Ascentage Pharma to Present Latest Results from Six Preclinical Studies at AACR Annual Meeting 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, April 12, 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, April 13, 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, April 12, 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.

Source: Ascentage Pharma