BRAINBox Solutions Announces Publication in JAMA Network OPEN of Major Analysis of Initial HeadSmart II Trial Concussion Patients

Study identified baseline clinical characteristics and those subjects with subsequent persistent post-concussive symptoms

Company also announces four new U.S. patents covering its concussion diagnostic/prognostic technology

RICHMOND, Va., Oct. 17, 2025 /PRNewswire/ -- BRAINBox Solutions today announced the publication in JAMA Network OPEN of a major analysis of the first 1,000 patients with suspected concussion (mild traumatic brain injury or mTBI) in its pivotal, HeadSMART II study of its initial test, BRAINBox TBI, for concussion diagnosis and prognosis. The analysis, the largest of its kind, identified patient characteristics at the first medical encounter shortly after injury that are associated with consequential, persistent (30-days) symptoms, setting the stage for its test for diagnosis and prognosis.

"mTBI is a potentially serious condition and distinguishing which patients with acute mTBI are likely to recover and be symptom free in 30 days and which patients will suffer persistent symptoms for 30 days or more is extremely difficult," said W. Franklin Peacock MD FACEP, Principal Investigator, and Professor of Emergency Medicine in the Department of Emergency Medicine at Baylor College of Medicine. "There are currently no objective and accurate standard of care tests to identify ER patients at risk of persistent symptoms and who may benefit from therapeutic interventions. The HeadSmart II clinical trial was designed specifically to evaluate the potential of such an objective and quantitative test."

The HeadSmart II study supports BRAINBox TBI, which has received Breakthrough Device Designation from the FDA; the trial was designed in collaboration with the U.S. Food and Drug Administration and leaders in emergency medicine, and neurotrauma. The HeadSMART II trial is evaluating the diagnostic and prognostic potential of BrainBox TBI, a multimodal test that combines clinical data, neurocognitive testing, symptom reporting, and blood-based biomarkers, with proprietary AI algorithms to generate an objective score for diagnosis up to 96 hours from the time of injury. The trial has included more than 1,650 subjects, with follow-up on symptoms occurring up to 90 days post-event.

The just published analysis focused on early clinical characteristics associated with persistent symptoms at 30 days in 803 of the first 1,000 patients in the HeadSmart II trial who had completed the first 30-day follow-up period. The study population was divided roughly equally between males (50.3%) and females (49.7%). The study found that selected mTBI patients had persistent symptoms at 30 days, which remained constant over time: from 32.1% at presentation to 35.5% at 14 days, and 29.3% out to 30-days. The headache rate decreased from 73.5% at presentation, to 62.5%. Additional analysis of the 30-day follow-up data found a group of consistent symptoms or factors at initial presentation that were significantly associated with an increased probability of symptoms at 30 days. The company will report findings from the 90-day follow-up in the future.

The patients included in the analysis were seen in an Emergency Department (ED) within a median of 90 minutes after injury and completed a 30-day follow-up. "The study is unique and critical in the short time between injury and presentation, because symptoms change over time and intervention following early identification of patients at risk of 30-day symptoms is likely to have the greatest impact on function," noted Dr. Peacock.

"In elderly patients, primarily over 65 years of age, there is a similar diagnostic/prognostic gap in distinguishing mTBI symptoms from neurogenerative conditions such as dementias, including Alzheimer's disease," said co-author Damon Kuehl, MD, Vice Chair for Research in the Department of Emergency Medicine for Carilion Clinic and Vice Chair of the Virginia Tech Carilion School of Medicine's Department of Emergency Medicine. "The elderly cohort in the overall HeadSMART II study suggests these factors may also aid in distinguishing these conditions."

"Suspicion of a traumatic brain injury is among the most common reasons for Emergency Department visits with more than 5.2 million such instances annually in the U.S. alone," said Marc E. Goldberg, a member of BrainBox's Board of Directors and founder/Managing Partner of BioVentures MedTech Funds. "The company has an enormous opportunity to create a new standard of care for mTBI, and its underlying approach – combining blood biomarkers, functional testing and AI -- has shown considerable promise in the diagnosis and prognosis of other challenging neurological conditions as well."

"BrainBoxTBI has great potential to fill a key gap in identifying patients who actually have an injury, and especially in mTBI management," said Donna Edmonds, BRAINBox Solutions' CEO. "With the emergence of multiple mTBI therapeutics in development, the test has promise in patient selection for clinical trials by identifying those at high risk for consequential, persistent symptoms and for monitoring treatment response." She noted that earlier this year BrainBox entered into a collaboration with Oragenics to build a comprehensive test-to-treat platform by combining BRAINBox's multi-marker/multimodality diagnostic capabilities with Oragenics' novel mTBI therapeutics in development.

The JAMA Network OPEN study is entitled, "Factors Associated with Persistent Symptoms Following Mild Traumatic Brain Injury." The design and oversight of the study is being conducted by leading experts in emergency medicine and neurotrauma. The authors, in addition to Drs. Peacock and Kuehl include Ramon Diaz-Arrastia, MD, PhD, Professor of Neurology, Director, Clinical TBI Research Center, University of Pennsylvania, Perelman School of Medicine; Martin Than, MD, Director of Emergency Medicine Research, Christchurch, New Zealand; Chad Canon, MD, Professor of Emergency Medicine, University of Kansas Medical Center; Adam J. Singer, MD, Distinguished Professor of Emergency Medicine, Renaissance School of Medicine at Stony Brook University of New York; Nizanin Mirashahi PhD, Director of Data Analytics, BrainBox Solutions; Justin Weppner, D.O., M.Ed, CBST-AP, Section Chief Physical Medicine and Rehabilitation; and Robert Gerwein PhD, Biostatistician. Drs. Peacock, Kuehl and Diaz-Arrastia, also serve on the BRAINBox Solutions Scientific Advisory Board (SAB). BrainBox assembled the HeadSMART II database and allowed access to the dataset. There was no funding support for the analysis or manuscript creation.

Four New Patents Issued
The Company also announced that the U.S. Patent and Trademark Office has awarded four new patents covering technologies for diagnosis, monitoring, and prediction of acute disorders, such as mTBI and intracerebral hemorrhage, and Alzheimer's Disease. The patents cover both biomarkers as well as use in combination with advanced imaging technologies. The patents further strengthen the company's intellectual property position, which now includes 24 issued patents.

About the HeadSMART II Trial and BrainBox TBI
The overall HeadSMART II trial is evaluating the potential of the BRAINBox TBI test as the first objective quantitative test to aid in the diagnosis of concussion and to provide an assessment of the risk of post-concussive symptoms. BRAINBox TBI is multi-modal test that combines clinical data, neurocognitive testing, symptom reporting and blood-based biomarkers, with proprietary AI algorithms to generate an objective score for diagnosis up to 96 hours from the time of injury. In addition, a prognosis report is generated, providing the likelihood of injury-related symptoms occurring 30 days and up to three months after the event.

The trial has included over 1650 subjects with suspected mTBI, meeting the statistical requirements of the study protocol. The study's primary endpoints include mTBI (also called acute traumatic encephalopathy or ATE) diagnosis, as determined by the BRAINBox TBI test, compared with the Gold Standard diagnosis and the test's ability to predict persistent symptoms up to 30 and in the future, 90 days after an ATE diagnosis.

About BRAINBox Solutions
BRAINBox Solutions, Inc is developing the first AI‐enabled, multi‐modality approach for the diagnosis and prognosis of Mild Traumatic Brain Injury, commonly referred to as a concussion. The company seeks to establish a clinical bests‐practice standard for the diagnosis and prognosis of concussion. The product incorporates a panel of proprietary, patented blood biomarkers that can be read in a few moments on a point‐of‐care instrument or using standard laboratory systems, as well as neurocognitive testing, to provide a single‐system score that measures the severity of the injury and post-concussive symptoms. The company is led by key physicians and scientific thought leaders in the field and an experienced, clinically focused management team. Learn more at: www.brainboxinc.com

For more information, contact:
Donna Edmonds
CEO
1‐804‐724‐0009

SOURCE BRAINBox Solutions, Inc.