Technology
We have created a new category of drug delivery of therapeutics for CNS-based diseases that potentially have the ability to shift the outcomes for patients around the globe.

The Blood Brain Barrier
The Blood-Brain Barrier (BBB) is a semipermeable barrier of endothelial cells that prevents solubles in the circulating blood from crossing into the vertebral cavity and the central nervous system. The BBB is highly selective in that it allows oxygen and nutrient molecules to pass through but it prevents potentially harmful molecules such as pathogens, large molecules, and hydrophilic molecules (water-soluble) that could carry disease. The BBB is an incredibly intricate and essential part of the body’s defense mechanism for the protection of the CNS and the brain, but because of its nature, it is also a barrier to physicians in their ability to deliver lifesaving pharma-therapeutics to this area of the body. Since most pharma-therapeutics are large molecule formulations and/or water-soluble, they are unable to pass through the BBB effectively. This limits therapy to direct injectables such as intralesional and intratumoral chemotherapy or implanted Ommaya reservoir pumps. Unfortunately, many CNS and brain cancer tumors are too deep-rooted to be treated in this manner.
Understanding the Mechanics
The BBB is responsible for maintaining homeostasis, or equilibrium, in the brain. Anything that can interrupt this equilibrium via circulatory transport exchange is regulated by the BBB. The BBB accomplishes this through the configuration of endothelial cells which surround the network of arteries and capillaries in the brain. These cells create a fine mesh of tight junctions that prevent most large molecule structures from entering the brain.
In the case of therapeutics like Temozolomide (TMZ) which is the gold-standard drug for treating Glioblastoma Multiforme (GBM), its large molecular configuration and hypophilic (water-based) structure is prevented from directly entering into the brain tissue because of the BBB.

Additional Barriers
The traditional approach to delivering pharma-based therapeutics for CNS cancer has been either through IV infusion, oral ingestion, or intrathecal arterial delivery via an implanted drug pump such as an Ommaya reservoir.
In each of these methods, the main restriction to absorption of the drug into a tumor bed is the inability of the therapeutic to cross over the BBB, even when the drug is being delivered directly into the artery feeding the tumor as in the case of intrathecal delivery.
With IV infusion, there is the additional issue of the therapeutic being delivered systemically throughout the patient’s body which causes both unwanted side effects and dilution of the drug concentration once it does reach the brain.
Oral ingestion has all of the above problems but also adds the issue of requiring the drug to travel through the digestive system before being absorbed into the bloodstream. This process further delays and dilutes the efficacy of the drug to be effective.
The POH Solution
At the core of NeOnc’s novel technology is a proprietary synthesis of Perillyl Alcohol (POH), a naturally occurring compound that has shown efficacy in treating patients with recurrent gliomas. POH is a monocyclic terpene derived from the essential oils of a variety of plants including peppermint, sage, oranges, and lemongrass.
The molecular structure of POH consists of one hydroxide molecule (an oxygen and a hydrogen atom bonded together), combined with a hydrocarbon molecule ( a carbon atom bonded with three hydrogen atoms) and a methylene molecule (a carbon atom bonded with two hydrogen atoms).
Traditionally POH has been used as a common ingredient in many household products and is permitted by the U.S. Food and Drug Administration (FDA) as a food additive. Over the past decade, the medical community has focused on growing research on POH for its ability to act as a regulator for many of the neurologic pathways associated with cancer tumor cell growth. This includes the apoptosis pathway, Ras pathway, growth factors channels, AP-1 activity, cancer cell differentiation, cycle, and growth as well as other pathways where it acts as an antitumor inhibitor.
Because of its small molecular size and lipophilic (fat-soluble) structure, we believe POH is able to bypass the BBB effectively. This ability allows POH to be used for locally targeted delivery to the brain thereby eliminating the issues associated with oral and intravenous delivery methods. In addition, POH’s solvent properties allow it to encase other molecular structures to create hybrid combinatorial therapeutics that can then be delivered through the BBB thereby increasing their efficacy and ability to cure.
NeOnc has developed and researched its proprietary synthesis of POH for treating a variety of CNS-based diseases with a close focus on GBM. Through several research trials and published studies, its NEO100 and NEO212 formulations, we believe, have shown an ability to have a marked beneficial impact both as a therapeutic itself and as a transport mechanism for traditional chemotherapeutics such as TMZ when it is conjugated with that drug.
How It Works

The BBB restricts the passage of large or hydrophilic molecules into the brain. Generally, only lipophilic molecules with low molecular weight and positive charge can cross the BBB. Our research shows POH can permeate and pass through the BBB and, on its own, has been shown to induce apoptosis, or the restriction of cell growth, in established glioblastoma cell lines.
Our research in both animal and human trials, NEO100 has impacted tumor regression and progression for more than three years improving the survivability of both induced and recurrent GBM.
When conjugated with other therapeutics, we believe POH can provide an ability for the combined drug to effectively pass through the BBB without any loss of potency or dilution. In a study conducted by creating a combinatorial formulation of Herceptin with NEO100, it was found that the conjugated Herceptin/NEO100 formulation increased trastuzumab penetration across both in vitro BBB delivery and in vivo intravenous delivery resulting in brain tumor-selective accumulation of trastuzumab, without a detectable presence in normal brain tissue. In another study, intranasal delivery of Bortezomib (BZM), a proteasome inhibitor that is approved for the treatment of multiple myeloma, combined with NEO100 significantly prolonged the survival of tumor-bearing animals and concentrations in the brain of the combinatorial drug were higher than when BMZ was administered by itself.
