Pipeline

Drug Development for Neurological Disorders

ONP-002 for the Treatment of Traumatic Brain Injury

ONP-002 is a First-in-Class Enantiomeric-Neurosteroid being developed for the treatment of mild Traumatic Brain Injury (mTBI) aka concussion. A mTBI can occur following a direct hit to the head or a whiplash movement of the cervical spine. The injury is defined by stretching of the brain cells that leads to small tears in brain tissue including neurons and microvasculature. While many individuals recover within two-weeks of the injury there is a population of approximately 20% that can remain symptomatic for months or years, this is referred to as Post-Concussion Syndrome (PCS) and is linked to chronic neurological diseases including Alzheimer’s, Parkinson’s, and Chronic Traumatic Encephalopathy (CTE).

• Animal and cell culture models of neuronal injury show neuroprotective molecular and behavioral effects of ONP-002 within hours

• Animal studies have shown the drug to have an excellent safety profile when given intranasally and intravenously

• Intranasal administration in animals showed quick and significant distribution to all regions of the brain

• The intranasal formulation has been developed as a novel spray dried nanoparticle to enhance absorption and access to the brain parenchyma, bypassing the burdensome blood brain-barrier (BBB)

• The IP includes structure, synthetic preparation, and methods of use for ONP-002

ONP-002 - Mechanism of Action and Clinical Studies

ONP-002 diffuses intracellularly to induce steroid receptors found in neurons, glia, and the endothelium of the blood brain-barrier. The induction of the ONP-002 receptors activates multiple gene response elements leading to the production of mRNA transcripts and subsequently proteins that reduce inflammation, oxidative stress, and swelling. In addition, ONP-002 induces macro-autophagy to reduce the build-up of extra- and intra-cellular debris that can cause chronic neurological diseases associated with dementia. Since ONP-002 is not a GABAergic compound, it does not cause fatigue.

Oragenics has completed a SAD/MAD Phase I human safety study. ONP-002 was well-tolerated with no severe adverse events. PK studies showed a dosage increase in ONP-002 in blood plasma with overall low plasma levels due to intranasal delivery versus predicted higher levels with other forms of administration such as intravenous or oral.

Oragenics is currently preparing the launch of a Phase II clinical study evaluating the feasibility of using ONP-002 in the acute ER setting while analyzing blood biomarkers for prognosis and enrolment of more severe concussion along with cognitive, visual motor, patient reported outcomes, and disability scores to establish proof of concept for the use of ONP-002 - 2X a day for 5-days post brain injury.