GPVI

Results from a phase 2b trial in myocardial infarction are expected at the end of next year. Acticor Biotech is discontinuing a phase 2/3 study of a blood thinner given alongside heart surgery based on the results of a futility analysis.The French company had been testing the drug, glenzocimab, as an adjunct to mechanical thrombectomy in patients who have suffered an acute ischemic stroke. More than 100 patients have been enrolled in the study to date, with the futility analysis conducted on data from the first 78 participants.“In the light of the information provided to the members of the Independent Monitoring Committee (IMC), and in accordance with the futility criteria defined in the protocol, the IMC recommends that the GREEN study be discontinued,” Acticor said in a Friday release.Glenzocimab, which is Acticor’s sole asset, is an antibody fragment that’s directed against platelet glycoprotein VI (GPVI). The protein is critical for blood clot formation but doesn’t affect the regulation of bleeding, making it an ideal target for safely inhibiting platelet clumps.Glenzocimab is undergoing or in line for a number of clinical trials in relation to strokes or heart attacks, but this isn’t the first time the drug has come up short. In April, glenzocimab failed to hit the primary endpoint of reducing the risk of severe disability or death in the wake of a stroke across a separate phase 2/3 study. Early hopes for glenzocimab were that it could cut the risk of uncontrolled bleeding that can be a side effect of widely prescribed blood thinners such as COX-1 inhibitor aspirin and P2Y12 antagonist Plavix. This theory was back up by a small first-in-human study of the drug in healthy volunteers that read out in 2019.Those hopes continued into January 2024, when a phase 1b/2a study showed a reduction in mortality and brain bleeding among stroke patients who received the drug.Results from a phase 2b trial in myocardial infarction, a term for a heart attack, are expected at the end of next year.

International scientific meeting convenes in Bangkok, Thailand, for the first time highlighting the important work of the Asian-Pacific scientific and clinical community BANGKOK, June 17, 2024 /PRNewswire/ -- Today, the International Society on Thrombosis and Haemostasis (ISTH) announces that all ISTH 2024 Congress (June 22-26, 2024) abstracts are available online, including late-breakthrough abstracts, to give a detailed glimpse into the posters, presentations and plenaries that will be presented at the Congress in Bangkok, Thailand. At the ISTH 2024 Congress, thousands of the world's leading experts on thrombosis, hemostasis and vascular biology will convene in Bangkok, Thailand, to present the most recent advances, exchange the latest science and discuss the newest clinical applications designed to improve patient care. This marks the Congress's return to the Asia-Pacific region for the first time since it was held in Kyoto, Japan, in 2011, and its debut in Bangkok. Through an extensive lineup of educational sessions, poster and oral communications, state-of-the-art lectures, medical industry exhibits and professional networking opportunities, the Congress promotes the latest scientific discourse and advancement in the field. The following late-breakthrough abstracts will be highlighted during the ISTH 2024 Congress: Evaluation of recombinant human prourokinase in the treatment of acute pulmonary embolism (ERUPTE): A randomized, single-blinded, multicenter, phase 2 trial, Zhi-Cheng Jing, Guangdong Provincial People's Hospital, China Efficacy and safety of Mim8 prophylaxis in adults and adolescents with hemophilia A with or without inhibitors: Phase 3, open-label, randomized, controlled FRONTIER2 study, Maria Elisa Mancuso, IRCCS Humanitas Research Hospital, Italy EMA601, a novel humanised fab inhibits platelet Glycoprotein VI with unprecedented potency and protects mice from arterial thrombosis and ischemic stroke, Stefano Navarro, University of Würzburg, Germany To see a full list of the late-breakthrough abstracts that will be presented throughout the Congress, continue reading below. Sunday, June 23, 2024 Safety, tolerability, and efficacy of mezagitamab (TAK-079) in chronic or persistent primary immune thrombocytopenia: Interim results from a phase 2, randomized, double-blind, placebo-controlled study by David Kuter, Massachusetts General Hospital, United States – Late Breakthrough Session 1.1, 9:30 a.m., Plenary Hall Engineering FVIII protein for enhancing expression and secretion profile to achieve normal level of FVIII in plasma utilizing noninvasive transcutaneous ultrasound mediated gene delivery by Ivan Krivega, SonoThera, United States - Late Breakthrough Session 1.2, 9:45 a.m., Plenary Hall Evaluation of recombinant human prourokinase in the treatment of acute pulmonary embolism (ERUPTE): A randomized, single-blinded, multicenter, phase 2 trial, by Zhi-Cheng Jing, Guangdong Provincial People's Hospital, China - Late Breakthrough Session 1.3, 10:00 a.m., Plenary Hall EMA601, a novel humanised fab inhibits platelet glycoprotein VI with unprecedented potency and protects mice from arterial thrombosis and ischemic stroke, by Stefano Navarro, University of Würzburg, Germany - Late Breakthrough Session 1.4, 10:15 a.m., Plenary Hall Efficacy and safety of Mim8 prophylaxis in adults and adolescents with hemophilia A with or without inhibitors: Phase 3, open-label, randomized, controlled FRONTIER2 study, by Maria Elisa Mancuso, IRCCS Humanitas Research Hospital, Italy - Late Breakthrough Session 1.5, 10:30 a.m., Plenary Hall Due to limited space, the ISTH 2024 Congress will not hold a press conference this year. For more information about the ISTH 2024 Congress, visit and for all other media needs, visit the virtual press room: A bout the International Society on Thrombosis and Haemostasis (ISTH) Founded in 1969, the ISTH is the leading worldwide not-for-profit organization dedicated to advancing the understanding, prevention, diagnosis, and treatment of conditions related to thrombosis and hemostasis. ISTH is an international medical-scientific professional membership organization with more than 7,000 clinicians, researchers, and educators working together to improve the lives of patients in more than 110 countries around the world. Among its highly regarded activities and initiatives are education and standardization programs, clinical and laboratory practice guidelines and guidance, research activities, meetings and congresses, peer-reviewed publications, expert committees, and World Thrombosis Day on 13 October. Visit ISTH online at . SOURCE International Society on Thrombosis and Haemostasis

In a comparative study, researchers describe how two notable pathogens -- Escherichia coli and Acinetobacter baumannii -- employ distinctly different tools to fend off antibiotic attack by two different drugs. Antimicrobial resistance is a story of constantly moving parts and players. With every new or tweaked antibiotic or antimicrobial drug, the targeted pathogens begin the evolutionary dance of acquiring resistance, prompting researchers to constantly develop workarounds or entirely new classes of medicine. Understanding the underlying mechanisms of acquired antimicrobial resistance is critical to the fight, a case of knowing one's enemy. In a new paper published March 2, 2024 in npj Antimicrobials and Resistance, part of the Nature Portfolio, researchers at Sanford Burnham Prebys, working with Roche Pharma Research and Early Development, describe how two notable pathogens -- Escherichia coli and Acinetobacter baumannii -- employ distinctly different tools to fend off antibiotic attack. "This work was conceived as a comparative study of the mechanisms and dynamics of resistance acquisition for two drugs and two bugs," said senior author Andrei L. Osterman, Ph.D., at Sanford Burnham Prebys. "Comparing mutational landscapes triggered by the same drug in two distinct bugs allows us to deduce both shared and unique evolutionary trajectories toward resistance. A comparison of two drugs in the same bug reveals shared and unique mechanistic features of fundamental and translational importance, from drug discovery to rational optimization of treatment regimens." Both pathogens studied are gram-negative bacteria with shared characteristics, but also notable differences. For the most part, E. coli is a bacterium routinely found in the guts of humans and animals, where it resides with no ill effect. Some strains, however, do cause harm, everything from mild gastroenterological distress to urinary tract infections, respiratory illness and pneumonia. Acinetobacter baumannii is more problematic, particularly in clinical settings where it can cause severe infections, some life-threatening. Both bacteria have developed resistance to most current antibiotic treatments. In their paper, Osterman and colleagues combined experimental evolution in a continuous culturing device (morbidostat) with whole genome sequencing of evolving cultures to track how E. coli and A. baumannii acquired drug resistance against a pair of antibiotics that inhibit DNA gyrase, an essential enzyme in bacteria. Inhibiting the enzyme disrupts DNA synthesis and, subsequently, causes the bacteria to die. One antibiotic -- ciprofloxacin -- has been in active clinical use since 1987; the other -- GP6 -- is experimental. The researchers found that pathogenic bacteria with acquired resistance to ciprofloxacin remained susceptible to effective antimicrobial treatment by GP6 drug. However, the opposite was not true: evolution of resistance to GP6 also triggered resistance to ciprofloxacin. These findings underscored that E. coli and A. baumannii employ shared and unique mechanisms to acquire resistance to these two types of drugs. "Bacteria acquire resistance as a result of random mutational events that happen in the DNA replication as uncorrected 'typos'," said Osterman. "These spontaneously emerge in a handful of drug-resistant variants/strains out of godzillions of neutral mutations) under selective pressure." (A godzillion is a descriptive term, not a precise unit of measurement. It refers to a number of enormous size. In this case a number ranging between 108 to 109 neutral mutations.) These harmful mutations may underlie several types of resistance mechanisms, including modifying the protein targets of a given drug, the ability of bacterial cells to expel compounds (drugs) before they cause harm (efflux) and special bacterial enzymes that inactivate active drug compounds. Osterman said the work advances progress toward developing "resistibility profiles" of established and novel antimicrobial drugs, which would help set forth "boundaries for possible combinational treatment, including clinically relevant multidrug resistant strains. Our acquired knowledge provides crucial guidelines for all these translational activities." The findings are not limited to E. coli and A. baumannii. They have potential to at least partially predict resistance drivers across other closely related species posing significant health risks, including Pseudomonas, Salmonella and Klebsiella spp. all difficult-to-treat bacterial pathogens linked to serious and sometimes deadly infections. Additional authors on the study include Semen A. Leyn, James E. Kent, Jaime E. Zlamal and Marinela L. Elane, all at Sanford Burnham Prebys; and Maarten Vercruysse, Rocha Pharma. The study was supported by F. Hoffmann-La Roche Ltd and the National Institute of Allergy and Infectious Diseases (grant 5R01AI167977). The study's DOI is 10.1038/s44259-024-00021-y