Tizaterkib

- ATG-017 is an oral, potent and selective small molecule ERK1/2 inhibitor. Antengene has exclusive global rights to develop, commercialize, and manufacture ATG-017 - The combination portion of the ERASER study, the first-in-human (FIH) study of ATG-017, was designed to evaluate the safety/tolerability, pharmacokinetics, and preliminary efficacy of ATG-017 combination therapy with nivolumab in patients with advanced solid tumors - The monotherapy portion of the ERASER study is currently ongoing in Australia while the combination portion will be carried out in parallel in both the U.S. and Australia SHANGHAI and HONG KONG, July 17, 2023 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene" SEHK: 6996.HK), a leading commercial-stage innovative, global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for hematology and oncology, today announced that the first patient has been dosed in the United States in the combination portion of the Phase I ERASER trial to evaluate ATG-017 plus nivolumab. The objective of the combination segment of the study is to evaluate the safety/tolerability, pharmacokinetics, and preliminary efficacy of ATG-017 combination therapy with nivolumab in patients with advanced solid tumors. ATG-017 is an oral, potent, and selective inhibitor of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). Nivolumab is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. The clinical collaboration between Antengene and Bristol Myers Squibb (BMS) to evaluate ATG-017 in combination with nivolumab (the ERASER study) builds on Antengene's preclinical data which have demonstrated that the combination of an ERK1/2 inhibitor and an immune checkpoint inhibitor (ICI) worked synergistically to produce improved efficacy in preclinical ICI-resistant in vivo murine models. "We are pleased that the first patient in the combination cohort of the ERASER study of ATG-017 in the US has been dosed. Meanwhile, the monotherapy segment of the study is progressing well as planned in Australia," said Dr. Amily Zhang, Antengene's Chief Medical Officer. "Based on the the preclinical data of ATG-017 that showed highly specific selectivity and promising activity, as well as synergistic effects in combination with ICIs, we are confident in ATG-017's potential as a best-in-class ERK1/2 inhibitor and look forward to continuing to advance this clinical program of ATG-017." "Having the first patient dosed in the combination portion of this study of ATG-017 in the U.S. marks another milestone in the development of the drug candidate. We have high hopes for ATG-017, a small molecule ERK1/2 inhibitor with great therapeutic potential in combination with PD-1/PD-L1 blockade or agents targeting signal pathways," said Dr. Jay Mei, Antengene's Founder, Chairman and CEO. "This milestone underscores Antengene's commitment to its global innovation strategies. We will press ahead with this clinical study in efforts to bring another novel, effective and safe treatment option to cancer patients worldwide." About ATG-017 ATG-017 is an oral, potent, and selective small molecule extracellular signal-regulated kinases 1 and 2 (ERK1/2) inhibitor. ERK1/2 are related protein-serine/threonine kinases that function as terminal kinases in the RAS-MAPK signal transduction cascade. This cascade regulates a large variety of cellular processes, including proliferation. The RAS-MAPK pathway is dysregulated in more than 30% of human cancers with the most frequent alterations being observed in RAS or BRAF genes across multiple tumor types. An ERK inhibitor enables the targeting of both RAS and BRAF mutant diseases. Antengene presented data at the Society for Immunotherapy in Cancer (SITC) 36th Annual Meeting & Pre-conference Programs in November 2021 detailing compelling preclinical results showing the combination of ATG-017 and an anti-PD-L1 monoclonal antibody (atezolizumab) in an aggressive immune checkpoint resistant murine cancer model rendered "cold" tumors "hot". 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. About Antengene Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of "Treating Patients Beyond Borders". Since 2017, Antengene has built a pipeline of 9 oncology assets at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. To date, Antengene has obtained 29 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 10 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in Mainland of China, Taiwan China, Hong Kong China, South Korea, Singapore and Australia. 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, 2022, and the documents subsequently submitted to the Hong Kong Stock Exchange. For more information, please contact: Investor Contacts: Donald Lung E-mail: [email protected] Mobile: +86 18420672158 PR Contacts: Peter Qian E-mail: [email protected] Mobile: +86 13062747000 SOURCE Antengene Corporation Limited

Five posters showcased progress with multiple preclinical and clinical programs, including ATG-008 (mTORC1/2 inhibitor), ATG-017 (ERK1/2 inhibitor), ATG-037 (CD73 inhibitor), ATG-031 (anti-CD24 monoclonal antibody) and ATG-034 (LILRB4 antagonist antibody) Clinical results showed promising efficacy of ATG-008 in patients with advanced HBV+ HCC, especially those who had received CPIs SHANGHAI and HONG KONG, April 17, 2023 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene" SEHK: 6996.HK), a leading innovative, global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, today 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. "The five posters we present at AACR 2023 provides Antengene with an opportunity to share a range of encouraging results including the expanded Phase II data of ATG-008 for the second-line treatment of patients with HBV+ HCC, as well as the preclinical results of ATG-017, ATG-037, ATG-031, and ATG-034,"said Dr. Bo Shan, Antengene's Chief Scientific Officer. "A highlight of the results is the promising tumor response and overall survival data from the study in patients with advanced disease as they suggest that ATG-008 monotherapy represent a promising therapeutic option for patients who have received prior systemic therapy, including PD-1/PD-L1 inhibitors. Maintaining our focus on addressing patients' unmet clinical needs, we will continue to actively explore and evaluate combinations between our existing programs and other targets and agents, with the hope of gathering sufficient rationale to support the future clinical development of these regimens." Details of the Poster Presentations: 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 a partial response ( 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%. Among them, 11 patients (61.1%) had received at least 2 prior lines of therapy and 15 patients had been exposed to an anti-PD-1/PD-L1 checkpoint inhibitor (CPI) (83.3%). The median progression-free survival (mPFS) was 3 months in the intend-to-treat (ITT) population and 5.3 months in the 45mg QD cohort. These data suggest that ATG-008 has single-agent efficacy in HBV+ HCC patients who have failed at least one prior systemic therapy, notably in the 45 mg QD dosing level, in which most patients had been previously exposed to an anti-PD-1/PD-L1 therapy. Further, the results indicate that ATG-008 has the potential in HBV+ HCC patients who have failed prior CPI therapy and support further study, particularly in patients who have failed prior anti-VEGF and anti-PD-l/PD-L1 therapy. 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) T itle : 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 T ime : 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 ( o simertinib), KRASG12C inhibitor (ATG-012), CDK4/6 inhibitor ( a bemaciclib) or PD-L1 inhibitor ( a tezolizumab), 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) T itle : Targeting CD73-Adenosine Axis for the treatment of multiple myeloma Abstract: 496 Date: April 16, 2023 T ime : 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. Antengene is currently evaluating ATG-037 in Australia and mainland of China in the Phase I STAMINA study, as a monotherapy and in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors. ATG-031 (anti-CD24 monoclonal antibody) T itle : 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 PM April 19 - 12:30 AM April 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) T itle : ATG-034, an LILRB4 antagonist antibody, reinvigorates dendritic cells and prevents tumor progression Abstract: 6384 Date: April 19, 2023 T ime : 9:00 AM – 12:30 PM (Eastern Time) 9:00 PM April 19 - 12:30 AM April 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). These results suggest that ATG-034 successfully reprogrammed tolerized DCs to an "immunogenic" state, thereby enhancing anti-tumor immunity and demonstrating potent in vivo anti-tumor efficacy compared to a benchmarking compound . About Antengene Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of "Treating Patients Beyond Borders". Since 2017, Antengene has built a pipeline of 9 oncology assets at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. To date, Antengene has obtained 28 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 9 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in Mainland of China, Taiwan,China, South Korea, Singapore and Australia. 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, see the section titled "Risk Factors" in our periodic reports filed with the Hong Kong Stock Exchange and the other risks and uncertainties described in the Company's Annual Report for year-end December 31, 2021, and subsequent filings with the Hong Kong Stock Exchange. For more information, please contact: Investor Contacts: Donald Lung E-mail: [email protected] Mobile: +86 18420672158 PR Contacts: Peter Qian E-mail: [email protected] Mobile: +86 13062747000 SOURCE Antengene Corporation Limited