[Translation] An open-label Phase Ib dose-finding and safety study of ATG-008 combined with ATG-010 in relapsed/refractory diffuse large B-cell lymphoma (RR DLBCL)

主要目的：1.确定ATG-008联合ATG-010给药在RR DLBCL中的MTD和RP2D 2.评估ATG-008联合ATG-010给药的安全性和耐受性次要目的：1.评估ATG-008联合ATG-010给药的初步疗效 2.评估ATG-008和ATG-010在联合给药中的PK特征

[Translation]

Primary objectives: 1. Determine the MTD and RP2D of ATG-008 combined with ATG-010 in RR DLBCL 2. Evaluate the safety and tolerability of ATG-008 combined with ATG-010 Secondary objectives: 1. Evaluate the preliminary efficacy of ATG-008 combined with ATG-010 2. Evaluate the PK characteristics of ATG-008 and ATG-010 in combination

Start Date21 Mar 2022

Sponsor / Collaborator

Catalent CTS LLC

[+2]

NCT05354362 / TerminatedPhase 1

An Open Label, Phase Ⅰb Study of ATG-010 in Combination With ATG-008 in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

This is an Open label, Phase Ⅰb Study of ATG-010 in Combination With ATG-008 in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma (RR DLBCL)

Start Date02 Mar 2022

Sponsor / Collaborator

Antengene Corp. Ltd.

NCT04998760 / Unknown statusPhase 2IIT

A Multi-center Clinical Study to Evaluate Dual mTORC1/2 Inhibitor (ATG 008) or Selective Inhibitor of Nuclear Export Compound (ATG-010) in Combination With Chemotherapy in Patients With Relapsed or Metastatic Ovarian Cancer, Endometrial Cancer, and Cervical Cancer

1. This is a multi-center clinical study to evaluate dual mTORC1/2 inhibitor (ATG 008) or selective inhibitor of nuclear export compound (ATG-010) in combination with chemotherapy in patients with relapsed or metastatic ovarian cancer, endometrial cancer, and cervical cancer.

Start Date03 Aug 2021

Sponsor / Collaborator

Chongqing University Cancer Hospital

100 Clinical Results associated with Onatasertib

100 Translational Medicine associated with Onatasertib

100 Patents (Medical) associated with Onatasertib

Literatures (Medical) associated with Onatasertib

27 Jun 2022·World journal of hepatology

COVID-19 liver and gastroenterology findings: An in silico analysis of SARS-CoV-2 interactions with liver molecules

Article

Author: de Oliveira, Lucca Miketen ; Teixeira, Kádima Nayara ; da Silva, Filipe Antônio França ; de Melo, Fabrício Freire ; de Souza, Cristiano de Bem Torquato ; Peiter, Gabrielle Caroline ; Dos Anjos, Valentina Nunes Fontoura ; Pagliarin, Luis Gustavo

BACKGROUND:

Coronavirus disease 19 (COVID-19) has not only been shown to affect the respiratory system, but has also demonstrated variable clinical presentations including gastrointestinal tract disorders. In addition, abnormalities in liver enzymes have been reported indicating hepatic injury. It is known that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) might infect cells via the viral receptor angiotensin-converting enzyme 2 (ACE2) which is expressed in several organs including the liver. The viral Spike glycoprotein binds to ACE2 and must be cleaved by Furin and Type 2 Serine Protease to enter the cells. After that, the Akt/mTOR signaling pathway is activated and several COVID-19 changes are triggered.

AIM:

To analyze liver and gastrointestinal symptoms and cell signaling pathways triggered by SARS-CoV-2 infection due to virus-liver interactions in silico.

METHODS:

In this in silico study, the three-dimensional structures of the Akt, mTORC1 and Furin (receptors) were selected from the Protein Data Bank (PDB) and the structures of inhibitors (ligands) MK-2206, CC-223 and Naphthofluorescein were selected from PubChem and ZINC databases. Ligand files were downloaded as 2D structures and converted to optimized 3D structures using ViewerLite 4.2 software. Marvin Sketch^® software was used to calculate prediction of the protonated form of inhibitors in a physiological environment (pH 7.4). AutoDock Tools (ADT) software was used to calculate and delimit the Grid box used in the molecular docking of each structure selected in the PDB. In addition, protonated ligands were prepared for molecular docking using ADT software. Molecular docking was performed using ADT software tools connected to Vina software. Analysis of the amino acid residues involved in ligand interactions, as well as ligand twists, the atoms involved in interactions, bond type and strength of interactions were performed using PyMol^® and Discovery Studio^® (BIOVIA) software.

RESULTS:

Molecular docking analysis showed that the mTORC1/CC-223 complex had affinity energy between the receptor and ligand of -7.7 kcal/moL with interactions ranging from 2.7 to 4.99 Å. There were four significant chemical bonds which involved two of five polypeptide chains that formed the FKBP12-Rapamycin-Binding (FRB) domain. The strongest was a hydrogen bond, the only polar interaction, and Van der Waals interactions shown to be present in 12 residues of mTORC1's FRB domain. With regard to the Akt/MK-2206 complex there were three Van der Waals interactions and 12 chemical bonds in which seven residues of Akt were involved with all five rings of the MK-2206 structure. In this way, both ASP 388 and GLN 391 bind to the same MK-2206 ring, the smaller one. However, LYS 386 had four chemical bonds with the inhibitor, one with each structure ring, while LYS 387 binds two distinct rings. One of the MK-2206 inhibitor's rings which binds to LYS 387 also binds simultaneously to ILE 367 and LEU 385 residues, and the fifth ring of the structure was involved in a bond with the ALA 382 residue. The hydrogen bonds were the shortest bonds in the complex (2.61 and 3.08 Å) and all interactions had an affinity energy of -8.8 kcal/moL. The affinity energy in the Furin/Naphhofluorescein complex was -9.8 kcal/moL and involved six interactions ranging from 2.57 to 4.98 Å. Among them, two were polar and the others were non-polar, in addition to twelve more Van der Waals interactions. Two distinct hydrogen bonds were formed between Furin and its inhibitor involving GLN 388 and ALA 532 residues. ALA 532 also binds to two distinct rings of Naphthofluorescein, while TRP 531 residue has two simultaneous bonds with the inhibitor.

CONCLUSION:

Liver infection and signaling pathways altered by SARS-CoV-2 can be modulated by inhibitors that demonstrate significant interaction affinity with human proteins, which could prevent the development of infection and symptoms.

01 Feb 2022·EJHaem

Phase Ib study of combinations of avadomide (CC‐122), CC‐223, CC‐292, and rituximab in patients with relapsed/refractory diffuse large B‐cell lymphoma

Article

Author: Kenkre, Vaishalee P. ; Sangha, Randeep ; Pourdehnad, Michael ; Advani, Ranjana ; Cassier, Philippe A. ; Hege, Kristen ; Ribrag, Vincent ; Haeske, Harald ; Hagner, Patrick R. ; Chandler, Jason C. ; Flinn, Ian W. ; Uttamsingh, Shailaja ; Santoro, Armando ; Boccomini, Carola ; Corradini, Paolo ; Kaplan, Jason ; Michelliza, Sophie ; Kuruvilla, John ; Gandhi, Anita K. ; Shen, Frank ; Chavez, Julio C. ; Isufi, Iris

Abstract:

There is a need for additional treatment options for patients with relapsed or refractory diffuse large B‐cell lymphoma (DLBCL) who do not benefit from available therapies. We examined combinations of the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC‐122), the selective, ATP‐competitive mammalian target of rapamycin kinase inhibitor CC‐223, and the potent, selective, covalent Bruton tyrosine kinase inhibitor CC‐292 in patients with relapsed/refractory (R/R) DLBCL.In the multicenter, phase Ib CC‐122‐DLBCL‐001 study (NCT02031419), the dose‐escalation portion explored combinations of CC‐122, CC‐223, and CC‐292 administered as doublets or triplets with rituximab in patients with chemorefractory DLBCL. Primary endpoints were safety, tolerability, and dose‐limiting toxicities; additional endpoints included pharmacokinetics, pharmacodynamics, biomarkers, and preliminary efficacy.As of December 1, 2017, 106 patients were enrolled across four cohorts. The median age was 65 years (range 24–84 years), and patients had a median of 3 (range 1–10) prior to regimens. A total of 101 patients (95.3%) discontinued, most commonly due to disease progression (49.1%). The most common any‐grade adverse events (AEs) across treatment arms were gastrointestinal and hematologic; the most common grade 3/4 AEs were hematologic. CC‐122 was well tolerated, with no unexpected safety concerns. Preliminary efficacy was observed in three of four treatment arms. CC‐122 plus rituximab was considered suitable for dose expansion, whereas CC‐223 and CC‐292 combinations were associated with enhanced toxicity and/or insufficient improvement in responses.CC‐122 plus rituximab was well tolerated, with preliminary antitumor activity in patients with R/R DLBCL. This innovative study demonstrates the feasibility of assessing the tolerability and preliminary efficacy of novel combinations utilizing a multi‐arm dose‐finding design.

02 Jan 2019·Xenobiotica; the fate of foreign compounds in biological systems

Absorption, distribution, metabolism, and excretion of mTOR kinase inhibitor CC-223 in rats, dogs, and humans

Article

Author: Surapaneni, Sekhar ; Atsriku, Christian ; Yerramilli, Usha ; Tong, Zeen ; Nissel, Jim ; Li, Yan ; Wang, Xiaomin

1. The absorption, distribution, metabolism, and excretion of CC-223 were studied following a single oral dose of [¹⁴C]CC-223 to rats (3 mg/kg; 90 μCi/kg), dogs (1.5 mg/kg; 10 μCi/kg), and healthy volunteers (20 mg; 200 nCi). 2. CC-223-derived radioactivity was widely distributed in rats. Excretion of radioactivity was rapid and nearly complete from rats (87%), dogs (78%), and humans (97%). Feces was the major excretion pathway for rats (67%) and dogs (70%), whereas urine (57.6%) was the major elimination route for humans. Urine and bile each contained approximately 20% administered radioactivity in rats, whereas bile (20%) played a more important role than urine (<10%) in the excretion of absorbed radioactivity in dogs. Based on excretion data, CC-223 had good absorption, with greater than 56%, 29%, and 57% of the oral dose absorbed in rats, dogs, and humans, respectively. 3. CC-223 was the prominent radioactive component in circulation of rats (>71% of the exposure to total radioactivity) and dogs (≥45.5%), whereas M1 (76.5%) was the predominant circulating metabolite in humans. M1 and M1-derived metabolites accounted for >66% of human dose. CC-223 was extensively metabolized in rats, dogs, and humans through glucuronidation, O-demethylation, oxidation, and combinations of these pathways.

News (Medical) associated with Onatasertib

24 May 2024

·www.prnewswire.com

Antengene To Present One Oral and Four Abstracts at ASCO 2024

Oral Presentation：a Phase II study of ATG-008 (mTORC1/2 Inhibitor) combined with PD-1 antibody in patients with cervical cancer Three Poster presentations: Phase I/II studies of ATG-031 (anti-CD24 monoclonal antibody), ATG-022 (Claudin 18.2 antibody-drug conjugate), and selinexor (XPO1 Inhibitor) Journal Publication: the first-in-human Phase I dose-escalation study of ATG-017 (ERK1/2 inhibitor) in patients with advanced solid tumors SHANGHAI and HONG KONG, May 23, 2024 /PRNewswire/ -- Antengene Corporation Limited ( " Antengene ", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, today announced one oral presentation, three poster presentations and a journal publication at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place from May 31st to June 4th at the McCormick Place Convention Center in Chicago, IL, the United States. Details of the Oral Presentation: ATG-008 (mTORC1/2 Inhibitor) Title: A phase I/II study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors: Cervical cancer cohort Abstract: 5509 Session: Clinical Science Symposium – Stronger Together: Novel Combinations Across the Gynecologic Cancer Spectrum Date: June 1, 2024 Time: 1:15 PM - 2:45 PM (Central Daylight Time) 2:15 AM - 3:45 AM, June 2, 2024 (Beijing Time) 31 checkpoint inhibitor (CPI)-naïve cervical cancer patients who previously had at least one systemic line of chemotherapy were enrolled in the TORCH-2 study as of Oct 20th 2023. ATG-008 (Onatasertib; oral TORC1/2 inhibitor) combined with toripalimab (anti-PD-1 antibody) showed promising anti-tumor activity and acceptable tolerability in cervical cancer patients, achieving an overall response rate (ORR) of 53.3% and a disease control rate of 86.7%. In general, ATG-008 in combination with toripalimab are very well tolerated. The most common grade ≥ 3 treatment-related adverse events (TRAEs) included rash (12.9%), decreased lymphocyte count (9.7%), and decreased platelet count (6.5%). Encouraging response rates and disease stabilization were observed in patients, regardless of PD-L1 expression, with further data being collected in an ongoing expansion cohort for CPI-treated cervical cancer. Details of the Poster Presentations: ATG-031 (anti-CD24 monoclonal antibody) Title: A first-in-human phase I study of ATG-031, anti-CD24 antibody, in patients with advanced solid tumors or B-cell non-Hodgkin lymphomas (PERFORM) Abstract: TPS2691 Session: Developmental Therapeutics—Immunotherapy Date: June 1, 2024 Time: 9:00 AM - 12:00 PM (Central Daylight Time) 10:00 PM, June 1 - 1:00 AM, June 2, 2024 (Beijing Time) ATG-031 is a first-in-class CD24 antibody that promotes cancer cell phagocytosis and T cell activity by disrupting the CD24-Siglec-10 interaction on macrophages, while also triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The Phase I PERFORM study is designed to evaluate the safety and preliminary efficacy of ATG-031 in patients with advanced solid tumors or B-cell non-Hodgkin's lymphoma, employing a dose-escalation phase with a Bayesian Optimal Interval (BOIN) design and a dose-expansion phase with two or more dose levels to determine the recommended phase II dose (RP2D). As of April 2024, the study is underway in 4 U.S. sites, and the first dose level has been cleared. ATG-022 (Claudin 18.2 Antibody-drug Conjugate) Title: An open-label, multicenter, phase I study of ATG-022 in patients with advanced/metastatic solid tumors (CLINCH) Abstract: 3032 Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Date: June 1, 2024 Time: 9:00 AM - 12:00 PM (Central Daylight Time) 10:00 PM, June 1 - 1:00 AM, June 2, 2024 (Beijing Time) ATG-022 is a Claudin 18.2 (CLDN 18.2)-targeting antibody-drug conjugate (ADC) with sub-nM high affinity that showed promising tumor inhibition activity in vitro and in vivo. The CLINCH Phase I trial is assessing its safety, tolerability, and efficacy in patients with advanced/metastatic solid tumors. As of October 9th, 2023, 10 patients have been enrolled, receiving doses ranging from 0.3 to 2.4 mg/kg. The most common grade ≥ 3 TRAEs included nausea, vomiting, and decreased appetite, each occurring in 30% of patients. No dose-limiting toxicities (DLTs) were reported. Preliminary efficacy data among 7 gastric cancer patients across multiple doses in the Phase I dose escalation demonstrated one complete response (CR) in a patient with gastric cancer (2.4 mg/kg, CLDN 18.2-negative) and one partial response (PR) in another patient (1.8 mg/kg, CLDN 18.2 expression undetermined). ATG-022 demonstrated tolerability, safety, and potential anti-tumor activity. A Phase II trial is currently enrolling patients with gastric cancer and other solid tumors. Selinexor (XPO1 Inhibitor) Title: Selinexor combined with tislelizumab in patients with relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL): Results of dose-escalation of cohort C, from a multicenter, single-arm, phase I/II study (TOUCH) Abstract: 7065 Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia Date: June 3, 2024 Time: 9:00 AM - 12:00 PM (Central Daylight Time) 10:00 PM, June 3 - 1:00 AM, June 4, 2024 (Beijing Time) The Phase I/II TOUCH study is investigating selinexor combined with different drugs in relapsed/refractory extranodal NK/T-cell lymphoma (R/R ENKTL). Cohort C of the study aims to evaluate the safety, tolerability and preliminary efficacy of selinexor in combination with anti-PD-1 antibody tislelizumab. As of December 25th, 2023, 12 patients were enrolled, with no DLTs observed, and the maximum tolerated dose (MTD) was not reached. The most common adverse events included asthenia, neutropenia, and nausea/vomiting. Grade ≥ 3 adverse events occurred in 58.3% of patients. The ORR was 72.7% among 11 efficacy evaluable patients, including a CR rate of 36.4%. The combination showed a tolerable safety profile and promising efficacy. Details of the Journal Publication: ATG-017 (ERK1/2 Inhibitor) Title: Results of a first-in-human, dose-escalation phase I study of the ERK1/2 inhibitor ATG-017 in patients with advanced solid tumors Abstract: e15114 Session: Publication Only: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology ATG-017, an oral and selective ERK1/2 inhibitor, was evaluated in a Phase I study to assess safety, pharmacokinetics, and MTD in patients with refractory advanced solid tumors. At the 20 mg BID level, no DLTs were observed, and pharmacokinetic analysis revealed effective ERK inhibition at this dose. Common treatment-emergent adverse events (TEAEs) were consistent with previously reported toxicities with other ERK pathway inhibitors (gastrointestinal, skin, and ocular adverse events). Efficacy data showed that one patient (4.8%) achieved a PR, while 8 patients (38%) achieved stable disease (SD). 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, Macau 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, 2023, 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

Phase 1Clinical ResultASCOImmunotherapyPhase 2

25 Apr 2024

·www.prnewswire.com

Antengene Announces One Oral and Three Poster Presentations at ASCO 2024

Oral session：ATG-008 (mTORC1/2 Inhibitor) combined with PD-1 antibody in Phase II studies for cervical cancer Three Poster presentations: Phase I/II studies for ATG-031 (anti-CD24 monoclonal antibody) and ATG-022 (Claudin 18.2 antibody-drug conjugate) and selinexor (XPO1 Inhibitor) SHANGHAI and HONG KONG, April 25, 2024 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage 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 four abstracts (including one oral presentation and three poster presentations) at the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting, taking place from May 31st to June 4th at the McCormick Place Convention Center in Chicago, IL, the United States. Details of the Oral Presentation: ATG-008 (mTORC1/2 Inhibitor) Title: A phase I/II study of the TORC1/2 inhibitor onatasertib combined with toripalimab in patients with advanced solid tumors: Cervical cancer cohort Abstract: 5509 Session: Clinical Science Symposium – Stronger Together: Novel Combinations Across the Gynecologic Cancer Spectrum Date: June 1, 2024 Time: 1:15 PM - 2:45 PM (Central Daylight Time) 2:15 AM - 3:45 AM, June 2, 2024 (Beijing Time) Details of the Poster Presentations: ATG-031 (anti-CD24 monoclonal antibody) Title: A first-in-human phase I study of ATG-031, anti-CD24 antibody, in patients with advanced solid tumors or B-cell non-Hodgkin lymphomas (PERFORM) Abstract: TPS2691 Session: Developmental Therapeutics—Immunotherapy Date: June 1, 2024 Time: 9:00 AM - 12:00 PM (Central Daylight Time) 10:00 PM, June 1 - 1:00 AM, June 2, 2024 (Beijing Time) ATG-022 (Claudin 18.2 Antibody-drug Conjugate) Title: An open-label, multicenter, phase I study of ATG-022 in patients with advanced/metastatic solid tumors (CLINCH) Abstract: 3032 Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology Date: June 1, 2024 Time: 9:00 AM - 12:00 PM (Central Daylight Time) 10:00 PM, June 1 - 1:00 AM, June 2, 2024 (Beijing Time) Selinexor (XPO1 Inhibitor) Title: Selinexor combined with tislelizumab in patients with relapsed or refractory extranodal NK/T-cell lymphoma (R/R ENKTL): Results of dose escalation of cohort C, from a multicenter, single-arm, phase I/II study (TOUCH) Abstract: 7065 Session: Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia Date: June 3, 2024 Time: 9:00 AM - 12:00 PM (Central Daylight Time) 10:00 PM, June 3 - 1:00 AM, June 4, 2024 (Beijing Time) 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, Macau 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, 2023, 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

Phase 1ImmunotherapyASCOPhase 2Drug Approval

22 Mar 2024

·www.prnewswire.com

Antengene Announces Full Year 2023 Financial Results, Highlights Clinical Progress Across First-in-Class, Best-in-Class Pipeline

Promising clinical activities and efficacies during dose escalations for four lead global rights programs targeting CD24, Claudin 18.2, CD73, and PD-L1/4-1BB Positive, differentiated cervical cancer data advancing mTORC1/2 inhibitor on registrational track for APAC markets RMB1.188 billion cash expected to support planned operations SHANGHAI and HONG KONG, March 22, 2024 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for cancer, today announced its full year results for the period ended December 31, 2023, and provided an update on the impressive progress of its clinical development pipeline over the last several months. "2023 has been a breakout year for Antengene, with excellent pipeline momentum across multiple first/best-in-class programs marked by encouraging clinical activities and efficacies during dose escalations for our four lead global-rights programs, namely ATG-031, ATG-022, ATG-037, and ATG-101 which are designed to target CD24, Claudin 18.2, CD73, and PD-L1/4-1BB. With respect to our APAC-rights programs, our second generation mTORC1/2 inhibitor ATG-008 has made steady progress towards registrational path for the indication of cervical cancer, complemented by the inclusion of XPOVIO® in the 2023 China National Reimbursement Drug List. Furthermore, we have entered into a partnership with Hansoh Pharma, a leading Chinese pharmaceutical company, for the commercialization of XPOVIO® in the Mainland of China," said Dr. Jay Mei, Antengene 's Founder, Chairman and C EO . "Looking into 2024 and beyond, we are confident that out four lead global rights programs will continue to deliver encouraging results and emerge as category leaders. Our current cash balance totaling RMB1.188 billion is expected to fund planned operations and product development. We look forward to report on our progress throughout the year, starting with the presentation of several abstracts at the American Association for Cancer Research Annual Meeting (AACR 2024)." 1. Momentous clinical development across four lead global-rights programs ATG-031 (anti-CD24 monoclonal antibody): Promising Activity at Starting Doses: ATG-031 is the first-in-class humanized anti-CD24 monoclonal antibody to enter the clinic for cancer in the U.S. ATG-031 acts by inhibiting the "don't eat me" signal while stimulating the "eat me" signal and enhances macrophage-mediated phagocytosis of cancer cells. Phase I "PERFORM" study: To date, a total of 5 late-stage cancer patients have been treated with ATG-031 in the Phase I dose escalation study. To date, no dose-limiting toxicities (DLTs) have been observed among the 5 patients. Tumor shrinkage based on CT scan was observed in one heavily pre-treated patient (7 prior lines of therapy). Key study sites include four major U.S. cancer centers: The University of Texas MD Anderson Cancer Center, the University of California San Francisco, the University of Colorado, and Yale University Cancer Center. Next ATG-031 Milestone: Completion of the dose escalation portion of the Phase I "PERFORM" Study in H1 2025. ATG-022 (Claudin 18.2 antibody-drug conjugate, "ADC"): Potential to Target Claudin 18.2 Low Expressors: ATG-022 is differentiated by its potential ability to be active across a range of Claudin 18.2 expression levels, including in low expressors. Antengene has also developed a companion diagnostic assay to support the clinical program. The ADC has been awarded two Orphan Drug Designations (ODD) by the U.S. Food and Drug Administration (FDA) for treatment of gastric and pancreatic cancers. Phase I "CLINCH" study: To date, 7 gastric cancer patients (without pre-screening patients' Claudin 18.2 expression levels) have been treated with ATG-022. Antengene has observed one complete response (CR) and one partial response (PR) in 2 patients with metastatic gastric cancer. In the 2.4 mg/kg dose cohort, one patient with extremely low expression of Claudin 18.2 achieved CR, while one patient from the 1.8 mg/kg dose cohort achieved PR. The study has already completed the dose escalation portion and initiated the dose expansion portion. Next ATG-022 Milestone: Clinical data readout of Phase I "CLINCH trial", including preliminary efficacy and safety in H2 2024. ATG-037 (CD73 small molecule inhibitor): Early Combination Activity Shown Potential in Reversing Prior PD-1 Resistance: Inhibiting CD73 is intended to stop the production of adenosine, a key immunosuppressive molecule in the tumor microenvironment. As a small molecule inhibitor of CD73, ATG-037 has demonstrated pre-clinically the ability to overcome the "hook effect" that can limit efficacy and is commonly seen in anti-CD73 antibodies. Antengene entered into a global clinical collaboration with MSD and is currently evaluating this molecule in combination with the anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in patients with locally advanced or metastatic solid tumors. Phase I "STAMINA" study: In the dose escalation segment of ATG-037 combined with pembrolizumab, Antengene has observed PRs in two patients with melanoma and one patient with non-small cell lung cancer (NSCLC), all of whom were refractory to prior treatment with checkpoint inhibitors (CPIs). To date, 23 patients have been enrolled and received a first tumor assessment. Next ATG-037 Milestone: Completion of Phase I dose escalation and proceed to dose expansion in H1 2024. ATG-101 (PD-L1/4-1BB bispecific antibody): Durable Responses at Low Doses with No Off-Target Hepatotoxicity Observed and Efficacy in Cold Tumors: ATG-101's differentiated approach to targeting PD-L1 resistant cancers incorporates the T-cell co-stimulatory receptor 4-1BB. The bispecific antibody utilizes high PD-L1 affinity and conditional 4-1BB activation, to reduce the risk of hepatotoxicity. Phase I "PROBE" study: Antengene has observed a PR in a patient with metastatic colon adenocarcinoma (microsatellite stability biomarker [MSS], liver metastasis, and three prior lines of therapy). In addition, SD has been observed in two patients for longer than 1 year. Next ATG-101 Milestone: Completion of Phase I dose escalation and proceed to dose expansion in H1 2025. Progressing Early programs: Antengene continues to advance IND candidate, ATG-042 ( MTAPnull-selective PRMT5 Inhibitor), and the proprietary AnTenGagerTM "2+1" T cell engager platform. 2. Steadily progressing mid/late-stage clinical programs continue to demonstrate clinical potentials ATG-008 (mTORC1/2 small molecule inhibitor): Positive, Robust Cervical Cancer Data -The mTOR complex regulates different cellular processes and is upregulated in multiple tumors. mTORC1 and mTORC2 have to be inhibited simultaneously to maximize efficacy and minimize the development of resistance. ATG-008 was designed to inhibit both. Phase II "TORCH-2" study: ATG-008 has demonstrated positive Phase II results in cervical cancer that position the program to have a competitive profile compared to other agents approved across different global markets. The Phase II "TORCH-2" study is currently enrolling both checkpoint inhibitor (CPI)-naïve and CPI-pre-treated patients. Based on the latest data review as of March 14th, 2024, out of the 31 CPI-naïve patients who received treatment (30 had at least one tumor assessment), the objective response rate (ORR) was observed to be 53.3%, the disease control rate (DCR) was 86.7%. Among the 30 patients with prior CPI treatment (26 patients had at least one tumor assessment), the ORR was 23.1%, with a DCR of 84.6%. Next ATG-008 Milestone: Confirm registrational pathway in cervical cancer with health authorities. 3. Solidifying presence in APAC markets through accelerating commercialization Antengene and Hansoh Pharma entered into a collaboration for the commercialization of XPOVIO® in the Mainland of China in August 2023. XPOVIO® has been added to the NRDL (2023 Version) as announced on December 14th, 2023. The updated NRDL, taking effect on January 1st, 2024, will significantly improve the accessibility of XPOVIO® in Mainland of China. As of December 2023, Antengene has successfully secured XPOVIO® regulatory approvals in seven markets: Mainland of China, Taiwan China, Hong Kong China, Macau China, Australia, South Korea, and Singapore. National reimbursement has been secured in 3 markets: Mainland of China (NRDL), Australia (Pharmaceutical Benefits Scheme), and Singapore (Cancer Drug List). In June 2023, the coverage of XPOVIO® by the Australian Pharmaceutical Benefits Scheme (PBS) was extended from Xd to include both XVd and Xd regimens. . 4. Strong cash and bank balance enabling continuous growth As of December 31, 2023, the company's cash resources of about RMB1.188 billion, coupled with careful spending to support the continuous growth, development, and operations of Antengene. To learn more about the annual financial results of 2023, please see the full announcement on the "Investor Relations" section of the website. 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 11 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, Macau 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, 2023, 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

Phase 1Clinical ResultPhase 2Orphan DrugFinancial Statement

100 Deals associated with Onatasertib

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Endometrial Carcinoma	Phase 2	CN	Chongqing University Cancer Hospital	03 Aug 2021
Recurrent ovarian cancer	Phase 2	CN	Chongqing University Cancer Hospital	03 Aug 2021
Uterine Cervical Cancer	Phase 2	CN	Antengene Corp. Ltd.	23 Apr 2020
Hepatitis B	Phase 2	CN	Halo Pharmaceutical, Inc.	28 Nov 2018
Hepatitis B	Phase 2	CN	Antengene Corp. Ltd.	28 Nov 2018
Advanced Hepatocellular Carcinoma	Phase 2	CN	Antengene Corp. Ltd.	07 Aug 2018
Advanced Hepatocellular Carcinoma	Phase 2	KR	Antengene Corp. Ltd.	07 Aug 2018
Advanced Hepatocellular Carcinoma	Phase 2	TW	Antengene Corp. Ltd.	07 Aug 2018
Advanced Malignant Solid Neoplasm	Phase 2	US	Celgene Corp.	20 Jul 2010
Advanced Malignant Solid Neoplasm	Phase 2	FR	Celgene Corp.	20 Jul 2010

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04337463 (ASCO2024) Manual	Phase 1/2	Uterine Cervical Cancer \| Advanced Malignant Solid Neoplasm	31	Onatasertib	pxrtsfxsit(wjnrnzhczf) = omddtezuhv rguvapfcaz (dukzxvfvov ) View more	Positive	24 May 2024
NCT04337463 (TORCH-2, Corporate Publications) Manual	Phase 2	Uterine Cervical Cancer First line \| Second line	54	ATG-008+特瑞普利单抗 (CPI初治)	rjonjymilq(rgkzveeecl) = xcefmdfbdz orlsqfuvpp (kkirxfxbhu ) View more	Positive	17 Nov 2023
NCT04337463 (TORCH-2, Corporate Publications) Manual	Phase 2	Uterine Cervical Cancer First line \| Second line	54	ATG-008+特瑞普利单抗 (既往接受过CPI治疗)	rjonjymilq(rgkzveeecl) = pxjceyjanq orlsqfuvpp (kkirxfxbhu ) View more	Positive	17 Nov 2023
NCT04337463 (ASCO2023) Manual	Phase 1/2	Solid tumor	46	Toripalimab+ATG-008	iaxlfbntet(mkfixqwybh) = not reached rddptfmhgp (msanzpzjmy ) View more	Positive	31 May 2023
NCT04337463 (ASCO2023) Manual	Phase 1/2	Solid tumor	46	Toripalimab+ATG-008 (cervical cancer)		Positive	31 May 2023
NCT03591965 (AACR2023) Manual	Phase 2	Advanced Hepatocellular Carcinoma Second line	73	Onatasertib	bdmmlnflux(bhmjwcavat) = vehcudsfdq hkwgffxuos (iwokfcqatu ) View more	Positive	14 Apr 2023
NCT03591965 (AACR2023) Manual	Phase 2	Advanced Hepatocellular Carcinoma Second line	73	Onatasertib (45 mg QD cohort)	dhzpsnzqwd(euroacfshr) = jhbytrzkzr gmfysgybhu (bbecfzzbei ) View more	Positive	14 Apr 2023
NCT04337463 (TORCH-2, Corporate Publications) Manual	Phase 1/2	Uterine Cervical Cancer	21	Toripalimab+ATG-008	bwxjxydxjf(yhjryhiaig) = qcexxytqbw rjufyywduy (vobgmpfpao )	Positive	15 Nov 2022
NCT04337463 (TORCH-2, Corporate Publications) Manual	Phase 1/2	Uterine Cervical Cancer	21	Toripalimab+ATG-008 (PD-L1表达阳性)	bwxjxydxjf(yhjryhiaig) = elwxrnrqix rjufyywduy (vobgmpfpao )	Positive	15 Nov 2022
NCT03591965 (TORCH, Corporate Publications) Manual	Phase 2	Hepatocellular Carcinoma Second line	18	ATG-008	xxsjyembfm(psporuiecd) = cuuepmhhwu qffaodskrz (vqjwmkdtfw ) View more	Positive	15 Nov 2022
NCT04337463 (TORCH-2, ASCO2022) Manual	Phase 1/2	HR-positive/HER2-low Solid Tumors	28	ATG-008+Toripalimab	xwsvdkgfru(kpfayjwpfh) = kcsoxnpqtg qdisdlztwg (kqvxsptgdk ) View more	Positive	02 Jun 2022
NCT01177397 (Pubmed \| PLoS One) Manual	Phase 2	Neuroendocrine Tumors	47	CC-223	wtsajszijb(wqhwrcdiuc) = vlfeasjkif qdnslxrflj (xizcdjujbm, 10.4 - 28.5) View more	Positive	17 Sep 2019
NCT01177397 (Pubmed \| Cancer) Manual	Phase 1/2	HR-positive/HER2-low Solid Tumors \| Multiple Myeloma	28	CC-223	gyprtrausr(crkerjuivv) = hyperglycemia, fatigue, and rash kvpxbskcwr (utjhfbuito ) View more	Positive	01 Oct 2015

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