lisaftoclax (APG-2575) / Ascentage Pharma - LARVOL DELTA

Thirteen Studies of Ascentage Pharma’s Assets Including Olverembatinib and Lisaftoclax Selected for Presentations at 2025 European Hematology Association Annual Congress (GlobeNewswire) - "Ascentage Pharma...announced that 13 studies of its core assets - including the novel drug olverembatinib (HQP1351), the investigational Bcl-2 inhibitor lisaftoclax (APG-2575), and the investigational EED inhibitor APG-5918 - will be featured in an oral presentation, multiple poster presentations and multiple online publications at the 2025 European Hematology Association (EHA) Annual Congress taking place in Milan, Italy, from June 12-15, 2025."

Clinical data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Chronic Myeloid Leukemia • Lymphoma

Phase 1b/2 study of lisaftoclax (APG-2575) combined with azacitidine (AZA) in patients (pts) with treatment-naïve (TN) or prior venetoclax (VEN)-exposed myeloid malignancies. (ASCO 2025) - P1/2 | "LISA at different dose regimens combined with AZA provides promising treatment options for pts with HR-MDS or AML. No DLTs occurred. The MTD was not reached."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Febrile Neutropenia • Hematological Malignancies • Infectious Disease • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock • Thrombocytopenia

Live from ASCO 2025 | Ascentage Pharma Presents Clinical Data on Bcl-2 Inhibitor Lisaftoclax in Venetoclax-Refractory Patients in Oral Report (GlobeNewswire) - P1b/2 | N=24 | NCT04964518 | Sponsor: Ascentage Pharma Group Inc. | "As of the data cutoff in April 2025, 22 of 28 venetoclax-refractory patients with R/R AML/ Mixed Phenotype Acute Leukemia (MPAL) were efficacy-evaluable, among whom, the overall response rate (ORR) was 31.8%, including 22.8%, 4.6%, and 4.6% achieving CR/CR with incomplete hematologicrecovery (CRi), partial response (PR), and the morphologic leukemia-free state (MLFS), respectively....In 6 efficacy-evaluable patients with newly diagnosed (ND) AML/MPAL, the ORR was 83.3%, with CR/CRi and PR achieved by 33.3% and 50% of patients, respectively. In 44 efficacy-evaluable patients with R/R AML/MPAL, the ORR was 43.2%, with CR/CRi, PR, and MLFS achieved by 31.8%, 4.5%, and 6.8% of patients, respectively. In 15 efficacy-evaluable patients with ND MDS/chronic myelomonocytic leukemia (CMML), the ORR was 80%, with CR and marrow CR (mCR) achieved by 40% and 40% of patients, respectively."

P1/2 data • Acute Myelogenous Leukemia • Chronic Myelomonocytic Leukemia • Myelodysplastic Syndrome

Phase 1b/2 Study of Lisaftoclax (APG-2575) Combined with Azacitidine (AZA) in Patients with Treatment-Naïve or Prior Venetoclax-Exposed Myeloid Malignancies (GlobeNewswire) - P1b/2 | N=24 | NCT04964518 | Sponsor: Ascentage Pharma Group Inc. | "Ascentage Pharma...announced that new clinical data...at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting....The combination of lisaftoclax and azacitidine was well tolerated, with initial signals of clinical activity. As of the data cutoff date of January 6, 2025, 97 patients were enrolled, with a median treatment duration of two cycles. In patients with TN-MDS/CMML, the overall response rate (ORR) was 64%, with complete response (CR) and marrow CR achieved by 29% and 36% of patients, respectively; in patients with R/R AML treated with lisaftoclax for 28 days or 14 days of repeated 28-day cycles, the ORRs were 39% and 50%, respectively, including CR rates of 28% and 37.5%, respectively; in patients with diseases refractory to venetoclax, the ORR was 17% in patients with AML/MPAL and 50% in patients with HR-MDS."

P1/2 data • Acute Myelogenous Leukemia

SYNERGISTIC EFFECTS OF OLVEREMBATINIB (HQP1351) COMBINED WITH BCL-2 INHIBITOR LISAFTOCLAX (APG-2575) AND BCL-2/BCL-XL INHIBITOR PELCITOCLAX (APG-1252) IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (T-ALL) (EHA 2025) - "Molecular mechanisms of action were assessed by western blotting.In both T-ALL cell lines, olverembatinib in combination with lisaftoclax or APG-1244 exhibited synergistic antiproliferative effects compared with single agents. Olverembatinib in combination with lisaftoclax and/or pelcitoclax demonstrated synergistic antitumor effects in T-ALL, providing a scientific rationale for further clinical evaluation of this novel combination therapy in patients with this condition."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ANXA5 • BCL2L1 • CASP3 • MCL1 • MYC

Effects of olverembatinib (HQP1351) in combination with BCL-2 inhibitor lisaftoclax (APG-2575) in T-cell acute lymphoblastic leukemia (T‑ALL) (AACR 2025) - "Olverembatinib in combination with lisaftoclax demonstrated synergistic antitumor effects in T-ALL, providing a scientific rationale for further clinical evaluation of this novel combination therapy in patients with T-ALL."

Combination therapy • IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2L1 • CASP3 • MCL1 • MYC

Effects of olverembatinib (HQP1351) in combination with Bcl-2 inhibitor lisaftoclax (APG-2575) in T-cell acute lymphoblastic leukemia (T-ALL) (GlobeNewswire) - "Olverembatinib in combination with lisaftoclax synergistically inhibited proliferation and augmented apoptosis in T-ALL cells in vitro. The combination synergistically suppressed tumor growth in a MOLT4 xenograft model in vivo. Mechanistically, olverembatinib inhibited Lck phosphorylation, and when combined with lisaftoclax, synergistically reduced downstream NF-kB p65 and BCL-xL, which is typically upregulated in T-ALL. The combination also downregulated phosphorylation of AKT and GSK3b kinases, resulting in degradation of MCL-1 and c-MYC, an essential pro-oncogenic protein in T-ALL."

Preclinical • T Acute Lymphoblastic Leukemia

Olverembatinib (HQP1351) in combination with lisaftoclax (APG-2575) overcomes venetoclax resistance in preclinical models of acute myeloid leukemia (AML) (AACR 2025) - "In summary, olverembatinib in combination with lisaftoclax successfully overcame venetoclax resistance in preclinical AML models by downregulating key signaling pathways shown to mediate such resistance. Overall, these findings suggest a potential new therapeutic strategy for venetoclax-resistant AML."

Combination therapy • IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CASP3 • FGFR • FLT3 • MCL1

ASCENTAGE PHARMA ANNOUNCES INCLUSION OF LISAFTOCLAX AND OLVEREMBATINIB IN CHINESE SOCIETY OF CLINICAL ONCOLOGY (CSCO) 2025 GUIDELINES (HKEXnews) - "Ascentage Pharma Group International...is pleased to announce that two of its proprietary novel drugs have been included in the 2025 Chinese Society of Clinical Oncology (CSCO) Guidelines. Lisaftoclax (APG-2575), the Company’s investigational novel oral Bcl-2 selective inhibitor, received its first recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Lymphoid Malignancies. Olverembatinib, the Company’s novel next-generation tyrosine kinase inhibitor (TKI), received an upgraded recommendation in the CSCO Guidelines for the Diagnosis and Treatment of Leukemias in Children and Adolescent, and retained its recommendations in the CSCO Guidelines for the Diagnosis and Treatment of Hematological Malignancies."

Clinical guideline • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Small Lymphocytic Lymphoma

Olverembatinib (HQP1351) in combination with lisaftoclax (APG-2575) overcomes venetoclax resistance in preclinical models of acute myeloid leukemia (AML) (GlobeNewswire) - "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 synergistically suppressed tumor growth in a MOLM-13-VEN-R AML xenograft model in vivo. 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."

Preclinical • Acute Myelogenous Leukemia

Ascentage Pharma To Present Data from Two Clinical Studies at 2025 ASCO Annual Meeting, Including Oral Presentation on Its Key Assets Lisaftoclax and Alrizomadlin (GlobeNewswire) - "Ascentage Pharma...announced that results from two clinical studies of the Bcl-2 selective inhibitor lisaftoclax (APG-2575) and the MDM2-p53 inhibitor alrizomadlin (APG-115), two key drug candidates in the company’s apoptosis-targeted pipeline, have been selected for presentations at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. These presentations will include an oral report featuring updated results from a Phase Ib/II study of a lisaftoclax combination regimen in patients with myeloid malignancies."

Clinical data • Acute Myelogenous Leukemia • Adenoid Cystic Carcinoma • Myelodysplastic Syndrome

Study of APG-2575 as a Single Agent or in Combination With Other Therapeutic Agents for CLL/SLL (clinicaltrials.gov) - P1 | N=144 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | N=35 ➔ 144 | Trial completion date: Jun 2026 ➔ Jun 2027 | Trial primary completion date: Mar 2025 ➔ Oct 2025

Enrollment change • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Key Business and Pipeline Updates (GlobeNewswire) - "Lisaftoclax (APG-2575)...We plan to seek clearance from the FDA to initiate a registrational Phase III clinical trial for the treatment of patients who are newly diagnosed with HR MDS."

New P3 trial • Myelodysplastic Syndrome

Ascentage Pharma to Present Five Preclinical Studies from Innovative Pipeline at American Association of Cancer Research (AACR) Annual Meeting 2025 (GlobeNewswire) - "Ascentage Pharma...announced that five abstracts highlighting the latest preclinical results from its pipeline programs have been selected for presentations at the 2025 American Association of Cancer Research Annual Meeting (AACR)....The data to be presented encompasses five of the company’s novel drug candidates: BCR-ABL tyrosine kinase inhibitor olverembatinib (HQP1351), Bcl-2 inhibitor lisaftoclax (APG-2575), FAK/ALK/ROS1 tyrosine kinase inhibitor APG-2449, EED inhibitor APG-5918, and IAP antagonist AS03157."

Preclinical • Acute Myelogenous Leukemia • Prostate Cancer • Small Cell Lung Cancer • T Acute Lymphoblastic Leukemia

Innovent to Present Preclinical Data of Multiple Novel Molecules at the 2025 AACR Annual Meeting (PRNewswire) - "Innovent Biologics...announces that preclinical data on multiple novel bispecific antibodies as well as antibody-drug-conjugates (ADCs) from its oncology pipeline will be presented at the American Association for Cancer Research (AACR) Annual Meeting 2025."

Preclinical • Acute Myelogenous Leukemia • T Acute Lymphoblastic Leukemia

The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy. (PubMed, Signal Transduct Target Ther) - "The first BCL2-selective BH3-mimetic, venetoclax, showed remarkable efficacy with manageable toxicities and has transformed the treatment of several hematologic malignancies. Following its success, several chemically similar BCL2 inhibitors such as sonrotoclax and lisaftoclax are currently under clinical evaluation, alone and in combination...Tumor-specific BCL-XL or MCL1 inhibition may be achieved by novel targeting approaches using PROTACs or selective drug delivery strategies and would be transformational in many subtypes of malignancy. Taken together, we envision that the targeting of BCL2 proteins, while already a success story of translational research, may in the foreseeable future have broader clinical applicability and improve the treatment of multiple diseases."

IO biomarker • Journal • Review • B Cell Lymphoma • Hematological Disorders • Lymphoma • Oncology • Targeted Protein Degradation • Thrombocytopenia • BCL2 • BCL2L1

Lisaftoclax (APG-2575) Combined With Azacytidine (AZA) in the Treatment of Patients With Higher-risk Myelodysplastic Syndrome (GLORA-4). (clinicaltrials.gov) - P3 | N=464 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Not yet recruiting ➔ Recruiting | Initiation date: Oct 2024 ➔ Jan 2025

Enrollment open • Trial initiation date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

…blockbuster new drugs expected to be approved for marketing in China in 2025 [Google translation] (Sohu.com) - "Ascentage Pharmaceuticals' lisaftoclax: This is a Bcl-2 selective inhibitor used to treat refractory or relapsed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). The drug's marketing application has been accepted by the CDE and is expected to be approved in 2025."

China approval • Chronic Lymphocytic Leukemia • Small Lymphocytic Lymphoma

Lisaftoclax (APG-2575) Combined with Novel Therapeutic Regimens in Patients (pts) with Relapsed or Refractory Multiple Myeloma (R/R MM) or Immunoglobulin Light‑Chain (AL) Amyloidosis (ASH 2024) - P1/2 | "This study evaluated the safety and efficacy of lisaftoclax combined with pomalidomide and dexamethasone (Pd; Arm A) or daratumumab, lenalidomide, and dexamethasone (DRd; Arm B) in R/R MM and lisaftoclax combined with Pd in R/R AL amyloidosis (Arm C). These combination therapies demonstrated a favorable safety profile with no drug-drug interactions, particularly in hematologic side effects. ClinicalTrials.gov registration : NCT04942067; internal study identifier : APG2575MU101."

Clinical • Acute Kidney Injury • Amyloidosis • Anemia • Constipation • Endocrine Disorders • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukopenia • Metabolic Disorders • Multiple Myeloma • Musculoskeletal Pain • Nephrology • Neutropenia • Oncology • Renal Disease • Thrombocytopenia

Abbv-453: A Highly Potent and Selective Next Generation Small Molecule Inhibitor of BCL-2 (ASH 2024) - P1 | "ABBV-453 demonstrated superior growth inhibition of the RS4; 11 xenograft compared to both sonrotoclax or lisaftoclax at equivalent doses and schedule. ABBV-453 has the potential to be the best-in-class next-generation BCL-2 inhibitor and is actively being investigated in phase 1 clinical trials in relapsed or refractory (R/R) MM (ClinicalTrials.gov ID, NCT05308654) and R/R CLL/SLL (NCT06291220)."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • ANXA5 • BCL2 • BCL2L1 • BCL2L2 • CASP3 • CASP7 • MCL1

Olverembatinib (HQP1351) in Combination with Lisaftoclax Overcomes Venetoclax Resistance in Preclinical Model of Acute Myeloid Leukemia (AML) (ASH 2024) - "Introduction The combination of BCL-2 inhibitor venetoclax with hypomethylating agents (HMAs) or low-dose cytarabine is widely used in treatment of patients with newly diagnosed AML who are elderly or ineligible for intensive chemotherapy. This combination downregulated signaling pathways shown to mediate venetoclax resistance. These promising findings suggest that this strategy may provide a new therapeutic option for patients with venetoclax-resistant AML, an urgent unmet medical need."

Combination therapy • IO biomarker • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • CASP3 • FGFR • FLT3 • MCL1

Lisaftoclax (APG-2575) Demonstrates Activity and Safety When Given with Accelerated Ramp-up and then Combined with Acalabrutinib or Rituximab in Patients (pts) with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Including Those with Prior Exposure to Venetoclax (ASH 2024) - P1, P3 | "We continue to accrue pts with prior ven exposure to further evaluate this promising signal. A global registrational phase 3 study GLORA (NCT06104566) is recruiting."

Clinical • IO biomarker • Anemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • Thrombocytopenia • IGH • TP53

Lisaftoclax (APG-2575), a Novel BCL-2 Inhibitor, in Combination with Azacitidine in Treatment of Patients with Myelodysplastic Syndrome (MDS) (ASH 2024) - P1/2 | "Internal study identifier : APG2575AC101. Clinicaltrials.gov identifier : NCT04501120."

Clinical • Combination therapy • IO biomarker • Anemia • Febrile Neutropenia • Infectious Disease • Myelodysplastic Syndrome • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • ASXL1 • RUNX1 • TET2 • TP53

APG-2449, a Novel Focal Adhesion Kinase (FAK) Inhibitor, Exhibits Antileukemic Activity and Enhances Lisaftoclax (APG-2575)-Induced Apoptosis in Acute Myeloid Leukemia (AML) (ASH 2024) - "This novel combination showed antileukemic activity in both BCL-2 inhibitor-sensitive and -insensitive AML cells in vitro and in xenograft models. Overall, these promising results provide a novel approach in the clinical development of lisaftoclax for treatment of patients with AML."

IO biomarker • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Solid Tumor • ALK • ANXA5 • BCL2L1 • MCL1 • STAT3

Safety and Efficacy of Olverembatinib (HQP1351) Combined with Lisaftoclax (APG-2575) in Children and Adolescents with Relapsed/Refractory Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia (R/R Ph+ ALL): First Report from a Phase 1 Study (ASH 2024) - P1 | "Dexamethasone 6 mg/m2/day was administered orally QD from D15-42. This regimen resulted in promising CR rates without intensive chemotherapy or immunotherapy. The study is currently in the dose-expansion phase."

Clinical • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Anemia • CNS Disorders • Epilepsy • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • Thrombocytopenia • ABL1 • BCR