Menarini targets drug tagraxofusp by acquisition of layout CD123

Italian drugmaker Menarini Group has announced the acquisition of Stemline Therapeuticsfor aof up to $677m and acquired the drug Elzonris, which targets CD123CD123 is expressed in BPDCN and many other hematologic malignanciesElzonris is a CD123-oriented cytotoxin designed specifically for CD123 targets, which is a recombination of human IL-3 and cut-off diphtheria toxin (DT), in which the IL-3 domain directs cytotoxic DT fragments to tumor cells expressing CD123After internalizing tumor cells, Elzonris is able to irreversibly inhibit protein synthesis and induce apoptosis of target cellsElzonris was approved by the U.SFDA in December 2018 for the treatment of adult and pediatric patients with plasma cell-like dendritic cell tumors (BPDCN) aged 2 or older,is the first approved CD123 targeted drugElzonris (Picture: medscape)January 2019, Stemline submitted Elzonris' Marketing License Application (MAA) to the EMA for the treatment of BPDCN andwas granted an accelerated assessment by the EMA, which is expected to be decidedin the second half of this year, Stemline is evaluating other elzonris indications in clinical trials, including chronic granulocytic monocyaemia (CMML), myeloma fibrosis (MF), and acute myeloid leukemia (AML),and show early safety and efficacy CD123 Target introduction CD123 is a sub-
of the iso-isomer interleuke interleukin-3 receptor (IL-3R), which is widely expressed in human hematologic malignancies, including acute myeloid leukemia AML In addition, CD123 is also found in B-cell acute lymphoblastic leukemia (B-ALL), hair cell leukemia, plasma cell-like dendritic cell tumor (BPDCN), chronic granulocytic leukemia (CML) and Hodgkin's lymphoma At the same time, CD123 is normal cell low expression, so CD123 gradually become an attractive target for malignant tumors photo source: bpdcninfo although CD123 is low in normal tissue expression, but in some epithelial cells and mononucleosomes have low levels of expression, which makes double-resistant, CAR-T and other high-lethal therapies such as thin ice In fact, there are not many companies that lay out CD123-targeted drugs, including big pharmaceutical companies such as Novartis and Johnson and Johnson but sadly, Novartis invested heavily in Xencor's CD123/CD3 dual-specific antibody XmAb14045, which was suspended by the FDA in February 2019; A study of three pairs of specific antibodies JNJ63709178 was also suspended by the FDA in 2016; , CD123 is still in an awkward state, despite the limited number of tumor-specific antigens, especially solid tumors In this context, in addition to Stemline, a number of companies/institutions are developing CD123 targeted therapies, including Mustang Bio and City of Hope, Aptevo Therapeutics, etc See report: treatment of acute myeloid leukemia or new members: MB-102 (
CD123 CAR T) approved by the FDA Orphan Drug CD123 Targeting Therapy progress
July 24, 2019, Mustang Bio announced that the FDA awarded MB-102 (CD123 CAR-T) to treat acute myeloid leukemia (AML) orphan drug designation The FDA also previously awarded THE MB-102 (CD123 CAR-T) Orphan Drug designation for the treatment of cytoplasm-like dendritic cell tumors (BPDCN) MB-102 evaluated the safety and anti-tumor activity of Phase 1 dose-incremental clinical trials, and evaluated the efficacy of patients with an upgraded dose of MB-102 in relapsed or refractive AML (group 1) and BPDCN (group 2) MB-102 showed a complete response in low-dose acute myeloid leukemia and BPDCN without dose-limiting toxicity Aptevo Therapeutics, which owns APVO436, a dual-specific antibody candidate for CD123 and CD3, presented preclinical data on APVO436 at the 2019 American Cancer Research Association (AACR) annual meeting data show that APVO436 induces the production of functional memory T cells with primitive T-cell solute cell action, has good tolerance, antibody distribution between cells and volume distribution parameters, and extends serum half-life by 4.5 days in related non-clinical species It was also proved that APVO436 targeted CD123-positive tumor cells, induced the activation and proliferation of the original CD4 and CD8 T cells, but the cytokine activation level was lower compared with the version of anti-CD123 x anti-CD3 dual-specific molecules APVO436 is currently undergoing clinical trials in patients with AML and bone marrow hyperplasia syndrome (MDS) to assess the safety, pharmacokinetics and clinical activity of APVO436 , Ludaopei Hospital announced in 2018 that the first case of myeloid leukemia treated with CD123 CAR-T has been completely remissioned The patient had previously undergone 6 courses of chemotherapy and tested positive for the MLL-PTD gene mutation, the FLT3 ITD gene mutation, and up to 81% of peripheral hematogen cell cells during chemotherapy after receiving CD123 CAR-T cell retransmission, the patient had a fever for 5 days and sustained high fever for 2 days without a severe cytokine storm After 15 days of CAR-T cell redelivery, the bone marrow form is completely relieved and the small bone marrow residue reaches 0 concluded as Cowen analyst Boris Peaker said, if Menarini's layout of CD123 is successful, approved in Europe, and then pushed it globally, then there will be no less developers, and in this context, CD123 may be a chance! The future, let's wait and see! Network Source: Network