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    Home > Active Ingredient News > Antitumor Therapy > Open the indications for solid tumors to explore the Bcl-2 inhibitor APG-2575 of Ascent Pharmaceuticals obtains clinical trial approval from the U.S. FDA

    Open the indications for solid tumors to explore the Bcl-2 inhibitor APG-2575 of Ascent Pharmaceuticals obtains clinical trial approval from the U.S. FDA

    • Last Update: 2021-06-30
    • Source: Internet
    • Author: User
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    Suzhou, China and Rockville, Maryland, USA, June 15, 2021-Ascent Pharmaceuticals (6855.
    HK), which is committed to the development of innovative drugs in the treatment of tumors, hepatitis B and aging-related diseases, announced that the company is in research The clinical trial application of the original innovative drug Bcl-2 inhibitor APG-2575 was approved by the U.
    S.
    Food and Drug Administration (FDA), and the study of single drug or combined with anticancer drugs for advanced ER+ breast cancer or solid tumors will be launched
    .

    The study is a global multi-center, open, phase Ib/II clinical study, which aims to evaluate the progress of APG-2575 monotherapy in patients with advanced solid tumors, or in combination with CDK4/6 inhibitor palbociclib after treatment with CDK4/6 inhibitors.
    Or the safety, tolerability, PK characteristics and preliminary efficacy of relapsed ER+/HER2-metastatic breast cancer patients
    .

    Breast cancer is one of the most common malignant tumors in women.
    About 75% of breast cancer patients are hormone receptor positive (HR+) breast cancer [1], mainly estrogen receptor positive (ER+), about 85 of this subtype % Is Bcl-2 overexpression [2]
    .

    Endocrine therapy is the cornerstone of the treatment of HR+/HER2- breast cancer in the early and metastatic stages
    .

    In the first-line treatment of metastatic ER+ breast cancer, CDK4/6 inhibitors (including palbociclib, ribociclib, and abemaciclib) combined with hormone therapy can prolong no progression by targeting the CCND1-CDK4/6-RB pathway compared with hormone therapy alone.
    Survival period (PFS) and final overall survival (OS) [3, 4]; in second-line treatment, PI3K inhibitors combined with fulvestrant and everolimus combined with endocrine therapy can target the PI3K-AKT-mTOR pathway Overcome the selection pressure of previous treatments [3]
    .

    However, the resistance of endocrine therapy and targeted therapy is difficult to avoid, and chemotherapy is ultimately required.
    Therefore, exploring other new targeted therapies to block existing mutation pathways and delay chemotherapy are clinical problems that urgently need to be resolved
    .

    APG-2575 is a new type of oral Bcl-2 selective small molecule inhibitor under research by Ascent Pharmaceuticals, which restores the programmed cell death mechanism (apoptosis) of tumor cells by selectively inhibiting Bcl-2 protein, thereby inducing tumor cell apoptosis , To achieve the purpose of treating tumors
    .

    APG-2575 is the first locally developed Bcl-2 selective inhibitor that has entered the clinical stage in China.
    It has obtained multiple phase Ib/II clinical trials licenses in China, the United States, Australia and Europe, and it is advancing simultaneously globally.
    Clinical development of a hematological tumor indication
    .

    As a single agent, APG-2575 has strong anti-tumor activity against Bcl-2 dependent tumor cells, and in combination with other anti-cancer drugs, it exhibits broader anti-tumor activity
    .

    Previously, the results of preclinical studies of APG-2575 combined with palbociclib showed that palbociclib induces cell senescence by inducing cell cycle arrest, while APG-2575 increases the expression of pro-apoptotic proteins such as BIM, down-regulates ER levels, and reduces phosphorylated Rb and cells.
    protein levels of cyclin D1 and E
    .

    Therefore, the combination of Bcl-2 inhibitors and CDK4/6 inhibitors can not only synergistically enhance the induction of cell cycle arrest, but also promote the apoptosis of ER+ breast cancer cells
    .

    Yifan Zhai, Chief Medical Officer of Ascent Pharmaceuticals, said: "APG-2575 is an important clinical development product in the company's apoptosis product pipeline.
    The acquisition of the FDA's clinical approval for solid tumor indications is another milestone in the clinical development of the drug
    .

    As the first locally developed Bcl-2 selective inhibitor to enter the clinical stage in China, APG-2575's single-drug and combination therapy have great therapeutic potential and advantages
    .

    We have previously observed positive curative effects and good tolerance in hematological tumor indications.
    We look forward to more exploration and discovery of APG-2575 in the field of solid tumor indications
    .

    We are accelerating the clinical development of this species at the global level, hoping to benefit patients in China and the world as soon as possible
    .

    "Reference 1.
    McDonald, ES, et al.
    , Clinical Diagnosis and Management of Breast Cancer.
    J Nucl Med, 2016.
    57 Suppl 1: p.
    9s-16s.
    2.
    Razavi, P.
    , et al.
    , The Genomic Landscape of Endocrine-Resistant Advanced Breast Cancers.
    Cancer Cell, 2018.
    34(3): p.
    427-438.
    e6.
    3.
    Rozeboom, B.
    , N.
    Dey, and P.
    De, ER+ metastatic breast cancer: past, present, and a prescription for an apoptosis-targeted future.
    Am J Cancer Res, 2019.
    9(12): p.
    2821-2831.
    4.
    Lynce, F.
    , AN Shajahan-Haq, and SM Swain, CDK4/6 inhibitors in breast cancer therapy: Current practice and future opportunities.
    Pharmacol Ther, 2018.
    191: p.
    65-73.
    Develop innovative drugs in the treatment fields of tumors, hepatitis B and aging-related diseases
    .

    October 28, 2019, Asia-sheng medicine in the Hong Kong Stock Exchange Main Board listing, stock code: 6855.
    HK
    .

    Ascent Pharmaceuticals has a self-constructed protein-protein interaction targeted drug design platform, and is at the forefront of new drug development in the apoptosis pathway in the world
    .

    The company has established a pipeline of 8 new class 1 small molecule drug products that have entered the clinical development stage, including inhibitors that inhibit key proteins in the apoptosis pathway such as Bcl-2, IAP, or MDM2-p53; Inhibitors of kinase mutants, etc.
    , are the only innovative company in the world that has clinically developed varieties in the field of key proteins in the apoptosis pathway
    .

    The company is currently conducting more than 40 phase I/II clinical trials in China, the United States, Australia and Europe
    .

    The core product HQP1351, which is used to treat drug-resistant chronic myeloid leukemia, has been submitted for new drug marketing applications in China and has been included in the priority review and breakthrough therapy varieties
    .

    This variety has also obtained the U.
    S.
    FDA's fast track review and orphan drug certification
    .

    Up to now, the company has 4 new drugs under development that have obtained 11 FDA orphan drug qualification certifications
    .

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    .

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