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NEO212

NEO212 Provides a conjugation of POH with Temozolomide for treating GBM cancer tumors.

NEO212 is a conjugation of the DNA alkylating agent Temozolomide (TMZ) with a highly purified formulation of Perillyl Alcohol (POH).

TMZ remains the gold standard in treating anaplastic astrocytoma and glioblastoma multiforme cancers. It works by slowing or stopping the growth of cancer cells in your body. Recent studies have shown the 1-year and 2-year survival rates were 37.8% and 10.4% with radiation plus temozolomide versus 22.2% and 2.8% with radiation therapy alone. 

NEO212 was designed to potentially increase the efficacy of TMZ through intranasal delivery within the conjugated formulation.

INFORMATION
What is POH?

Perillyl Alcohol (POH) is a naturally occurring substance found in the essential oils of plants, such as citrus. It is already FDA-approved as a flavoring food agent.

POH has been shown to have antitumor activity against various cancer types including gliomas. POH actively appears to induce apoptosis in tumor cells without affecting normal cells and can revert tumor cells to a differentiated state. 

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How does NEO212 work?

NEO212 was created to potentially provide a better delivery mechanism for Temozolomide (TMZ), the gold standard for treating CNS-based cancers such as glioblastoma multiforme. It is estimated that close to 25 000 people in the United States will be diagnosed with primary cancerous brain and spinal cord tumors this year. Brain tumors account for 85% to 90% of all primary central nervous system (CNS) tumors. Since TMZ treatment is generally done through a series of oral dosages or intravenous infusion, its effectiveness is inhibited by the need for uptake to occur through the intestinal or circulatory system. Primary side effects include bone marrow suppression, nausea, vomiting, constipation, loss of appetite, and more.

NEO212 hopes to improve efficacy while minimizing the side effects currently associated with TMZ treatment alone.

How is NEO212 Administered?

Our research suggests that NEO212 can permeate across the Blood-Brain-Barrier (BBB). Three forms of delivery can be used to administer NEO212.

Internasal Delivery – NEO212 can be delivered intranasal through the trigeminal pathway to bypass the BBB. This ability allows NEO212 to be used for locally targeted delivery to the brain, eliminating the issues associated with oral and intravenous delivery methods.

Permeable BBB Delivery – Since NEO212 is a small, lipophilic (fat-soluble) molecule, it can permeate the BBB, primarily targeting the restriction of entry for large molecule substances (pathogens, viruses) and water-soluble compounds.

Intra-Arterial Delivery – NEO212 can be delivered intrathecally through a catheter positioned in the arterial pathway, which feeds the tumor and is injected into the tumor site, where it would be absorbed through the BBB into the cancerous tumor.

Mechanism of Action

NeOnc’s continued research has expanded the understanding of how POH works. In pharmacology, this is called the drug’s mechanism of action (MOA), which refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. An MOA generally describes the specific molecular targets to which the drug binds, such as enzymes or receptors, and how those receptor sites’ resultant actions have a specific effect that can impact the targeted disease.

The proposed MOA of NEO212 is shown below: