Antengene Corporation Limited announced the presentation of five posters at the American Association for Cancer Research Annual Meeting 2023 Meetings (AACR 2023), taking place from April 14th to 19th at the Orange County Convention Center in Orlando, Florida, the United States. ATG-008 (mTORC1/2 inhibitor): Title: Result of an open-label phase 2 trial of dual TORC1/TORC2 inhibitor onatasertib(ATG-008) in HBV+ advanced hepatocellular carcinoma(HCC) subjects who have received at least one prior line of systemic therapy(TORCH), Abstract: CT150, Date: April 17, 2023, Time: 1:30 PM - 5:00 PM (Eastern Time), 1:30 AM - 5:00 AM, April 18, 2023 (Beijing Time). This Phase II study was designed to evaluate the pharmacokinetics, safety and efficacy of ATG-008 in patients with advanced hepatitis B virus (HBV) positive hepatocellular carcinoma (HCC).

73 patients with HBV+, unresectable and refractory HCC were enrolled to receive ATG-008 at one of the four dose levels. Data from this study showed that 3 subjects achieved apartialresponse(PR), all in the 45 mg QD monotherapy cohort. A total of 18 patients were enrolled in this cohort that achieved an objective response rate (ORR) of 16.7%.

ATG-008 is being evaluated in the Phase II TORCH-2 study in patients with cervical cancer and other solid tumors. ATG-017 (ERK1/2 inhibitor): Title: Synergistic effects of the combination of ERK1/2 with EGFR, KRASG12C, CDK4/6, and PD-L1 inhibition for cancer treatment, Abstract: 5499, Date: April 18, 2023, Time: 1:30 PM – 5:00 PM (Eastern Time), 1:30 AM - 5:00 AM, April 19, 2023 (Beijing Time). This preclinical study was designed to test the in vivo anti-tumor effects induced by the combination of ATG-017, with EGFR inhibitor (osimertinib), KRASG12C inhibitor (ATG-012), CDK4/6 inhibitor (abemaciclib) or PD-L1 inhibitor (atezolizumab), in preclinical tumor models including three models of non-small cell lung cancer (NSCLC) (with EGF-R and KRAS mutations), and one model of T-cell lymphoma (resistant to anti-PD-L1) for assessing the tumor growth inhibition (TGI) and the presence of tumor infiltrating lymphocytes (TILs).

According to the results, ATG-017 demonstrated significant TGI (>60%) in the NSCLC models. In the T-cell lymphoma model, the combination of ATG-017 and the PD-L1 inhibitor, atezolizumab, showed significant tumor growth inhibition. Furthermore, that combination induced increased the infiltration of anti-tumor TILs, suggesting a potential role for ATG-017 in changing "cold" tumors to "hot".

These data suggest that the combination of ATG-017 with EGFR, KRASG12C, CDK4/6, and PD-L1 inhibitors have strong synergism and significantly improved TGI, thus represent promising therapeutic strategies for cancer patients. Antengene is evaluating ATG-017 in the Phase I ERASER study, as monotherapy and in combination with nivolumab, in patients with advanced solid tumors and hematological malignancies in Australia and the U.S. ATG-037 (CD73 inhibitor): Title: Targeting CD73-Adenosine Axis for the treatment of multiple myeloma, Abstract: 496, Date: April 16, 2023, Time: 1:30 PM – 5:00 PM (Eastern Time), 1:30 AM - 5:00 AM, April 17, 2023 (Beijing Time). This preclinical study was designed to evaluate the potential of ATG-037 in treating multiple myeloma (MM).

CD73 is a cell surface enzyme which is highly expressed in the tumor microenvironment and enables the conversion of ATP to adenosine, promoting the progression of cancer by inhibiting T-cells, natural killer (NK) cells, and dendritic cells (DCs), and inducing and enhancing the function of immunosuppressive cell types. ATG-037's ability to inhibit the activity of CD73 was evaluated in enzyme inhibition and T cell proliferation and activation assays. In vivo efficacy was assessed in syngeneic myeloma models.

Results showed complete inhibition of CD73 with ATG-037, without a "hook effect" compared to another industry benchmark antibody program. In addition, ATG-037 completely restored the function of activated T-cells and CAR-T cells from AMP-mediated T-cell suppression, suggesting a potential application in CAR-T cell therapy. In addition, the treatment with ATG-037 resulted in significant TGI compared to vehicle controls.

These data suggest that ATG-037 has single agent anti-myeloma efficacy, thus making this abstract the first report of in vivo efficacy study of a CD73 inhibitors in myeloma animal models. ATG-031 (anti-CD24 monoclonal antibody): Title: ATG-031, a first-in-class humanized anti-CD24 antibody, demonstrates potent in vivo efficacy and repolarizes tumor-associated macrophages in the TME. Abstract: 6641.

Date: April 19, 2023. Time: 9:00 AM – 12:30 PM (Eastern Time). 9:00 PMApril 19 - 12:30 AMApril 20, 2023 (Beijing Time).

This preclinical study was designed to evaluate the in vivo efficacy of ATG-031 and explored its pharmacodynamic effects. Data showed that ATG-031 monotherapy produced robust, 60-100% TGI, with increased, synergistic tumor regression from the combination of ATG-031 with oxaliplatin (chemotherapy) or atezolizumab (CPI), evaluated in one of the murine models. Flow cytometry analysis shows that ATG-031 increases T cell (CD4/CD8) tumor infiltration and significantly lower population of Treg cells in the tumor microenvironment.

These results suggest that the first-in-class antibody, ATG-031, specifically binds to CD24 with nM affinity and blocks the interaction of CD24 and Siglec-10. ATG-031 induces efficient phagocytosis with a picomolar EC50, stimulating pro-inflammatory cytokines production by macrophages. ATG-034 (LILRB4 antagonist antibody): Title: ATG-034, an LILRB4 antagonist antibody, reinvigorates dendritic cells and prevents tumor progression.

Abstract: 6384. Date: April 19, 2023. Time:9:00 AM – 12:30 PM (Eastern Time).

9:00 PMApril 19 - 12:30 AMApril 20, 2023 (Beijing Time). This preclinical study was designed to evaluate ATG-034, an antibody targeting LILRB4, as a potential immunotherapy. The antibody was tested using SPR, ELISA and FACS analysis to assess its ability to bind to LILRB4, block its interaction with its ligand, fibronectin, and reinvigorate DCs to an "immunogenic" state.

According to the data, ATG-034 demonstrated single-digit nanomolar affinity and blocked the interaction of LILRB4 with its target ligand, fibronectin and completely reversed fibronectin-mediated suppression of tolerized DC activation (TolDC), evidenced by increased TNF-a production. In addition, the antibody reprogrammed DCs to become immunogenic, as measured by the up regulation of several key co-stimulatory molecules (CD86, HLA-DR and HLA-ABC) and down-regulation of an M2 biomarker (CD206).