Astrocyte Pharmaceuticals Receives NIH Award to Evaluate AST-004 in Substance Use Disorders

$400,000 program extends AST-004 into another major CNS indication and reinforces the breadth of its cerebroprotective potential

GROTON, Conn., Aug. 25, 2026 (GLOBE NEWSWIRE) -- Astrocyte Pharmaceuticals Inc., a clinical-stage biotechnology company developing first-in-class cerebroprotective therapies, the Oklahoma Medical Research Foundation (OMRF), and The University of Texas at San Antonio today announced the award of a Phase I Small Business Technology Transfer (STTR) grant of approximately $400,000 from the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), to evaluate Astrocyte’s lead drug candidate, AST-004, as a potential treatment for substance use disorders. The award will support a collaborative preclinical research program evaluating the effects of oral AST-004 in established rodent models of psychostimulant addiction.

The project, entitled "Preclinical efficacy of AST-004 as a treatment for substance use disorder," brings together Astrocyte Pharmaceuticals' expertise in astrocyte biology and translational drug development with the addiction neuroscience expertise of Michael Beckstead, Ph.D., Senior Scientist at OMRF and Principal Investigator of the NIH award, and Matthew Wanat, Ph.D., Associate Professor at UT San Antonio. The research will leverage complementary rodent models to evaluate the therapeutic potential of AST-004 in substance use disorders.

Substance use disorders remain one of the nation's most significant public health challenges. According to the 2023 National Survey on Drug Use and Health, approximately 48.5 million Americans aged 12 years and older met criteria for a substance use disorder during the previous year. Psychostimulant addiction, including cocaine and methamphetamine use disorders, contributes substantially to overdose mortality, healthcare utilization, lost productivity, and broader societal costs. Despite decades of research, there are currently no FDA-approved medications for such stimulant use disorders.

Over the past decade, neuroscientists have increasingly recognized astrocytes as central regulators of brain homeostasis rather than passive support cells. Astrocytes play essential roles in synaptic function, metabolic support, glutamate and ion homeostasis, neuroinflammation, blood-brain barrier integrity, and the brain's response to injury and stress. Astrocyte dysfunction has increasingly been implicated across neurological conditions including stroke, traumatic brain injury, neurodegenerative disease, and substance use disorders, creating new opportunities to develop therapies that enhance astrocyte function and the brain's intrinsic protective and repair mechanisms.

AST-004 was specifically designed to target this emerging biology. The proprietary small molecule enhances astrocyte mitochondrial energy production through activation of adenosine A1/A3 receptors preferentially expressed on astrocytes. Previous research has demonstrated significant efficacy across multiple animal models of ischemic stroke and traumatic brain injury, while growing evidence indicates that abused psychostimulants similarly impair astrocyte function and disrupt astrocyte-neuron interactions. The new program will test whether enhancing astrocyte energy metabolism with AST-004 can favorably modify behaviors associated with psychostimulant use and relapse.

The STTR project will evaluate whether oral AST-004 reduces cocaine and methamphetamine self-administration, drug seeking following abstinence, and relapse-like behaviors in complementary rat and mouse models while preserving normal reward-related and behavioral function. Successful completion of the project is expected to establish proof of concept supporting future clinical development of AST-004 for substance use disorders.

"Independent preliminary studies conducted at both OMRF and UT San Antonio suggest that AST-004 might reduce psychostimulant intake in animal models," said Michael Beckstead, Ph.D., Senior Scientist at OMRF and Principal Investigator of the NIH-funded project. "We now have the opportunity to rigorously test those findings across different laboratories, species, and experimental paradigms. If the reduced drug use is consistent and normal behaviors are maintained, it would support a fundamentally new approach to treating substance use disorders that we could then move toward clinical evaluation."

"This award builds on the tremendous momentum our company has achieved over the past year, including the successful completion of our Series B financing and continued advancement of our clinical development programs," said William Korinek, Ph.D., Chief Executive Officer of Astrocyte Pharmaceuticals. "We are building an increasingly broad body of evidence around AST-004, from our Phase 2 program in sports-related concussion, to planned clinical development in complicated mild TBI and acute ischemic stroke, and now promising research in substance use disorders. These are very different clinical conditions, yet each involves important aspects of astrocyte function and the brain's response to injury, disease, or stress. Seeing a common biological strategy emerge across such diverse settings is tremendously exciting and continues to expand our view of the therapeutic potential of AST-004."

AST-004 has successfully completed two Phase 1 clinical safety studies and is currently being evaluated in a Phase 2 clinical trial in sports-related concussion in Australia. Additional clinical programs are being advanced in complicated mild TBI and acute ischemic stroke, supported by a preclinical efficacy package spanning multiple models and species of traumatic and ischemic brain injury.

The NIH STTR program is designed to accelerate commercialization of promising biomedical discoveries by fostering collaborations between innovative small businesses and leading nonprofit research institutions. The new award builds on Astrocyte Pharmaceuticals' long-standing research partnership with UT San Antonio, where foundational studies of AST-004 and astrocyte biology have been conducted for more than a decade, while establishing a new collaboration with OMRF and its expertise in addiction neuroscience. The program brings these capabilities together to investigate a promising new therapeutic application for AST-004.

Together, the broadening preclinical and clinical research around AST-004 is highlighting astrocyte energy metabolism as a potentially critical, conserved pathway for maintaining brain health and responding to injury, disease, and neurological stress. The apparent relevance of this central mechanism across distinct neurological conditions is particularly exciting, creating the possibility for AST-004 to ultimately have therapeutic impact across multiple areas of substantial unmet clinical need.

About AST-004

AST-004 is Astrocyte Pharmaceuticals’ lead proprietary small molecule designed to enhance astrocyte mitochondrial energy production through activation of adenosine A1/A3 receptors. By increasing the energy available to astrocytes, AST-004 is intended to enhance intrinsic cerebroprotective and repair mechanisms that support the brain’s response to injury, disease, and neurological stress. AST-004 is currently in Phase 2 clinical development for sports-related concussion, with additional clinical programs being advanced in complicated mild traumatic brain injury and acute ischemic stroke, alongside preclinical research in additional neurological indications.

About Astrocyte Pharmaceuticals Inc.

Astrocyte Pharmaceuticals is a clinical-stage biotechnology company developing first-in-class cerebroprotective therapies that target astrocytes to enhance the brain’s intrinsic ability to protect and repair itself. The company is advancing AST-004 across multiple acute neurological conditions, supported by a growing body of clinical, translational, and preclinical research. For more information, visit www.astrocytepharma.com.

About Oklahoma Medical Research Foundation

The Oklahoma Medical Research Foundation is an independent, nonprofit biomedical research institute dedicated to understanding, treating and preventing human disease. OMRF scientists conduct research in neuroscience, autoimmune disease, aging, cardiovascular disease, cancer, genetics, and infectious disease.

For more information, visit www.omrf.org.

About The University of Texas at San Antonio

The University of Texas at San Antonio (UT San Antonio) is a premier public research university dedicated to excellence in education, research, discovery and commercialization, health, public service, and community engagement. With over 40,000 students and more than $500 million in annual research expenditures, UT San Antonio brings together broad expertise spanning biomedical science, health, engineering, artificial intelligence, cybersecurity, business, and the liberal arts. The university is committed to translating discovery into innovations that improve lives and strengthen communities.

For more information, visit www.utsa.edu.

NIH Funding Acknowledgment

Research described in this press release is supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R41DA064479. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Forward-Looking Statement

This press release contains forward-looking statements regarding, among other matters, the development, potential benefits, clinical and preclinical evaluation, and future development plans for AST-004. These statements are based on current expectations and are subject to risks and uncertainties that could cause actual results, development timelines, or outcomes to differ materially from those expressed or implied. Forward-looking statements are not guarantees of future performance. The information in this release is provided as of the date hereof, and Astrocyte Pharmaceuticals undertakes no obligation to update these statements except as required by applicable law.

Media contact:   info@astrocytepharma.com