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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.
About Antengene
Antengene Corporation Limited (“Antengene“, SEHK: 6996.HK) is a global, R&D-driven, commercial-stage biotech company focused on developing first-in-class/best-in-class therapeutics for diseases with significant unmet medical needs. Its pipeline spans from preclinical to commercial stages, with key investigational candidates including ATG-022 (CLDN18.2 ADC), ATG-037 (oral CD73 inhibitor), ATG-101 (PD-L1 x 4-1BB bispecific antibody), ATG-125 (B7-H3 × PD-L1 bispecific ADC), ATG-207 (αCD3-TGF-β bifunctional fusion protein), as well as T cell engager (TCE) programs developed using Antengene’s proprietary AnTenGager® platform.
AnTenGager®, is Antengene’s proprietary TCE 2.0 platform, featuring “2+1” bivalent binding for low expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize cytokine release syndrome (CRS) and enhance efficacy. These characteristics support the platform’s broad applicability across autoimmune diseases, solid tumors and hematological malignancies, with programs targeting CD19 x CD3 (ATG-201 for B cell-related autoimmune diseases; partnered with UCB), CDH6 x CD3 (ATG-106 for ovarian cancer and kidney cancer; partnered with K2 Therapeutics established by MPM BioImpact), ALPPL2 x CD3 (ATG-112 for gynecological tumors, digestive system malignancies, bladder cancer and NSCLC), LY6G6D x CD3 (ATG-110 for microsatellite-stable colorectal cancer), GPRC5D x CD3 (ATG-021 for multiple myeloma), LILRB4 x CD3 (ATG-102 for acute myeloid leukemia and chronic myelomonocytic leukemia) and FLT3 x CD3 (ATG-107 for acute myeloid leukemia).
To date, Antengene has obtained 35 investigational new drug (IND) approvals in the U.S. and Asia, and obtained new drug application (NDA) approvals in 10 Asia Pacific markets. Its lead commercial asset, XPOVIO® (selinexor), is approved in the Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia, and has been included in the national insurance schemes in five of these markets (Mainland of China, Taiwan China, Australia, South Korea and Singapore).
Forward-looking statements
The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, please see the other risks and uncertainties described in the Company’s Annual Report for the year ended December 31, 2025, and the documents subsequently submitted to the Hong Kong Stock Exchange.
For more information, please contact:
PR / IR Contacts:
Peter Qian
E-mail: peter.qian@antengene.com
BD Contacts:
Ariel Guo
E-mail: ariel.guo@antengene.com
