APG-5918 / Ascentage Pharma - LARVOL DELTA

EMBRYONIC ECTODERM DEVELOPMENT (EED) INHIBITOR APG-5918 EXHIBITS POTENT ANTITUMOR ACTIVITY AND SYNERGIZES WITH HISTONE DEACETYLASE INHIBITOR TUCIDINOSTAT IN PRECLINICAL T-CELL LYMPHOMA (TCL) MODELS (EHA 2025) - "A subcutaneous HuT102 cell line-derived xenograft (CDX) model was established to assess in vivo antitumor efficacy.APG-5918 exhibited potent antiproliferative activity in vitro, with IC50 values ranging from 0.1 to 7.2 μM, outperforming dual EZH1/2i valemetostat and EZH2i tazemetostat. APG-5918 exhibited potent antitumor activity alone and synergized with tucidinostat in preclinical TCL models. Mechanistically, it modulated PRC2 complex and induced apoptosis and cell cycle arrest. Combination with tucidinostat further enhanced these effects."

Epigenetic controller • Preclinical • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CASP3 • CDK6 • EZH2

Embryonic ectoderm development protein (EED) inhibitor APG-5918 exhibits potent antitumor activity and synergizes with androgen receptor (AR) inhibitor enzalutamide in preclinical prostate cancer (PCa) models (GlobeNewswire) - "APG-5918 demonstrated superior inhibitory effects on PCa cell proliferation in vitro. APG-5918 in combination with enzalutamide synergistically suppressed cell proliferation. APG-5918 induced dose-dependent cell cycle arrest in LNCaP and C4-2B cells. Combining enzalutamide with APG-5918 deepened G0/G1 cell cycle arrest. APG-5918 showed significant antitumor activity in human LNCaP and enzalutamide-resistant 22Rv1 xenograft models in castrated nude mice. Mechanistically, APG-5918 downregulated key on-target PD markers (e.g., H3K27me3, EED, EZH2, SUZ12) and AR pathway proteins. APG-5918 also suppressed oncogenic driver ERG, DNA methylation factors (UHRF1, DNMT1), and antiapoptotic protein MCL-1, and reduced pRb, CDK4, cyclin B1 and cyclin D1—crucial mediators of cell cycle regulation."

Preclinical • Prostate Cancer

EED inhibitor APG-5918 renders vulnerability to immunotherapy by rewiring sphingolipid metabolism via nSMase2-ceramide pathway in pancreatic cancer (AACR 2025) - "Taken together, our results demonstrate that the novel EED inhibitor APG-5918 can reshape the tumor immune microenvironment by activating the nSMase2-ceramide pathway, overcoming immunotherapy resistance in pancreatic cancer. This promising approach, combining EED inhibition with PD-1 blockade, will be further explored in translational and clinical studies."

IO biomarker • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • GLI2

Embryonic ectoderm development protein (EED) inhibitor APG-5918 exhibits potent antitumor activity and synergizes with androgen receptor (AR) inhibitor enzalutamide in preclinical prostate cancer (PCa) models (AACR 2025) - "APG-5918 appeared to be more potent than two EZH2 inhibitors (tazemetostat, PF-06821497) and EED inhibitor ORIC-944 under the same experimental condition. APG-5918 alone or in combination with enzalutamide exhibited antitumor activity in preclinical PCa models, supporting EED inhibition (± AR antagonists) as a therapeutic strategy for PCa."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CCND1 • CDK4 • DNMT1 • MCL1 • SUZ12 • UHRF1

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

Embryonic Ectoderm Development (EED) Inhibitor APG-5918 Demonstrates Robust Antitumor Activity in Preclinical Models of T-Cell Lymphomas (TCLs) (ASH 2024) - "The antiproliferative activity of APG-5918 was superior to that of dual EZH1/2 inhibitor valemetostat and EZH2-selective inhibitor tazemetostat under the same experimental conditions. Mechanistically, APG-5918 likely exerts its antitumor activity by modulating the PRC2 complex, leading to apoptosis induction and cell cycle arrest. These findings provide a strong scientific rationale for the future clinical development of APG-5918 for TCLs."

IO biomarker • Preclinical • Hematological Disorders • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • ANXA5 • BCL2L11 • CASP3 • CDK6 • EZH2

ASH 2024 | Results From Three Clinical Studies of Ascentage Pharma’s Bcl-2 Inhibitor Lisaftoclax Selected for Presentations, Including an Oral Report (PRNewswire) - "Ascentage Pharma...today announced that the latest results from three clinical studies of one of the company's key drug candidate, lisaftoclax (APG-2575), have been selected for presentations, including an Oral Report, at the 66th American Society of Hematology (ASH) Annual Meeting. This is the third consecutive year in which clinical results on lisaftoclax have been selected by the ASH Annual Meeting. In 2024, results from multiple clinical and preclinical studies on four of the company's investigational drug candidates...have been selected for presentations...At this year's ASH Annual Meeting, Ascentage Pharma will present an Oral Report featuring the latest results from a Phase I/II study of lisaftoclax in patients with relapsed/refractory multiple myeloma (R/R MM) or immunoglobulin light-chain (AL) amyloidosis. Furthermore, the latest data of lisaftoclax combinations in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and myelodysplastic..."

Clinical data • Preclinical • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Small Lymphocytic Lymphoma

EED inhibition renders vulnerability to immunotherapy by rewiring ceramide metabolism in pancreatic cancer (ESMO 2024) - "Our results indicate the promising roles of the novel EED inhibitor APG-5918 in reshaping the tumor immune microenvironment, mechanistically through upregulating nSMase2-ceramide pathway, and overcoming the immunotherapy resistance in pancreatic cancer. The new therapeutic strategy of EED inhibitor combining with PD-1 antibody will be tested in further translational and clinical studies."

IO biomarker • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • GLI2

EMBRYONIC ECTODERM DEVELOPMENT (EED) INHIBITOR APG-5918 IMPROVES CHRONIC KIDNEY DISEASE- (CKD)-INDUCED HEMOGLOBIN (HB) INSUFFICIENCY IN PRECLINICAL MODELS OF ANEMIA (EHA 2024) - "76-fold of the control group, respectively, which was pharmacologically superior to the effects observed withhydroxyurea at 33 µM (~6. APG-5918 treatment led to inhibition of H3K27me3 and induction of HbF and Hb mRNA and protein in CD34⁺HSCs. APG-5918 improved hematologic parameters and renal function in a CKD-induced anemia model, eitheras a single agent or in combination with EPO. Figure 1."

Preclinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Oncology • Renal Disease • CD34 • HBB

EHA 2024 | Results from Five Studies of Ascentage Pharma's Key Drug Candidates Selected for Presentations at 2024 European Hematology Association Hybrid Congress (PRNewswire) - "Ascentage Pharma...announced today that the latest results from five studies have been selected for Poster Presentations at the 2024 European Hematology Association Hybrid Congress (EHA 2024). These posters will feature olverembatinib (HQP1351), the first and only China-approved third-generation BCL-ABL1 inhibitor; investigational lisaftoclax (APG-2575), a Bcl-2 selective inhibitor; and investigational APG-5918, an EED selective inhibitor."

Clinical data • Preclinical • Acute Lymphocytic Leukemia • Anemia • Chronic Myeloid Leukemia • Multiple Myeloma

Embryonic ectoderm development (EED) inhibitor APG-5918 (EEDi-5273) and MDM2 inhibitor alrizomadlin (APG-115) synergistically inhibit tumor growth in preclinical models of prostate cancer (PCa) (AACR 2024) - "Mechanistically, this combination likely modulated pathways related to DNA methylation, cell cycle, and apoptosis. The findings provide a scientific rationale for future clinical development of APG-5918 and alrizomadlin for PCa patients."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CDK6 • CDKN1A • DNMT1 • MCL1 • UHRF1

AACR 2024 | Ascentage Pharma Presents Results from Three Studies at 2024 American Association of Cancer Research Annual Meeting (PRNewswire) - "In PCa preclinical models, the combination of APG-5918 and alrizomadlin synergistically inhibited cellular proliferation and induced cellular apoptosis. APG-5918 in combination with alrizomadlin synergistically enhanced antitumor activity in PCa xenograft models in vivo. Mechanistically, PD analysis revealed that APG-5918 downregulated the oncogenic DNA methylation factors (UHRF1, DNMT1) and histone methylation marker H3K27me3. Alrizomadlin markedly downregulated UHRF1 and DNMT1, and upregulated p53 and p21 expression. Combined treatment further enhanced downregulation of DNMT1, UHRF1, cell cycle pathway proteins (pRb, CDK6), antiapoptotic protein MCL-1, and synergistically increased cleavage of PARP-1, a marker of apoptosis."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

AACR 2024 | Ascentage Pharma to Present Three Preclinical Studies at 2024 American Association of Cancer Research Annual Meeting (PRNewswire) - "Abstract#: 3223:...Results from this preclinical study show that in preclinical models of PCa, targeting both EED and MDM2 can synergistically enhance antitumor activities by modulating pathways related to DNA methylation, cell cycle, and apoptosis. These findings provide a scientific rationale for the future clinical development of APG-5918 in combination with alrizomadlin for the treatment of PCa."

Preclinical • Prostate Cancer

Embryonic Ectoderm Development (EED) Inhibitor APG5918 Improves Chronic Kidney Disease- (CKD)-Induced Hemoglobin Insufficiency in Preclinical Models of Anemia (ASH 2023) - "76-fold of the control group, respectively, which was pharmacologically superior to effects observed with hydroxyurea at 33 µM (~6. APG-5918 also showed synergistic antianemia effects when combined with EPO. These findings support APG-5918 as a novel treatment option for CKD-induced anemia."

Preclinical • Anemia • Chronic Kidney Disease • Hematological Disorders • Infectious Disease • Nephrology • Oncology • Renal Disease • CD34 • HBB • SUZ12

A Study to Investigate the Safety, Pharmacokinetics and Efficacy of APG-5918 in Healthy Subjects or Anemic Patients (clinicaltrials.gov) - P1 | N=115 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Hematological Disorders

A Study to Investigate the Safety, Pharmacokinetics and Efficacy of APG-5918 in Healthy Subjects or Anemic Patients (clinicaltrials.gov) - P1 | N=115 | Not yet recruiting | Sponsor: Ascentage Pharma Group Inc.

New P1 trial • Anemia • Hematological Disorders

Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Ascentage Pharma Group Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CAST • SMARCB1

Ascentage Pharma Announces IND Approval in China for Phase I Study of APG-5918 in Patients with Advanced Solid Tumors or Hematologic Malignancies (PRNewswire) - "Ascentage Pharma...today announced that its novel inhibitor of the embryonic ectoderm development (EED) protein, APG-5918, has been approved by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) to enter a Phase I study in patients with advanced solid tumors or hematologic malignancies....This multicenter, open-label Phase I dose-escalation and dose-expansion study is designed to assess the safety, pharmacokinetics, and efficacy of orally administered APG-5918 in patients with advanced solid tumors or hematologic malignancies."

New P1 trial • Hematological Malignancies • Oncology • Solid Tumor

Ascentage Pharma Announces IND Approval in China for Phase I Study of APG-5918 in Patients with Advanced Solid Tumors or Hematologic Malignancies (PRNewswire-Asia) - "Ascentage Pharma...announced that its novel inhibitor of the embryonic ectoderm development (EED) protein, APG-5918, has been approved by the Center for Drug Evaluations (CDE) of China National Medical Products Administration (NMPA) to enter a Phase I study in patients with advanced solid tumors or hematologic malignancies....This multicenter, open-label Phase I dose-escalation and dose-expansion study is designed to assess the safety, pharmacokinetics, and efficacy of orally administered APG-5918 in patients with advanced solid tumors or hematologic malignancies."

New P1 trial • Hematological Malignancies • Oncology • Solid Tumor

Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas (clinicaltrials.gov) - P1 | N=90 | Not yet recruiting | Sponsor: Ascentage Pharma Group Inc. | Trial completion date: Oct 2024 ➔ Sep 2025

Trial completion date • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SMARCB1

Ascentage Pharma Announces IND Clearance by the US FDA for First-in-Human Study of Novel EED Inhibitor APG-5918 (PRNewswire) - "Ascentage Pharma...announced that its novel inhibitor of the embryonic ectoderm development (EED) protein, APG-5918, has been cleared by the US Food and Drug Administration (FDA) to enter a first-in-human (FIH) study that will assess the safety, pharmacokinetics, and preliminary efficacy of APG-5918 in patients with solid tumors or hematologic malignancies. This multicenter, open-label Phase I study is designed to assess the safety and tolerability, and determine the dose-limiting toxicity, maximum tolerated dose, and recommended Phase II dose (RP2D) of orally administered APG-5918."

IND • New P1 trial • Hematological Malignancies • Oncology

Study of Safety, Pharmacokinetic and Efficacy of APG-5918 in Advanced Solid Tumors or Lymphomas (clinicaltrials.gov) - P1 | N=84 | Not yet recruiting | Sponsor: Ascentage Pharma Group Inc.

New P1 trial • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • Lung Cancer • Lymphoma • Mesothelioma • Nasopharyngeal Carcinoma • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • SMARCB1

Preclinical development of embryonic ectoderm development (EED) inhibitor APG-5918/EEDi-5273 for cancer therapy (AACR 2022) - "With regulatory approval of EZH2 inhibitor tazemetostat, a potentially effective successful cancer therapeutic strategy is now available for patients with epitheloid sarcoma and relapsed or refractory follicular lymphoma. In a mouse xenograft model derived from EZH2mut KARPAS-422 DLBCL cells, single-agent APG-5918 conferred potent and dose-dependent antitumor activity, resulting in durable complete tumor regression that correlated with inhibition of H3K27me3, induction of PRC2 target genes, and drug exposure in tumors. In summary, our results provide scientific rationale for the clinical development of APG-5918/EEDi-5273 in EZH2mut lymphomas and, potentially, other hematologic malignancies and solid tumors."

Preclinical • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Solid Tumor • EZH2 • SUZ12

AACR 2022 | Ascentage Pharma Presents Latest Results from Six Preclinical Studies at AACR Annual Meeting 2022 (PRNewswire) - "Ascentage Pharma...announced that it has presented the latest results from six preclinical studies of the company's five investigational drug candidates...at the 2022 American Association for Cancer Research (AACR) Annual Meeting....The preclinical study suggests that APG-2449 combined with CDK4/6 inhibitors may have therapeutic potential in mesothelioma and may warrant future clinical development....APG-5918 showed definitive in vitro and in vivo target engagement and on-target antitumor activity. APG-5918 demonstrated strong PD/PK correlation in mice bearing KARPAS-422 xenograft tumors....Our data provide the preclinical evidence for clinical development of APG-1842 in patients with KRASG12C-mutant solid tumors."

Preclinical • Lung Cancer • Mesothelioma • Oncology • Solid Tumor • Thoracic Cancer

Ascentage Pharma to Present Latest Results from Six Preclinical Studies at AACR Annual Meeting 2022 (PRNewswire) - "Ascentage Pharma...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."

Preclinical • Hematological Malignancies • Lung Cancer • Mesothelioma • Multiple Myeloma • Oncology • Solid Tumor • Thoracic Cancer