➤ Concussion and mild traumatic brain injury currently have no targeted therapy or treatment except rest.
➤ According to Oxeia Biopharmaceuticals Inc. CEO Michael Wyand, about 3 million people visit the emergency room for concussion injuries and symptoms, but are often sent home after diagnosis of concussion or mild traumatic brain injury due to lack of treatment options.
➤ Injured athletes such as football players rarely get sent to the emergency room for concussions.
➤ Repeated concussions have been linked to longer term consequences and conditions, such as Alzheimer’s, dementia and chronic traumatic encephalopathy.
CEO Michael Wyand
➤ Oxeia is pending initiation of a phase 2 trial of its treatment for concussions, OXE-103. OXE-103 was licensed from Daiichi Sankyo Co. Ltd., which had developed the molecule for a muscle-wasting condition.
Oxeia Biopharmaceuticals is a privately held biotechnology company founded in 2014 and based in San Diego. This interview has been condensed for clarity.
S&P Global Market Intelligence: What happens during a concussion?
Oxeia CEO Michael Wyand: Concussion is an injury where there's either a direct or indirect blow to the head. An indirect blow is something like a deceleration injury, where your body is moving forward at a high rate of speed and you suddenly stop, and your brain tends to bounce back and forth inside your skull.
The shockwaves cause all the cells in the brain to essentially depolarize and create a neurometabolic crisis. When that occurs, all parts of the brain start to fire, and because of that firing — the hyperexpectation phase — they burn through the available stores of energy in the brain. When the brain has been depleted of energy, you see the symptoms we associate with a concussion or mild traumatic brain injury: loss of consciousness, loss of understanding of where a person is, decreased cognitive abilities, nausea, sensitivity to light and sound, etc. That part of the injury occurs almost instantaneously and can take many days to recover.
Then, the shockwaves actually deform the brain, stretching and damaging some of the axons, which connect cells to the brain and carry information. That connectivity damage lasts the longest, and it results in what we call post-concussive syndrome. Those symptoms can go on for months, sometimes years after the injury.
Historically, we have overlooked and ignored this injury. I played contact sports when I was young and if I was hit and didn’t know where I was, if I could stand up and get back in the game, I was a hero. Yet, if I'd wrenched my knee, they'd probably carry me off and I'd get an MRI. And generally the first question professional athletes want to know is, when can I get back in the game? If they're playing contact sports, then they're clearly at risk of having another collision that would cause a similar injury.
How does OXE-103 work?
The molecule is a naturally occurring peptide hormone called ghrelin. Ghrelin crosses the blood-brain barrier, goes into the brain, and acts essentially to stimulate appetite. In situations where there is low energy, it has a neuroprotective effect. When there's low energy availability, your body starts to go into oxidative stress, especially your brain; ghrelin protects against the damage in cells from that oxidative stress, or low energy, and reestablish that normal energy balance in the brain.
Additionally, ghrelin has been shown to have some neurogenic properties. When you give ghrelin to normal animals, you see increases in the synaptic connections. So ghrelin would likely have a very positive benefit on that connectivity damage.
What will the OXE-103 clinical trials look like?
We chose to design the trial around the emergency room admitted population. That population tends to have more severe symptoms; usually they go there because someone has observed that they are showing significant symptoms with their injury.
The first part of our trial is an observational trial. Patients who come to the ER and then are discharged to home — we’re going to follow them and collect data on their symptoms and characterize the time course over which they start to show improvement.
The second part is an open-label trial in 30 to 40 patients. We're going to look at the tolerability, the treatment of patients at home, what kind of feedback we get during the enrollment period, and the number of patients who fit the inclusion criteria we've selected for the trial.
The third part will be a randomized controlled phase 2 trial. That trial will be placebo-controlled. So rather than launching into the large trial without the information up front, we're going to collect that information.
We have the drug manufactured, we have identified clinical sites and we've had the pre-investigational new drug application meeting with the U.S. Food and Drug Administration. Daiichi did 70-plus preclinical studies in their program, so all the animal safety was already completed; there is also a large safety database from their clinical trials.
Right now, everything is dependent on raising sufficient capital to be able to fund the study. As of today, we've raised $2 million privately.
What is the anticipated market for OXE-103?
We have the treatment in subcutaneous injection format, but we see this drug in an EpiPen format that would be available at the point of injury. Just the ER-admitted population is approximately a $2 billion market. If you start thinking about the sideline use, the ambulance use, the number of people getting concussions who don't seek medical care, we're talking about a market potential that reaches the multibillions, perhaps $6 billion.
What is Oxeia's exit plan, if any?
It's very likely that if we can establish clear activity of the drug, we'd be a very attractive target for a bigger company to acquire the asset, complete the development, and put it into their pipeline. Having said that, as the CEO, we need to have the plans to raise additional capital and take it forward ourselves into phase 3 trials and get approval. But I doubt very much we would get that far before a larger company shows interest in some type of a deal.