Ascentage Pharma to Present Latest Results from Six Preclinical Studies at AACR Annual Meeting 2022

SUZHOU,China and ROCKVILLE,Md.,March 9,2022 --Ascentage Pharma (6855.HK),a global biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B (CHB),and age-related diseases,today announced that the results from six preclinical studies of the company's five drug candidates: the Bcl-2 inhibitor lisaftoclax (APG-2575) and the MDM2-p53 inhibitor alrizomadlin (APG-115),two key products of the company's apoptosis-targeted pipeline as well as the FAK inhibitor APG-2449,the EED inhibitor APG-5918 and the KRAS Inhibitor APG-1842,have been selected for presentations at the American Association for Cancer Research (AACR) Annual Meeting 2022,and are already published on AACR's official website.

The AACR annual meeting is one of the world's largest and long-standing scientific gatherings in the field of cancer research. Covering some of the most cutting-edge advances in all the areas of oncology research and innovation,the annual event attracts tremendous interest from the global cancer research community. This year's AACR annual meeting will be held in the city of New Orleans,United States,on April 8-13,2022.

These six abstracts from Ascentage Pharma include:

On drug candidates lisaftoclax and alrizomadlin

Co-targeting MDM2-p53 and BCL-2 apoptosis pathways overcomes resistance conferred by acquired BCL-2 gene mutations in preclinical models

Abstract Number: 3964

Session Category: Experimental and Molecular Therapeutics

Session Title: Hematological and Pediatric Malignancy and Sarcoma Treatment Resistance

Time: 9:00 AM – 12:30 PM CST,April 13,2022

BCL-2 mutation is a key mechanism driving the drug-resistance to BCL-2 inhibitors. This study finds that dual targeting the BCL-2 and MDM2-p53 apoptotic pathways can overcome this drug resistance,thereby provide compelling rationale to future clinical studies and a potential clinical strategy for addressing resistance to BCL-2 inhibitors.

On drug candidate alrizomadlin

Inhibition of MDM2-p53 interaction by alrizomadlin (APG-115) induces pyroptotic cell death in gasdermin E (GSDME)-expressing cancer cells

Abstract Number: 2998

Session Category: Molecular/Cellular Biology and Genetics

Session Title: Non-apoptotic Cell Death / Autophagy

Time: 1:30 PM – 5:00 PM CST,April 12,2022

This study revealed a new mechanism of the MDM2-p53 inhibitor APG-115,other than apoptosis induction. The newly discovered mechanism allows APG-115 to induce pyroptotic cell death and the release of inflammatory cytokines in gasdermin E (GSDME)-expressing cancer cells.

MDM2 inhibitor alrizomadlin (APG-115) stabilizes p53 and synergizes with proteasome inhibitors in multiple myeloma

Abstract Number: 5439

Session Category: Experimental and Molecular Therapeutics

Session Title: Small Molecule Therapeutic Agents

Time: 12:00 PM – 1:00 PM CST,April 8,2022

This study shows that the MDM2-p53 inhibitor APG-115 in combination with proteasome inhibitor has synergistic antitumor activity in models of TP53 wild-type multiple myeloma.

On drug candidate APG-2449

FAK inhibitor APG-2449 and CDK4/6 inhibitor palbociclib synergistically suppress mesothelioma tumor growth via autophagy induction

Abstract Number: 2563

Session Category: Experimental and Molecular Therapeutics

Session Title: Cell Cycle,Replication Inhibitors,and Immunotherapy Agents

Time: 9:00 AM – 12:30 PM CST,2022

This study shows that in mesothelioma tumor models,the FAK inhibitor APG-2449 can suppress tumor growth via autophagy induction and has demonstrated antitumor activities,thus provide theoretical support to the design of future clinical studies.

On drug candidate APG-5918

Preclinical development of embryonic ectoderm development (EED) inhibitor APG-5918/EEDi-5273 for cancer therapy

Abstract Number: 3939

Session Category: Experimental and Molecular Therapeutics

Session Title: Emerging New Anticancer Agents

Time: 9:00 AM – 12:30 PM CST,2022

This study finds that as a potent EED inhibitor,APG-5918 can specifically suppress the H3K27me3 level in tumor cells and has demonstrated potent antitumor activity in EZH2-mutant or SMARCB1-defficient tumor cells and mouse models.

On drug candidate APG-1842

Development of covalent KRASG12C inhibitor APG-1842 for the treatment of solid tumors

Abstract Number: 2664

Session Category: Experimental and Molecular Therapeutics

Session Title: Signaling Pathway Inhibitors

Time: 9:00 AM – 12:30 PM CST,2022

This study shows that as a novel selective covalent KRASG12C inhibitor,APG-1842 can block the KRAS signaling-pathway by specially targeting the inactive (GDP bound) KRASG12C protein,demonstrating potent antitumor activity in KRASG12C-mutant tumor cells and mouse tumor models.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers,chronic hepatitis B,and age-related diseases. On October 28,2019,Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK.

Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis,or programmed cell death. The company has built a pipeline of eight clinical drug candidates,including novel,highly potent Bcl-2,and dual Bcl-2/Bcl-xL inhibitors,as well as candidates aimed at IAP and MDM2-p53 pathways,and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 Phase I/II clinical trials in the US,Australia,Europe,and China. Olverembatinib,the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML),was granted Priority Review status and a Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA),and is already approved for the indication. In addition,the olverembatinib was also granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA,and an Orphan Designation by the EU. To date,Ascentage Pharma has obtained a total of 12 ODDs from the US FDA and 1 ODD from the EU for four of the company's investigational drug candidates. Ascentage Pharma has been designated for multiple Major National R&D Projects,including five National Major New Drug Discovery and Manufacturing projects,one New Drug Incubator status,four Innovative Drug Programs,and one Major Project for the Prevention and Treatment of Infectious Diseases.

Leveraging its robust R&D capabilities,Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology,MD Anderson Cancer Center,Mayo Clinic,Dana-Farber Cancer Institute,MSD,AstraZeneca,and Pfizer. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs,in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

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,Ascentage Pharma undertakes 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.

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