Ischemic stroke

March 12, 2024 -- Astrocyte Pharmaceuticals Inc., a clinical-stage biopharmaceutical company committed to advancing cerebroprotective therapies for individuals suffering from stroke, traumatic brain injury (TBI), and concussion, has announced today the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for its lead program, AST-004, for acute ischemic stroke. The company is preparing to initiate a Phase 2 clinical trial. The IND application clearance also paves the way for additional studies further exploring AST-004 in stroke, as well as TBI, and concussion. Currently, only ~5% of stroke patients receive pharmaceutical therapy, largely due to the short treatment windows of available thrombolytic medicines, as well as their need for imaging before those treatments can be initiated. AST-004 was developed with the potential to treat all stroke patients. Unlike existing therapies, treatment with AST-004 is designed for use without the need for imaging in the emergency room and for use at any point after diagnosis. And it has the potential to treat stroke occurring in any sized blood vessel in the brain. The upcoming Phase 2 trial in acute ischemic stroke patients builds upon the recent successful stroke clinical trial designs used by medical device companies, heralding a new era in patient care. “The past decade has witnessed a transformative shift in stroke trials, thanks to sophisticated imaging techniques that enable high-quality real-time characterization of stroke and ensure selection of homogeneous study groups,” said Dr. Kevin Sheth, Co-Director of the Center for Brain & Mind Health at the Yale School of Medicine and Chief Medical Advisor to Astrocyte. “The new study of AST-004 will first focus on treating those stroke patients with large vessel occlusions, offering hope to significantly diminish brain damage.” AST-004 is an innovative small molecule therapy that has demonstrated exceptional promise in preclinical studies. In a critical non-human primate stroke model, a significant reduction in brain lesion growth by 64% and an overall lesion size decrease by 45% were observed with a high dose (as reported in 'The Journal Stroke' in 2022). Astrocyte previously completed two Phase 1 safety trials in Europe, involving 80 participants in total, and saw no significant adverse effects or safety concerns. Dr. William Korinek, CEO of Astrocyte Pharmaceuticals, commented, “Since our founding in 2014, we have been focused on demonstrating the potential of cerebroprotective benefits of AST-004. Our robust preclinical program and Phase 1 studies have laid the foundation for our ongoing development efforts, and we are eager to move forward with the planned Phase 2 study. Stroke is the second leading cause of death globally, and the need for advances in treatment is enormous. We believe AST-004 can be part of that solution.” Astrocyte Pharmaceuticals Inc. is a privately held, clinical-stage drug discovery and development company dedicated to accelerating the recovery and well-being of brain injury patients. The company is committed to proving the cerebroprotective benefits of enhancing astrocyte function and advancing breakthrough therapeutic agents for treating brain injury resulting from stroke, traumatic brain injury, concussion, and neurodegenerative disorders such as Alzheimer’s disease. For more information on Astrocyte Pharmaceuticals Inc. and the AST-004 program, please visit us at Astrocyte Pharmaceuticals Inc. The content above comes from the network. if any infringement, please contact us to modify.

GROTON, Conn., March 12, 2024 (GLOBE NEWSWIRE) -- Astrocyte Pharmaceuticals Inc., a clinical-stage biopharmaceutical company committed to advancing cerebroprotective therapies for individuals suffering from stroke, traumatic brain injury (TBI), and concussion, has announced today the U.S. Food and Drug Administration (FDA) has cleared the company’s Investigational New Drug (IND) application for its lead program, AST-004, for acute ischemic stroke. The company is preparing to initiate a Phase 2 clinical trial. The IND application clearance also paves the way for additional studies further exploring AST-004 in stroke, as well as TBI, and concussion. Currently, only ~5% of stroke patients receive pharmaceutical therapy, largely due to the short treatment windows of available thrombolytic medicines, as well as their need for imaging before those treatments can be initiated. AST-004 was developed with the potential to treat all stroke patients. Unlike existing therapies, treatment with AST-004 is designed for use without the need for imaging in the emergency room and for use at any point after diagnosis. And it has the potential to treat stroke occurring in any sized blood vessel in the brain. The upcoming Phase 2 trial in acute ischemic stroke patients builds upon the recent successful stroke clinical trial designs used by medical device companies, heralding a new era in patient care. “The past decade has witnessed a transformative shift in stroke trials, thanks to sophisticated imaging techniques that enable high-quality real-time characterization of stroke and ensure selection of homogeneous study groups,” said Dr. Kevin Sheth, Co-Director of the Center for Brain & Mind Health at the Yale School of Medicine and Chief Medical Advisor to Astrocyte. “The new study of AST-004 will first focus on treating those stroke patients with large vessel occlusions, offering hope to significantly diminish brain damage.” AST-004 is an innovative small molecule therapy that has demonstrated exceptional promise in preclinical studies. In a critical non-human primate stroke model, a significant reduction in brain lesion growth by 64% and an overall lesion size decrease by 45% were observed with a high dose (as reported in 'The Journal Stroke' in 2022). Astrocyte previously completed two Phase 1 safety trials in Europe, involving 80 participants in total, and saw no significant adverse effects or safety concerns. Dr. William Korinek, CEO of Astrocyte Pharmaceuticals, commented, “Since our founding in 2014, we have been focused on demonstrating the potential of cerebroprotective benefits of AST-004. Our robust preclinical program and Phase 1 studies have laid the foundation for our ongoing development efforts, and we are eager to move forward with the planned Phase 2 study. Stroke is the second leading cause of death globally, and the need for advances in treatment is enormous. We believe AST-004 can be part of that solution.” About Astrocyte Pharmaceuticals Inc. Astrocyte Pharmaceuticals Inc. is a privately held, clinical-stage drug discovery and development company dedicated to accelerating the recovery and well-being of brain injury patients. The company is committed to proving the cerebroprotective benefits of enhancing astrocyte function and advancing breakthrough therapeutic agents for treating brain injury resulting from stroke, traumatic brain injury, concussion, and neurodegenerative disorders such as Alzheimer’s disease. For more information on Astrocyte Pharmaceuticals Inc. and the AST-004 program, please visit us at Astrocyte Pharmaceuticals Inc. Forward-Looking Statement This press release contains certain forward-looking statements regarding, among other things, statements relating to goals, plans, and projections regarding the company’s financial position, results of operations, market position, product development, and business strategy. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert, or change any of them and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed, and actual results may differ materially from such statements. The information in this release is provided only as of the date of this release, and the company undertakes no obligation to update any forward-looking statements contained in this release on account of new information, future events, or otherwise, except as required by law. Media contact: Kimberly Macleod – kim@kmacconnect.com info@astrocytepharma.com

Pictured: a conceptual drawing of the small extracellular vesicles, including exosomes/iStock, KS Kim Imagine a future where, instead of drugs that carry the risk of allergic responses and adverse events, materials made naturally by the human body can be used as medicine. A novel modality, exosomes might be on the cusp of making that future a reality, experts told BioSpace. Exosomes are membrane-bound sacs measuring tens of nanometers in diameter. They are produced by cells and may contain molecules such as RNA and enzymes to communicate with other cells. Since the 2010s, scientists have known that exosomes also have the potential to treat many conditions, particularly inflammatory ones. Over the past five years, investors have poured hundreds of millions of dollars into exosome-based therapeutics. Since 2018, the database clinicaltrials.gov has logged more than 100 trials involving exosomes, many of which are assessing therapeutics tailored to specific conditions like cancer. This boom has been fueled by incremental advances in research and a growing discontent with traditional cell therapies, which can be invasive, expensive and immunogenic, said Steven Stice, co-founder and CSO at Aruna Bio, which recently won FDA approval to begin clinical trials of its exosome, AB126. Exosomes appear to be compatible with the body and unlikely to be treated by the immune system as a foreign particle, potentially making them a safer alternative to cell therapy. But not everyone agrees. Are Exosomes Ready for the Clinic? Experts are divided on whether or not exosomes are ready to be used as therapeutics. Theresa Whiteside, a professor of immunology at the University of Pittsburgh who studies the use of exosomes as tumor biomarkers, does not believe exosome-based therapeutics are ready for clinical study. “We have no idea what regulates [exosome biology],” Whiteside told BioSpace. “At the moment, it's a confusing picture.” In the other camp, Sharanjot Saini, an associate professor in the department of biochemistry and molecular biology at Augusta University, is using exosomes to deliver drugs for neuroendocrine prostate cancer. Exosomes engineered by Saini’s lab to specifically deliver two drugs to the prostate “significantly” reduced tumor growth in mouse studies. Saini told BioSpace that if initial safety and toxicity tests are conducted with rigor, there is nothing standing in the way of using exosomes as therapeutics. Despite her objection to moving too quickly on the idea of exosome-based therapeutics, Whiteside does support their use as biomarkers. Studies from her lab show clear differences in the exosomes derived from healthy people and those from patients with tumors, and even in the exosomes from different types of cancer patients. Eventually, describing these exosomes in detail could help inform patients’ response to immunotherapy, Whiteside said. Key Players in the Exosome Space Several biopharma companies are working to develop exosome-based therapeutics for a wide array of conditions. The exosome diagnostics and therapeutics market is projected to grow by some $419 million during the five-year period ending in 2026, with North America accounting for 40% of that growth, according to a report published by Technavio. Aruna’s AB126 is the first exosome to enter human trials for a neurological indication. The company claims it can cross the blood-brain barrier and could help ischemic stroke patients by reducing inflammation in the brain, according to a press release, which notes plans to expand the asset into other neurological indications, including amyotrophic lateral sclerosis (ALS). Meanwhile, Rochester, Minnesota–headquartered RION in January began a Phase IIA trial for its purified exosome product, which is derived from platelets, for the management of diabetic foot ulcers. And in July 2023, Texas–based Direct Biologics announced promising results from a Phase II trial showing that its exosome, ExoFlo, reduced mortality in long COVID patients with acute respiratory distress syndrome. In parallel with the development of new therapies, firms are considering their manufacturing needs. In 2021, healthcare manufacturing giant Lonza acquired the exosome manufacturing facility of the now-defunct Codiak BioSciences. And contract development and manufacturing organizations (CDMOs) like RoosterBio have ramped up their services and partnered with other companies to address bottlenecks in exosome manufacturing. The trend is also taking off in Europe, where exosome-based therapeutics developer EXO Biologics launched a CDMO called ExoXpert to market their proprietary platforms as a service to other companies. Regulating Exosomes Because exosome-based therapeutics are so new, the FDA and other regulatory bodies such as the European Medical Agency (EMA) are working to draft relevant guidelines for their use. Eric Leire, CEO of Genflow Biosciences, which is using ExoXpert’s services to make mRNA-bearing exosomes, likened the current process to flying a plane and building it at the same time. CDMOs currently comply with current good manufacturing practices (cGMP), but the FDA has partnered with academic researchers to scrutinize the process and set quality control standards. Organizations like the International Society for Extracellular Vesicles (ISEV) are also filling this gap by periodically releasing recommendations for working with exosomes, the latest of which were published in 2023. These new guidelines not only outline best practices for isolation and purification but also clearly specify what can and cannot be called an exosome. When it comes to clinical trials, exosomes straddle two key regulatory areas: biologicals and cellular and gene therapy products (called advanced therapy medicinal products by the EMA). Walking that line and ensuring that any exosome-based products meet the safety and quality criteria in both fields is a stumbling block, EXO Biologics Chief Business Officer Romain de Rauville told BioSpace. He added that harmonization across different regulatory bodies should be made a priority to ensure exosome manufacturing and testing can be done smoothly across global sites. Tracey Worthington-Stice, co-founder and chief operating officer at Aruna Bio, stressed the importance of working closely with the FDA and beginning the process early. Doing so gave Aruna “a leg up,” she told BioSpace. The team also filed the Investigational New Drug Application and other regulatory forms themselves, which Stice noted gave them a clear understanding of the process. Manufacturing Exosomes at Scale Aruna Bio makes its exosomes in an in-house cGMP facility, which was “designed for flexibility,” Stice said. The adaptable nature of the facility allows the team to keep a close eye on the process and tweak the protocols when needed, which Stice said was critical for ramping up production and getting AB126 into clinic trials. Not all companies can afford in-house cGMP manufacturing, however. Finding people with the right expertise is also vital, Stice said. This is where CDMOs like ExoXpert come in. When Genflow decided to pivot from an AAV-based gene therapy to exosomes, it partnered with ExoXpert to make mRNA- and cDNA-containing exosomes. ExoXpert’s team offered crucial manufacturing know-how that Genflow lacked, Leire said, helping the latter push through what would have been an expensive and prolonged affair. Particularly challenging has been matching the scales of the upstream process, including getting cells to make the right kind of exosome, with the scales of the downstream process, like purifying the exosomes and getting consistent batches, de Rauville said. But Saini noted that academic developments and concerted efforts by ISEV to streamline and standardize a previously disjointed field have made these processes easier. “I have seen that shift from 2015. I think now . . . there is a good idea of what to expect with each exosome isolation method.” Going forward, the objective will be to back up the promise of exosomes with meticulous trials, de Rauville said. For Stice, there is value in taking therapeutics forward despite existing knowledge gaps. “There's so many unmet needs and diseases such as stroke and ALS,” he noted. “We need solutions now.” Sruthi S. Balakrishnan is a freelance academic editor, science writer and fact-checker based in Santa Barbara, California. She can be reached at sruthisb@sciscriber.com.