL3 positive tumor cell (NCI-H524), with an IC50 value of single-digit picomoles.
• AnTenGager-D2 platform expands the safety window of co-stimulatory TCEs via appropriate structural integration of engineered CD58v protein. The platform displays limited antigen-independent T cell activation and no T cell-T cell crosslinking. Among DLL3-targeting AnTenGager-D2 TCEs, Format F2 demonstrated the largest safety window.
• ATG-109 demonstrates enhanced efficacy and low cytokine release. ATG-109 showed lower binding affinity to CD3+ Jurkat cells in the absence of KLK2 crosslinking. ATG-109 demonstrated enhanced TDCC against KLK2 positive tumor cell (VCaP) compared to benchmark and showed no non-specific cytotoxicity against KLK2-negative cells (Du145).
• ATG-109 demonstrates potent in vivo efficacy in human PBMC re-established prostate cancer cell derived xenograft model.
• ATG-109 demonstrates good thermostability and exhibits good PK profile in hFcRn mice with T1/2 of ~ 183.5h. ATG-109 demonstrated a melting temperature (Tm) of > 68 ℃ and showed good stability at 10 mg/ml evaluated by SEC-HPLC (40 ℃ for 4 weeks).

Conclusion:

AnTenGager-D2 is a proprietary platform developed by Antengene for developing next-generation co-stimulatory TCEs with enhanced efficacy and safety. ATG-109, a KLK2-targeting AnTenGager-D2 TCE, showed superior preclinical efficacy compared to a clinical benchmark. The Company will further advance these preclinical studies.