Antengene Presents Three Novel Programs at AACR 2026, Highlighting Next-Generation ADC and AnTenGager® TCEs
Details of the Poster Presentation:
ATG-125 (B7-H3 x PD-L1 bispecific ADC)
Title: ATG-125, a novel B7H3 x PD-L1 bispecific antibody-drug conjugate, demonstrates potent antitumor efficacy by dual targeting of immune evasion and direct tumor killing
Abstract Number: 5599
Session Category: Immunology
Session Title: T Cell Engagers 2 / Antibody-Drug Conjugates 1
Date:
Time:
05:00 AM,
Location: Poster Section 8
- Introduction: B7-H3 and PD-L1 are immune checkpoint molecules broadly overexpressed across multiple solid tumors and are associated with immune evasion and poor prognosis. Although PD-1/PD-L1-directed therapies have demonstrated clinical benefit, treatment resistance remains a significant challenge. B7-H3 is also emerging as a promising ADC target due to its broad tumor expression and rapid internalization. ATG-125 is a novel B7-H3 x PD-L1 bispecific ADC designed to combine direct tumor killing with immune activation by co-targeting two complementary tumor-associated pathways in a single molecule.
- Results: ATG-125 bound to both B7-H3 and PD-L1 with high specificity and nanomolar affinity and demonstrated robust antigen-dependent internalization in dual-positive tumor cells, enabling efficient intracellular payload release. The molecule induced tumor cell apoptosis, while its parental naked antibody blocked PD-1/PD-L1 interaction and elicited IL-2 and IFN-γ production in mixed lymphocyte reaction assays. ATG-125 also enhanced T-cell activation, as reflected by an increased ratio of CD69+/CD3+ T cells in co-cultures of tumor cells and human PBMCs. In vivo, ATG-125 demonstrated sustained antitumor activity in HCC827 xenograft models, increased tumor infiltration of CD4+ and CD8+ T cells in PBMC-humanized models, and inhibited tumor growth in a dose-dependent manner in MC38-hB7H3 syngeneic models, accompanied by elevated intratumoral CD8+ T-cell infiltration.
- Conclusion: ATG-125 demonstrated synergistic IO+ADC antitumor activity through a differentiated mechanism combining enhanced internalization for payload delivery with the potential to restore anti-tumor immunity. Its compelling preclinical profile supports further development for patients with solid tumors.
ATG-106 (CDH6 x CD3 TCE)
Title: ATG-106, a novel "2+1" format CDH6-targeted T-cell Engager (TCE), shows potent T cell dependent cytotoxicity and in vivo anti-tumor efficacy
Abstract Number: 1621
Session Category: Immunology
Session Title: T Cell Engagers 1
Date:
Time:
00:00 AM,
Location: Poster Section 10
-
Introduction: CDH6 plays an important role in embryonic kidney development but has negligible expression in adult kidney tissue. Its overexpression in ovarian and renal cancers, together with limited normal tissue expression, makes CDH6 an attractive therapeutic target. However, T cell engagers in solid tumors have often been limited by insufficient efficacy and the risk of cytokine release syndrome. To address these challenges,
Antengene developed ATG-106, a novel "2+1", sterically masked CDH6 x CD3 bispecific TCE designed to deliver potent antitumor activity with the potential for a reduced CRS risk profile. - Results: ATG-106 exhibited reduced binding affinity to CD3+ cells before CDH6 crosslinking, while inducing approximately 100- to 400-fold more potent cytotoxicity against CDH6-positive tumor cells compared with a "1+1" CrossMab control TCE. The molecule demonstrated potent T cell-dependent cytotoxicity in ovarian and renal cancer models and showed low immunogenicity risk in vitro. In PBMC-humanized 786-O kidney cancer xenograft models, ATG-106 induced tumor shrinkage in all treated mice, with complete remissions observed in the 0.1 mg/kg and 0.3 mg/kg groups. ATG-106 also induced tumor shrinkage and complete remission in PBMC-humanized OVCAR-3 ovarian cancer models. Notably, pro-inflammatory cytokine levels remained very low in treated animals, suggesting low CRS risk. In non-human primate studies, the surrogate molecule ATG-106-RM was well tolerated at doses up to 10 mg/kg.
- Conclusion: ATG-106 demonstrated limited T cell binding in the absence of target cells, potent cytotoxicity against tumor cells, and encouraging in vivo efficacy in ovarian and kidney cancer models. Favorable safety findings with the surrogate molecule in non-human primates further support continued clinical development of ATG-106 as a CDH6-targeted TCE candidate.
ATG-112 (ALPPL2 x CD3 TCE)
Title: ATG-112, a novel ALPP/G x CD3 bispecific T cell engager, for the treatment of ALPP/G+ solid tumors
Abstract Number: 1620
Session Category: Immunology
Session Title: T Cell Engagers 1
Date:
Time:
00:00 AM,
Location: Poster Section 10
-
Introduction: Placental alkaline phosphatase and related placental-like/germ-cell isoforms, including ALPPL2 and ALPG, are aberrantly expressed in a range of solid tumors while being largely absent from normal adult tissues except the placenta, making them highly promising tumor-selective immunotherapy targets.
Antengene developed ATG-112, an ALPP/G x CD3 bispecific TCE based on the AnTenGager® platform in a "2+1" format, featuring bivalent antigen binding to improve low-antigen tumor recognition and a sterically masked CD3 binding arm designed to restrict T-cell activation to the tumor microenvironment. - Results: Tissue microarray IHC analysis showed that ALPP/G expression was restricted to placental tissue among normal organs and was not detected in other normal tissues, while frequent expression was observed in endometrial and ovarian cancers, with lower prevalence in bladder, gastric and pancreatic cancers. ATG-112 demonstrated high binding affinity to both ALPP/G-positive tumor cells and recombinant proteins, with EC50 and KD values in the sub-nanomolar range. It induced robust T cell-dependent cytotoxicity against target-positive cells with picomolar EC50 values, while in vitro cytokine-release assays showed minimal cytokine secretion from human PBMCs. In vitro studies also demonstrated that the spatial masking effect of ATG-112 is reversible. Immunogenicity assessment showed low immunogenic potential, and in vivo ATG-112 delivered potent tumor suppression across multiple dose levels in humanized mouse models, with low cytokine release and controllable CRS risk at efficacious doses. The program also demonstrated strong developability characteristics.
- Conclusion: ATG-112 demonstrated a compelling preclinical profile, with potent in vitro and in vivo antitumor activity and minimal cytokine release. These findings support the continued advancement of ATG-112 toward clinical development for solid tumors.
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For more information, please contact:
Investor Contacts:
E-mail: donald.lung@antengene.com
BD Contacts:
E-mail: ariel.guo@antengene.com
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