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    Home > Medical News > Latest Medical News > CD47/SIRP alpha finally went to the front of the stage Gilead, AbbVie became the main camp

    CD47/SIRP alpha finally went to the front of the stage Gilead, AbbVie became the main camp

    • Last Update: 2021-01-10
    • Source: Internet
    • Author: User
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    Go around, high-value projects will generally end up in the pocket of global head multinational pharmaceutical companies.
    2020, CD47/SIRP alpha heat presses three strengthening keys: First, on March 02, 2020, Gilead acquired Forty Seven for $4.9 billion and obtained CD4 7 Single Anti-Assets Magrolimab, Forty Seven, $1.94 billion, down $180 million, September 04, 2020 Obtained a global commercial interest in Tiantian BioCD47 mono-resistant lemzoparlimab outside Greater China; NCT03248479) data, the FDA granted magolimab breakthrough therapy eligibility, which means that if the ongoing NCT04313881 goes well, magrolimab's launch will be a nail in the coffin.
    CD47/SIRP alpha finally went to the front of the stage, to meet a new beginning, among the ranks of focus on the target, but from the current data, the target in addition to high-risk myeloid growth abnormal syndrome showed excellent response, non-Hodgkin lymphoma initial response is not high, solid tumor (such as non-small, stomach cancer, head and neck cancer) whether single drug or combination, tumor response is poor.
    this article will focus on cd47/SIRP alpha drug development key points, and first update the KEY data of CD47/SIRP alpha published on SITC 2020.
    CD47/SIRP alpha on HITC 2020 fresh data Hot spot one: lemzoparlimab did not find hemolyse anemia, treatment-related anemia 30% 1-30 mpk did not appear DLT, common treatment-related adverse reactions in anemia 30%, are 1-2 levels;
    insoluble anemia.
    ≥ 20 mpk, CD47 target RO is fully saturated.
    the safety advantages of differentiation in the field of water are initially apparent, but we need to continue to pay attention to the clinical response.
    hot spot 2: 3 cases of 3/4 adverse reactions, bililin elevation, blood cell reduction, anemia recruitment patients 20 cases, treatment plan and magolimab similar, it is worth noting that the treatment-related adverse reactions, 4 cases (20%) Biliumin increased, 3 cases of anemia (15%), of which 1 case of bilium increase, 1 case of plate reduction, 1 case of anemia a total of 3 cases of 3/4 adverse reactions, which are related to IBI188 itself, safety compared to magolimab did not see any advantage.
    one. CD47/SIRP alpha: CD47 high expression in hematopoietic stem cells and myelin cells, prevent macrophages from devouring CD47, also known as integrator-related proteins, is a kind of Ig protein, hematopoietic stem cells, myelin stem cells, ancestral cells are high expression CD47, CD47 by binding with macrophage surface subject SIRP alpha, can reduce the phagocytosis signal, thus avoiding cell removal! Studies have confirmed that CD47 is highly expressed in a variety of tumor cells, including myeloid leukemia, non-Hodgkin's lymphoma, and multiple myeloma.
    highly expressed CD47 combined with SIRP alpha to prevent macrophage phagocytosphagy removal, a classic immune escape mechanism.
    , blocking the CD47-SIRP alpha signaling path is able to avoid immune escape, relieve immunosuppression, activate macrophages, T-cells, and restore tumor cell killing capacity.
    this is the most basic mechanism of action of this kind of drug, this is a new type of mechanism of action drug, the development progress has been concerned.
    two. Dark times: Case deaths and red blood cell reduction make the prospects for the development of such drugs confusing, blocking the CD47-SIRP alpha signaling path, and monoantial or fusion proteins are two types of large molecule drugs developed, ALX oncology, Forty, Seven Tioma Therapeutics, and Trillium are pioneers.
    1. Ti-061 Clinical Phase 1 case death, early termination of 23 May 2017, CD47 monoanti-Ti-061 Phase 1 clinical trial started in the United Kingdom;
    (EudraCT number, 2016-004372-22)。
    2. Celgene Terminated CC-90002 Project Development In early October 2018, Celgene updated NCT02641002 recruitment status, AML and high-risk MDS patients, the benefits are unclear, termination of development.
    November 13, 2019, 2019 AHS Conference, Celgene released data on the project NCT02367196 clinical trials, CC-90002-ST-001 clinical trials recruited a total of 28 patients to evaluate CC-90002 Combined Lytosi monoanti Safety and responsiveness data in patients with relapsed non-Hodgkin's lymphoma, 1 CR, 2 PR, 3 SD, ORR 13%, combined therapy overall response was very low, safety, anemia and plateplate reduction were two notable adverse reactions, of which treatment-related 3/4 anemia was 4%.
    2017-2018 was the most uncertain year for CD47-SIRP alpha development, with poor clinical response and safety disclosed by the projects, and the termination of the Ti-061 and CC-90002 pioneer projects left THE CD47-SIRP alpha biomechanics in the dark.
    wednesday. Super 50% complete remission, bone marrow hyperplising abnormal syndrome ignites project New Hope At the end of 2019, magrolimab announces the progress of a heavy Phase 1 NCT03248479 clinical trial at the 2019 ASH Annual Meeting, magro Limab combined with azagsin showed high tumor relief in first-line treatment in AML and MDS patients, with CR/CRi over 50%, good safety and tolerance, as follows: tumor response rate, first-line AML CR/CRi 5 5%, first-line MDS CR/CRi 50% perfect drug regimen can control anemia, control blood cell reduction Red blood cell reduction is one of the most concerned adverse reactions, which is related to the mechanism of action of this class of drugs, is unavoidable, magrolimab By the first 1 mg/kg induced dose, the next 30 mg/kg maintenance dose to achieve the goal of controlling blood cell reduction, the test disclosure data can be seen that the continuous drug hemoglobin levels can be gradually restored, hemoglobin infusion dependence is also rapidly decreasing.
    from the clinical trial disclosure data, magrolimab in high-risk bone marrow growth abnormal syndrome patients are very positive response, adverse reactions can be controlled, which gives the project development new hope.
    Thursday. With a market of $1 billion to $2 billion, myelin progenitor abnormal syndrome will usher in the innovative targeted therapy magolimab bone marrow progenitor syndrome (myelodysplastic syndrome), a heterogeneic myelin clone disease originating from hematopoietic stem cells, characterized by abnormal myelin cell development, characterized by ineffective hematopoietic, resuscable blood cell reduction, and high-risk acute myeloid leukemia (AML) transformation.
    Epidemiology shows that in the United States, there are 15,000 new cases/year of bone marrow growth syndrome and 7,000 deaths per year, and 21,000 new cases/year of acute myeloid leukemia and 11,000 deaths/year.
    diseases have urgent and unseeded clinical needs.
    estimates that the market size of high-risk bone marrow growth syndrome is expected to be $1 billion to $2 billion.
    Friday. Domestic Xinda biological leader, BMS, Gilead, AbbVie is the main camp and so on all the dust settled, the opportunity will never be there again.
    In 2016, CD47 projects in a number of companies around the world advanced clinical, so far, POC or registered clinical data for multiple projects around the world are of great concern, summarized as follows: From the current early clinical response data: 1. Solid tumor early response is poor, want to talk to you, head and neck cancer and stomach cancer early response is about 20%.
    head and neck cancer indications, ALX148 combined with Pabli pearl monoanti, the overall response of 20%; 3. Variety expectations, the safety and effectiveness of the new generation CD47 single resistance data, worthy of attention varieties are lemzoparlimab, AO-176.
    among them, the preliminary safety data of the SITC 2020 data in November showed that 30% of treatment-related anaemia, no severe anemia, no hemolytic anemia, drug use is also different from first-in-class Magrolimab, but because the clinical response data are not disclosed, it is necessary to continue to pay attention to; 4. At the corporate level, Gilead and Xinda Bio are world-leading, both in the first-line treatment of bone marrow growth abnormal syndrome registered clinically.
    , Gilead launched a registered clinical trial NCT04313881 in September 2020 and is expected to end in April 2022;
    : CD47/SIRPa data published by SITC 2020
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