Target CCR5 for triple negative breast cancer (TNBC)! Cytodyn new monoclonal antibody leonlimab applies for breakthrough drug qualification (BTD) in the United States!

January 16, 2020 news / BIOON / -- cytodyn is a late clinical biotechnology company focusing on the development of a new humanized CCR5 antagonist, leonlimab (pro140), for a variety of treatment indications Recently, the company announced that it has submitted a breakthrough drug qualification (BTD) application to the U.S Food and Drug Administration (FDA) to use leonlimab as an adjuvant treatment for metastatic triple negative breast cancer (mtnbc) The BTD application is based on data from the first patient in the company's mtnbc Ib / II phase study, and data from an additional single patient trial to evaluate leonlimab's treatment of HER2 + metastatic stage 4 breast cancer (MBC) according to an emergency investigational new drug (ind) protocol These data continue to show a very promising clinical response Data from the first mtnbc patient in the IB / II phase study showed that after 11 weeks of treatment with leonlimab, no circulating tumor cells (CTC) or presumptive metastatic tumor cells were detected in the peripheral blood, and the expression of CCR5 in cancer-related cells was further significantly reduced The patient's data also showed that after several weeks of treatment, the tumor shrank by more than 20% In the case of stage 4 MBC patients in the emergency ind program, cancer has been transferred to the liver, lung and brain This patient has been treated with Herceptin (Herceptin, trastuzumab, HER2 targeted mAb) and perjita (paltuzumab, HER2 targeted mAb) for more than 1.5 years During the three weeks of treatment with leonlimab, two MRI scans showed that the tumor continued to shrink significantly, the brain edema decreased, several metastatic tumors disappeared, and there was no new metastasis in the liver, lung and brain At the end of February 2019, cytodyn company published the results of leronlimab treatment MBC animal research: in the mouse xenotransplantation cancer model (used to simulate human breast cancer metastasis), the application of leronlimab for 6 weeks reduced the breast cancer metastasis rate by more than 98% Studies have shown that CCR5 inhibition may destroy signal transduction and ultimately the proliferation of CCR5 + circulating tumor cells (CTC) Bruce Patterson, partner of cytodyn and chief executive officer of single cell diagnostic company incell DX, said: "this powerful data confirms the effect of leonlimab as a CCR5 inhibitor on patients with mtnbc, and obviously replicates the results of early animal studies - leonlimab treatment eliminated 98% of cancer metastasis in the study animals Our group of key opinion leaders believes that all cancer patients with similar CCR5 expression may also benefit from leonlimab treatment, including melanoma, brain cancer, laryngeal cancer, lung cancer, gastric cancer, breast cancer, ovarian cancer, uterine cancer, pancreatic cancer, bladder cancer and thyroid cancer We also believe that the mechanism of action of leonlimab has the potential to be used in autoimmune diseases such as multiple sclerosis, polymyositis, Crohn's disease, inflammatory bowel disease and psoriasis " Breakthrough drug qualification (BTD) is a new drug review channel established by FDA in 2012 It aims to accelerate the development and review of new drugs for the treatment of serious or life threatening diseases and there is preliminary clinical evidence that the drug can substantially improve the condition compared with existing treatment drugs The drugs that obtain BTD can receive more close guidance, including FDA senior officials, during the research and development, so as to guarantee to provide patients with new treatment options in the shortest time In 2019, the FDA Center for drug evaluation and Research (CDER) approved 48 new drugs, 29 of which used at least one fast approval channel 13 of these drugs have been identified by BTD, accounting for 27% of the total number of new drugs approved in that year Leonlimab (pro140) is a humanized IgG4 monoclonal antibody, which can target and block chemokine receptor 5 (CCR5) It is a cell receptor, and plays a variety of roles in HIV infection, tumor metastasis and other immune-mediated diseases (including NASH): (1) treatment of HIV / AIDS: Leonlimab is a new type of therapy called viral entry inhibitors, which can mask CCR5 and protect these cells from virus infection by blocking the entry of major HIV (R5) subtypes into healthy T cells At the same time, leonlimab does not seem to interfere with the normal function of CCR5 in mediating immune response The data of 9 clinical studies that have been successfully completed in more than 800 people show that leonlimab can significantly reduce or control the HIV load of patients in each study A phase IIB study showed that the single drug treatment of leonlimab could prevent HIV escape, and some patients who received leonlimab treatment had virus inhibition for more than 4 years In the United States, the FDA has awarded leonlimab the fast track qualification for HIV infection treatment Cytodyn has successfully completed a critical phase III study of leronlimab in combination with standard antiretroviral therapy for HIV infected people who have previously received treatment, and is rolling in a biologics licensing application (BLA) for combination therapy to the US FDA The company is also conducting another phase III study using leonlimab as a weekly monotherapy for people living with HIV Compared with HIV drugs currently used, leonlimab seems to be a powerful antiviral drug with fewer potential side effects and lower administration frequency (2) Treatment of cancer: some studies have shown that CCR5 plays a central role in tumor invasion and metastasis In some cancers, increased CCR5 expression is an indicator of disease status Published studies have shown that blocking CCR5 can reduce tumor metastasis of invasive breast cancer and prostate cancer in laboratory and animal models In the mouse xenotransplantation model, leonlimab reduced more than 98% of human breast cancer cell metastasis Cytodyn is currently conducting a phase II human clinical trial of metastatic triple negative breast cancer (mtnbc) In May 2019, the U.S FDA awarded leronlimab the fast track qualification for the treatment of mTNBC The company is also conducting additional research on leonlimab in cancer and Nash, and plans to conduct additional clinical trials in due course (3) In terms of immune signal transduction, CCR5 receptor also plays a key role in modulating the transfer of immune cells to inflammatory sites, which is crucial for the development of acute graft-versus-host disease (aGVHD) and other inflammatory diseases Clinical studies have shown that blocking CCR5 with chemical inhibitors can reduce the clinical effect of aGVHD without significantly affecting the implantation of transplanted bone marrow stem cells At present, cytodyn company is carrying out a phase II clinical study of leonlimab, which further supports the view that CCR5 receptor on implanted cells is essential for the development of aGVHD, and blocking the receptor to recognize specific immune signal molecules is a feasible method to alleviate aGVHD In the United States, the FDA has granted leonlimab the orphan drug qualification to prevent GVHD (Note: for the important milestones in clinical development project, future prospect and treatment of HIV and cancer of leonlimab (pro140), click the investor presentation of cyclodyn company in January 2020 The original source: cyclodyn files for breakthrough therapy design with the FDA for the use of leonlimab for the treatment of metastatic triple negative Breast Cancer