Q&A: Developments in concussion therapies

DDW Editor Reece Armstrong speaks to Michael Wyand, Chief Executive Officer/Director, Oxeia Biopharmaceuticals about the development of the company’s treatment for concussion (OXE103) and the current lack of effective therapies for brain injuries.  

RA: Tell us how OXE103 works?  

MW: OXE103 (ghrelin) is a 28 amino acid neuro-peptide hormone that crosses the blood brain barrier and is responsible for maintaining brain energy homeostasis and neuroprotection related to neuronal cell preservation, axonal connectivity and decreased inflammation. OXE103 decreases reactive oxygen species (ROS) formation and the resultant oxidative damage which can lead to persistent inflammation in the brain post concussive injury. OXE103 also has neurogenic effects on brain circuitry to improve connectivity. Similar to other hormones with pleotropic activity, OXE103 effects are multimodal making it uniquely positioned to treat the constellation of damage resulting from concussion/mTBI. 

RA: Why are there currently no effective pharmacological FDA-approved treatments for concussion?

MW: Historically, efforts to develop therapeutics for brain injury have focused on moderate and severe TBI (traumatic brain injury). Rest in a darkened room was thought to be sufficient to treat the mild form of TBI known as concussion. We now know that concussions can have very severe consequences and, in some cases, can result in severe post-concussion symptoms which might last for weeks to months or even years. Concussions are not associated with significant structural damage that can be observed on CT scans or routine clinical MRI examination. There are now a number of companies at various stages of developing a concussion drug. Oxeia’s is the first to be in Phase II trials. 

RA: How encouraged are you by the results of the Phase IIa pilot study?

MW: We are very encouraged about the responses to OXE103 that were observed in our Phase IIa study. The data support moving forward with a larger Phase 2b study in the post-concussion population. The Phase IIa study not only provided a robust signal of efficacy but also provided experience with running trials in this patient population with the endpoints that assess the way patients feel and function after treatment. 

RA: How important would a drug like OXE103 be to industries such as sports where head-injuries can be common?

MW: Currently there are no available therapies to treat the underlying damage from concussive injury. We know that even a single concussion can lead to prolonged neurometabolic/connectivity changes and that multiple concussions are related to more severe outcomes including CTE and dementia. Athletes, especially those playing contact sports, are constantly at risk for repetitive concussive injury. They are highly conditioned and motivated to return to play as soon as possible. The typical “civilian” who falls down the stairs at home is unlikely to ask their physician “when am I cleared to fall down the stairs again.” Both groups need an effective therapy, but athletes experience a unique increased risk due to a lack of an effective therapy.  

RA: What are some of the challenges of developing a drug to treat the neurometabolic cascade and axonal injury seen with concussion?

MW: The team at Oxeia is very excited to be working in an indication with a huge unmet medical need – the significance of which has been historically underestimated. The challenge is to work with regulators, clinicians and patients to define the appropriate pathway to a safe and effective drug approval. Currently concussions, similar to many neurologic indications such as migraines, Parkinson’s disease, ALS, and Alzheimer’s disease, among others, rely on subjective endpoints to assess a treatment response. The brain controls functions across cognition, emotions and physical functions, meaning the endpoints must be selected to encompass various symptoms that manifest themselves in a particular patient. Luckily the pathways for using subjective assessments for drug approval are well trodden and available for application to our program. 

RA: Is OXE103 more beneficial to post-concussion sufferers or can it be effective in all concussion patients?

MW: The hallmarks of concussion injury – oxidative damage to neurons, inflammation and decreased/damaged connectivity define both the acute injury and the chronic persistent post-concussive condition. Our current target is patients who are within 28 days of their injury and remain highly symptomatic without significant evidence of resolution. As part of our expanded approval strategy, we will proceed with trials in acutely injured patients within 24 hours of injury in addition to the post-concussion population. 

RA: For post-concussion sufferers, is OXE103 effective even when a patient has gone a long time living with symptoms?

MW: As with any injury, therapeutic intervention close to the time of injury is likely to be more effective than allowing an injury to become chronic. Our vision is that the availability of an effective concussion therapy will make patients suffering long term debilitating symptoms a thing of the past. 

RA: How important is it that concussion sufferers have a drug available on the market compared to the current standard of care?

MW: The current standard of care includes various forms of physical, cognitive and vestibular therapy with appropriate use of approved therapeutics to treat headache, nausea or other symptoms. No current therapy is available to reduce the acute and ongoing oxidative damage and effects on connectivity. Optimally an effective drug would reduce the long-term risks of CTE and dementia which result from cumulative damage.  

RA: What are the next steps for Oxeia Biopharmaceuticals?

MW: Oxeia is currently raising funds to conduct a larger Phase IIb that will significantly advance us on the path to an approved drug. The current funding environment for early-stage biotech companies is extremely challenging and is focused on later stage de-risked programs. Indications in oncology, gene therapy, AI platforms and rare diseases are an exception and are still garnering investors.  

Oxeia’s next steps are to recruit investors who recognise the huge unmet medical need for this historically underestimated injury, are excited to innovate in a new target indication and are passionate about making a difference. Concussion is a condition that touches everyone, young and old, athlete and non-athlete. Rest Is not Enough! 

Biography  

Dr Wyand’s decades of experience managing and building life science companies includes roles as CTO and President/COO, Epirus Biopharmaceuticals; R&D head at Percivia, BioAssets Development and Therion Biologics; and President/CSO, Mason Laboratory. Wyand trained in comparative pathology at Harvard Medical School and holds DVM, PhD in Pathology and BS. 

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