Ascentage Pharma Announces IND China Approval for Phase I Study of APG-5918 in Patients with Advanced Solid Tumors or Hematological Malignancies

SUZHOU, China and Rockville, Md., November 9, 2022 /PRNewswire/ — Ascentage Pharma (6855.HK), a global biopharmaceutical company committed to developing novel therapies for cancers, chronic hepatitis B (CHB) and age-related diseases, today announced that its novel embryonic ectoderm development (EED) inhibitor, APG-5918, has been approved by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) to enter a study phase I in patients with advanced solid tumors or hematological malignancies. Following the recent authorization of the study in the United States, this approval in China marks a new step in the company’s strategy of simultaneous clinical development in both countries. APG-5918 is the first domestically developed novel EED inhibitor entering clinical development in China.

Ascentage Pharma logo (PRNewsfoto/Ascentage Pharma)

This Multicenter, Open-Label, Phase I Dose Escalation and Dose Expansion Study is Designed to Evaluate the Safety, Pharmacokinetics and Efficacy of Orally Administered APG-5918 in Patients with Solid Tumors advanced or hematological malignancies. Teacher. Ruihua Xupresident and director of Sun Yat-sen University Cancer Center, will be the principal investigator of this study.

EZH2, which is highly expressed in multiple tumors in humans, has been shown to promote tumor development and progression, and targeted inhibition of EZH2 methyltransferase activity has already proven to be a mechanistic approach. effective for the treatment of cancer. However, the secondary mutation of EZH2 can lead to acquired drug resistances, while the EZH1 homolog also has methyltransferase (MTase) activity that could limit the effects of EZH2 inhibitors. Studies have shown that the proteins composing the PRC2 complex and the histone activities of EZH2 (MTase; HMTase) are highly dependent on the scaffolding and modulating effects of EED. Compounds with inhibitory effects on EED, a subunit of PRC2, can disrupt the protein-protein interaction between EED and EZH2, resulting in damaged PRC2 functions, H3K27me3-induced silencing of PRC2 expressions and blocking the triple methylation of H3K27.1 Therefore, allosteric targeting of EED has gained wide popularity in recent years as a promising approach to inhibit the replacement of inactivated PRC2.

Discovered and developed by Ascentage Pharma, APG-5918 is a potent, selective, orally active, small molecule EED inhibitor with high binding affinity. APG-5918 can regulate tumor epigenetics and tumor microenvironment, and therefore has broad therapeutic potential for the treatment of hematological malignancies, solid tumors and non-oncological conditions. APG-5918 can selectively bind to the H3K27me3 domain of the EED protein, resulting in conformational changes to the H3K27me3 binding pockets in the EED protein, which can then prevent the EED from interacting with the HMTase EZH2. Preliminary data showed that APG-5918 has in vitro antiproliferative activity in various tumor cell lines and antitumor activity in patient-derived xenograft (PDX)/cell line-derived xenograft (CDX) models of EZH1 mutant B-cell non-Hodgkin’s lymphoma, IN1-negative malignant rhabdoid tumor, BAP1 mutant mesothelioma and Prostate cancer.

dr. Yifan ZhaiChief Medical Officer of Ascentage Pharma, said, “This approval of the clinical study of APG-5918 in China came shortly after the study was authorized in the United States and therefore signals major progress in Ascentage Pharma’s efforts to simultaneously advance clinical programs in China and the United States, and also demonstrates our global innovation capabilities. We look forward to working closely with Professor Xu to advance the clinical development of APG-5918, which we hope will offer new therapeutics to patients in need. »

Reference

1. Erokhin M, Chetverina O, Győrffy B, Tatarskiy VV, Mogila V, Shtil AA, et al. Clinical correlations of the polycomb 2 repressive complex in different tumor types. Cancers 2021;13:3155.

About Ascentage Pharma

Ascentage Pharma (6855.HK) is a global biopharmaceutical company engaged in the development of new therapies for cancers, chronic hepatitis B and age-related diseases. On October 28, 2019Ascentage Pharma was listed on the main board of the Stock Exchange of Hong Kong Limited under stock code 6855.HK.

Ascentage Pharma is focused on developing therapies that inhibit protein-protein interactions to restore apoptosis or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2 inhibitors and dual Bcl-2/Bcl-xL inhibitors, as well as candidates targeting the 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 regulators of apoptosis. The company is conducting more than 40 phase 1/2 clinical trials in the United States, Australia, Europeand China. Ascentage Pharma has been designated for several major national R&D projects, including five major new drug projects, new drug incubator status, four innovative drug programs and one major project for the prevention and treatment of infectious diseases.

Olverembatinib, the Company’s lead drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML), has been granted Orphan Drug Designation (ODD) and Fast Track Designation (FTD) by the US FDA. A New Drug Application (NDA) for HQP1351 was submitted and subsequently granted Priority Review status and Breakthrough Treatment Designation (BTD) by the Center for Drug Evaluation (CDE) in China. To date, Ascentage Pharma has obtained a total of 12 SDGs from the US FDA for four of the company’s investigational drug candidates.

Leveraging its strong R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with many renowned biotech and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD and AstraZeneca. The company has assembled a talented team with global experience in the discovery and development of innovative drugs and is establishing its world-class commercial manufacturing and sales and marketing teams. One of Ascentage Pharma’s main objectives is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfill its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients.

Forward-looking statements

Forward-looking statements made in this article relate only to events or information as of the date the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to publicly update or revise 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 unforeseen events. You should read this article in its entirety and be aware that our actual future results or performance may differ materially from what we expect. In this article, statements or references to our intentions or those of any of our directors or our company are made as of the date of this article. Each of these intentions may change in light of future development.

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Denise W. Whigham