NEW YORK (360Dx) – Diagnostics firm ImmunArray has spun off a new company, BrainBox Solutions, to commercialize tests for diagnosing and monitoring mild traumatic brain injury (mTBI).
ImmunArray announced last week that Donna Edmonds, the company's former chair and CEO, has taken over as chair and CEO of BrainBox, which launched in May of this year behind an $18 million Series A funding round led by BioVentures Investors.
Richmond, Virginia-based Brainbox aims to develop what Edmonds described as a "multi-modality product" combining point-of-care measurement of protein biomarkers linked to mTBI with additional tests like cognitive assessments to diagnose and monitor mTBI cases as well as determine a patient's risk of longer-term effects.
The MTBI biomarker space is a fairly crowded one, with companies including ABCDx, Abbott, Biodirection, Quanterix, and Banyan Biomarkers developing tests in this area. In February, the US Food and Drug Administration allowed Banyan Biomarkers to begin marketing its Brain Trauma Indicator, which measures the levels of the protein UCH-L1 and GFAP, to evaluate mild mTBI.
The Banyan, Biodirection, and ABCDx assays all aim to rule out patients as unlikely to have a concussion, allowing them to avoid a CT scan, which is commonly used to test patients suspected of mTBI. Brainbox, on the other hand, is positioning its tests for use after a CT scan to identify patients with mTBI missed by the head CT and to aid in monitoring those patients for adverse effects.
"We do not believe that an initial test to rule out a CT [like Banyan's] is going to be widely adopted and highly utilized," Edmonds said, noting that the company has determined through discussions with emergency department doctors that CT's wide accessibility, relatively low cost, and accuracy makes it unlikely to be replaced by a blood test.
"We believed that knowing whether you have mTBI or not, and what your expected outcome is at one month, ninety days, is where there is value," she said.
Edmonds noted that a percentage of patients who have negative CT findings nonetheless go on to develop mTBI symptoms.
"If you have a negative CT, you don't really know whether you're going to have concussion symptoms down the road or not," she said. "All you know is that you don't have a need for neurosurgical intervention."
A test like the one BrainBox is developing to identify patients with negative CT findings who are nonetheless at high risk of mTBI symptoms could allow these patients to access services and therapies that can improve their recoveries, Edmonds said.
"You can send folks for physical therapy, psychological intervention, occupational therapy. There are things you can provide people if you have a definitive diagnosis of mTBI, things you can do to make sure that he outcome at one or two months is maximized," she said.
BrainBox is not alone in focusing on the post-CT space in mTBI. It is also an area of emphasis for projects such as the TRACK-TBI initiative, an $18.8 million effort launched in 2014 by the National Institutes of Health and led by the University of California, San Francisco. Several members of BrainBox's scientific advisory board, including University of Pennsylvania Professor Ramon Diaz Arrastia and University of Pittsburgh Professor David Okonkwo, are also researchers on the TRACK-TBI project.
BrainBox's origins go back to 2012 when the company licensed a panel of brain injury markers developed by Johns Hopkins University researchers Jennifer Van Eyk (now at Cedars-Sinai Medical Center) and Allen Everett.
"We had the opportunity [in 2012] to license a unique biomarker portfolio in a market that we saw coming but that hadn't evolved at that point," Edmonds said.
She added that BrainBox has licensed a second set of brain injury biomarkers from the University of California, Los Angeles.
The company has also established an exclusive relationship with Boulder, Colorado-based point-of-care testing firm Mbio Diagnostics to develop and commercialize a POC mTBI test using their platform and BrainBox's markers, she said.
In 2014, ImmunArray received a $300,000 grant from the GE NFL Head Health Challenge to further develop the JHU panel. The same year it launched the HeadSMART study, a prospective clinical study that enrolled 500-plus patients with mTBI and followed them for up to six months, testing at multiple time points.
Last year, the company and its collaborators published a paper in Frontiers in Neurology detailing results of the study. The researchers looked at 334 mTBI patients with Glasgow Coma Scale scores of between 13 and 15 who were evaluated using CT at two emergency rooms in the JHU Hospital System along with 328 healthy controls. They collected blood samples from the mTBI patients within 24 hours of injury and used immunoassays to measure levels of three candidate protein markers, neurogranin (NRGN), neuron-specific enolase (NSE), and metallothionein 3 (MT3).
The researchers used a 179-patient subset for development of a mTBI test based on the three markers and a 153-patient subset for validation of the test. Diagnosis of mTBI was made based on criteria from the American Congress of Rehabilitation Medicine (ACRM).
A model consisting of the three markers distinguished between mTBI patients and healthy controls with an area under the curve of .88 (97 percent sensitivity and 53 percent specificity). Another model built using random forest classification combined the three markers with patient age and sex to deliver an AUC of .91 (sensitivity of 98 percent and specificity of 72 percent).
Applied to a separate validation set, this test performed with an AUC of .78. It correctly classified 91 percent of CT-positive patients and 75 percent of CT-negative patients. They also looked at its performance across patients with different levels of injury severity as defined by injury severity scores. In patients with more severe injury (ISS score of 16 or greater), the model was 88 percent accurate, while in patients with less severe injury (ISS score of 15 or lower), it had accuracy of 72 percent.
Brainbox plans to target the acute setting with its first test, which will be used to identify CT-negative mTBI patients who may benefit from additional outpatient intervention. Ultimately, the company plans to develop tests covering the post-acute periods, monitoring patient recovery over a period of months.
Edmonds said the company aims to submit its first test to the FDA in Q4 2019.