TLR-9 agonists are a novel approach to immune reactivation in patients with chronic HBV. By stimulating cellular TLRs we expect to be able to elicit an innate immune response that leads to the production of cellular proteins that target viral infections.
Our lead TLR-9 program, CYT-003, was in-licensed from Cytos Biotechnology Ltd., where it was evaluated clinically in allergic asthma. We are currently evaluating the utility of CYT-003 in HBV. If positive, we may be able to utilize the existing safety database to expedite development.作者: newchinabok 时间: 2015-10-30 08:21
CYT003 offers a differentiated approach for the treatment for asthma that acts upstream of most therapeutic agents currently in development.
It is a targeted therapy based on a biological carrier filled with an activating ligand (agonist) of Toll-like receptor 9 (TLR9), a key mediator of innate immunity. TLR9 is the receptor that detects the presence of microbial DNA and induces the immune system’s first line of defense against bacterial infection. The TLR9 agonist of CYT003 is a synthetically produced oligonucleotide containing non-methylated CpG motifs as found in bacterial DNA and belongs to the class of A-type CpGs.
Toll-like receptors are expressed in a subset of immune cells called antigen-presenting cells (APCs; e.g. dendritic cells, macrophages, B-cells). APCs are typically found in tissues in contact with the external environment (skin, lining of the nose, lungs, stomach and intestines) and serve as an important element of the immune defense. APCs, and in particular dendritic cells, communicate with T-cells to orchestrate the immune response when challenged by bacteria or viruses.
TLR9 is predominantly expressed in plasmacytoid dendritic cells (pDCs) and B-cells in humans. CYT003 is actively taken up by pDCs, activates TLR9, and induces the production of type 1 helper T cell (Th1) cytokine IFN-alpha and the co-stimulatory molecule ICOS-Ligand. CYT003-activated pDCs are then postulated to inhibit type 2 helper T (Th2) cells, which are critically involved in the development of allergic asthma.作者: zgct 时间: 2015-10-30 19:41
Arbutus Biopharma Announces Third Quarter 2015 Financial Results
VANCOUVER, British Columbia and DOYLESTOWN, Pa., Nov. 5, 2015 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq:ABUS), an industry-leading therapeutic solutions company focused on developing a cure for chronic hepatitis B virus infection (HBV), today announced its third quarter 2015 unaudited financial results and provided a corporate update.
"We are excited to advance the development of our lead HBV candidate, TKM-HBV, to a Phase II, multi-dosing, clinical trial that will measure hepatitis B surface antigen (HBsAg) reduction in HBV infected patients," said Dr. Mark J. Murray, Arbutus' President and CEO. "We are also accelerating the development of our other promising HBV candidates, in particular, those that target cccDNA formation and core protein/capsid assembly."
Recent Company Highlights
Arbutus announced progression of TKM-HBV to Phase II studies in HBV infected patients based on results from a Phase I single ascending dose study. The TKM-HBV product candidate that will be studied in Phase II will be referred to as ARB-1467.
Arbutus presented preclinical HBV data at the 2015 International Meeting on Molecular Biology of Hepatitis B Viruses, held on October 4-8, 2015. The presentations were titled: 1) "Profiling the Effects of TKM-HBV on cccDNA in Humanized Chimeric Mouse Model of HBV"; 2) "TKM-HBV, a Novel RNA Interference Treatment for Chronic Hepatitis B, Mediates Global Viral Antigen Reductions through a Well-Defined Mechanism of Action"; and 3) "Novel Inhibitors of HBV cccDNA Formation Exhibit Synergistic Effects with Nucleoside and Nucleotide Analog."
Arbutus announced plans to present at the 2015 American Association for the Study of Liver Diseases (AASLD) Liver Meeting held on November 13-17, 2015. The titles of Arbutus' accepted abstracts are: 1) "TKM-HBV, a Novel RNA Interference Treatment for Chronic Hepatitis B, Rapidly Reduces Surface Antigen and other Viral Proteins in Both Intrahepatic and Peripheral Compartments"; 2) "TKM-HBV, a Novel RNA Interference Treatment for Chronic Hepatitis B, has a Complementary Mode of Action to Current Standard of Care Nucleos(t)ide Analogs"; and 3) "Development of a Direct RNA Interference Therapy for Hepatitis Delta Virus Infection."
Upcoming Pipeline Milestones
4Q15: Initiate phase II, multi-dose efficacy study of TKM-HBV in chronically infected patients
2016: HBsAg reduction data from TKM-HBV Phase II trial (final data in 2H16)
2016: Initiate clinical immune biomarker study for CYT-003 in HBV chronically infected patients
2H16: File IND (or equivalent) for cccDNA formation inhibitor
2H16: File IND (or equivalent) for core protein/capsid assembly inhibitor
2017: Initiate combination studies including two or more Arbutus HBV product candidates作者: newchinabok 时间: 2015-11-9 21:43