AST-004 / Astrocyte Pharma - LARVOL DELTA

Adenosine A1/A3 receptor agonist AST‑004 enhances metabolic resilience and structural repair across astrocyte subpopulations, with therapeutic efficacy, target engagement, and injury‑defined biomarker responses in a human in vitro trauma platform (Neuroscience 2026) - "AST-004 also reduced trauma-induced GFAP proteolysis relevant to post-traumatic astrocyte proteinopathy (Wanner 2026). Together, these human astrocyte data demonstrate that broad nanomolar AST-004 concentration ranges bolster astrocyte mitochondrial bioenergetics, promote cellular repair following cell wounding, and attenuate AID biomarker release."

First-in-human • Preclinical • CNS Disorders • Proteinopathy • Vascular Neurology • GFAP

AST-004-2-03: Cosmos Trial: Cerebroprotection Of AST-004 in Mild Complicated Traumatic Brain Injuries (clinicaltrialsregister.eu) - P1/2 | N=48 | Not yet recruiting | Sponsor: Astrocyte Pharmaceuticals Inc.

New P1/2 trial • CNS Disorders • Vascular Neurology

The long march towards testing the adenosine receptor agonism hypothesis for human cerebroprotection: The story of the A1R/A3R receptor agonist AST-004. (PubMed, Purinergic Signal) - "Subsequent research demonstrated that astrocyte mitochondrial ATP production could be activated by AST-004, resulting in significant efficacy in rodent models of permanent and transient occlusion AIS, porcine models of TBI and a non-human primate model of AIS as well as models of neurodegeneration and addiction. The purpose of this review is to highlight the research that led to the discovery of AST-004, summarize its widespread preclinical efficacy in a variety of disease models, and describe how this compound's excellent safety and pharmaceutical profile is differentiated from prototypical A1R and A3R agonists formerly or currently in the clinic."

Journal • Review • Cardiovascular • CNS Disorders • Ischemic stroke • Psychiatry • Vascular Neurology

The Effects of Adenosine A1/A3 Receptors Agonist on Improving the Outcomes of TBI and Stroke: Focus on AST-004. (PubMed, Curr Neurol Neurosci Rep) - No abstract available

Journal • Review • Cardiovascular • CNS Disorders • Inflammation • Ischemic stroke • Vascular Neurology

First-in-Human Phase I Clinical Trial of the Adenosine A1R/A3R Agonist AST-004 in Healthy Subjects. (PubMed, Stroke) - "AST-004 was safe and well-tolerated at plasma concentrations 3 to 8× higher than those associated with significant efficacy in astrocyte's preclinical primate stroke efficacy studies, with CSF concentrations highest at the 60-minute collection timepoint, the last timepoint tested. This study supports additional clinical investigations, including evaluation of an extended infusion to support the phase 2 program in stroke and traumatic brain injury."

Journal • P1 data • Cardiovascular • CNS Disorders • Ischemic stroke • Pain • Vascular Neurology

Adenosine receptor agonist targets injury-specific astrocyte subtypes - therapeutic potential and pharmacodynamic biomarkers in a human trauma model. (Neuroscience 2024) - "In conclusion, AST-004 improves cell health, energy metabolism and astrocyte contact behavior with pharmacodymanic biomarkers indicating efficacy. This work offers early endpoint diagnostic tools and mechanistic insights to guide ongoing clinical trial design for improving TBI patient recovery."

Biomarker • PK/PD data • CNS Disorders • Vascular Neurology • GFAP

Lack of Interactions Between Alteplase/Tenecteplase and the Adenosine A1R/A3R Agonist AST-004. (PubMed, Stroke) - "In 2 different in vitro systems, AST-004 had no effect on the ability of alteplase or tenecteplase to generate plasmin, and AST-004 had no effect on the thrombolytic efficacy of alteplase to lyse blood clots in human blood. These studies indicate that there will be no interactions between AST-004 and tPAs such as alteplase or tenecteplase in patients with stroke undergoing thrombolytic therapy."

Journal • Cardiovascular • Thrombosis

Astrocyte Pharmaceuticals Announces FDA Clearance of its Investigational New Drug Application for AST-004 (GlobeNewswire) - "Astrocyte Pharmaceuticals...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 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 new study of AST-004 will first focus on treating those stroke patients with large vessel occlusions, offering hope to significantly diminish brain damage'."

IND • New P2 trial • CNS Disorders

Astrocyte Pharmaceuticals gets $6M to advance novel brain injury therapeutic (Healio) - '"Finding innovative ways to target inflammation in the brain will play an important role in the future of combination therapy and precision medicine for Alzheimer's disease,' Howard Fillit, MD...said in the release. 'Astrocyte's approach using AST-004 holds promise for reducing astrocyte-induced excess inflammation.'"

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Alzheimer's Drug Discovery Foundation Joins Astrocyte Pharmaceuticals’ $6M Pre-Series B Financing Round to Expand Development of Cerebroprotectant AST-004 (Businesswire) - "Astrocyte Pharmaceuticals Inc...nnounced an oversubscribed pre-Series B Bridge financing round of over $6M that was led by Dreavent Capital, and joined by the Alzheimer's Drug Discovery Foundation, and other investors. The funding will accelerate the clinical development of AST-004, a highly promising therapeutic candidate aimed at treating a broad array of acute brain injuries including stroke and traumatic brain injury (TBI), and further assess its potential in preclinical models of Alzheimer's disease....Astrocyte...preparing for Phase 2 efficacy studies in 2024." "

Financing • New P2 trial • Alzheimer's Disease • CNS Disorders

Alzheimer’s Drug Discovery Foundation Joins Astrocyte Pharmaceuticals’ $6M Pre-Series B Financing Round to Expand Development of Cerebroprotectant AST-004 (Businesswire) - '"Finding innovative ways to target inflammation in the brain will play an important role in the future of combination therapy and precision medicine for Alzheimer's disease,' said Howard Fillit, M.D...'Astrocyte's approach using AST-004 holds promise for reducing astrocyte-induced excess inflammation, which has the potential to provide a neuroprotective effect and may reduce the burden of beta-amyloid plaques in the brain, one of the traditional hallmarks of Alzheimer's.'"

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