Ascentage Pharma announced that it has presented results from five preclinical studies during poster presentations at the 2025 American Association for Cancer Research (AACR) Annual Meeting, taking place April 25-30, 2025, in Chicago, Illinois, USA. These poster presentations feature five of the company's drug candidates: novel tyrosine kinase inhibitor (TKI) Olverembatinib (HQP1351), Bcl-2 inhibitor lisaftoclax (APG-2575), FAK/ALK/ROS1 TKI APG-2449, embryonic ectoderm development (EED) inhibitor APG-5918, and IAP antagonist AS03157. Detailed data presented at this year's AACR Annual Meeting are as follows: Combining Bcl-2 inhibitor venetoclax with hypomethylating agents is the standard of care for patients with AML who are older or ineligible for intensive chemotherapy.
However, resistance to venetoclax is a major clinical challenge, necessitating alternative therapeutic options. Olverembatinib, a multikinase inhibitor, targets kinases associated with leukemogenesis and venetoclax resistance in AML, including FLT3, cKIT, PDGFR, Src family kinases, PI3K, and FGFR. Lisaftoclax is an investigational, novel, selective Bcl-2 inhibitor currently being tested clinically for several hematologic malignancies, including relapsed/refractory AML.
In this study, evaluated the effects of olverembatinib combined with lisaftoclax in venetoclax-resistant (VEN-R) AML models. Summary: In VEN-R AML cell lines, the combination of olverembatinib and lisaftoclax synergistically inhibited cellular proliferation and induced cellular apoptosis. Olverembatinib in combination with lisaftoclax synergistic suppressed tumor growth in a MOLM-13-VEN-R AML xenograft model invivo.
Mechanistically, western blot analysis revealed that the combination synergistically downregulated several leukemogenic signaling pathways, including those associated with venetoclax resistance, such as FLT3, AKT, MCL-1, and activated apoptosis. In summary, olverembatinib in combination With lisaftoclax overcome venetoclax resistance in preclinical AML models, warranting further clinical investigation as a new therapeutic strategy for VEN-R AML. effects of olverembatingib (HQP1351) in combination with Bcl-2 inhibitor lISAftoclax (APG -2575) in T-cell acute lymphoblastic leukemia (T-ALL).
Abstract##: 5648. Session: Novel Antitumor Agents 3: T-ALL is a high-risk hematologic cancer arising from malignant transformation of the cancer arising from malignant transformation.
