Perillyl alcohol (NEO100), a monoterpene with versatile applications for cancer therapy

Title : Perillyl alcohol (NEO100), a monoterpene with versatile applications for cancer therapy

Abstract:

Perillyl alcohol is a naturally occurring monoterpene related to limonene. We have synthesized a clinical-grade version, called NEO100 (NeOnc Technologies, Inc., Los Angeles, California), which has revealed a variety of highly promising characteristics that we are exploring toward the development of improved cancer-therapeutic regimens. NEO100 can be delivered via intranasal applications, which exploits direct nose-to-brain transport, and an ongoing clinical Phase 2 trial with recurrent glioblastoma patients is generating promising results. In preclinical brain cancer models, we have further shown that intranasal NEO100 can act as a carrier to bring along other cancer drugs, such as bortezomib, for improved delivery to the malignant lesions in the brain. When given via intra-arterial injection, NEO100 was shown to safely and reversibly open the blood-brain barrier (BBB) of mice, which enables other cancer drugs circulating in the bloodstream to effectively enter the brain and kill brain cancer cells; in the absence of NEO100, these drugs are unable to cross the BBB and do not exert brain-targeted activity. In further applications, we covalently conjugated NEO100 to several other, already established drugs. For example, conjugation of NEO100 to temozolomide (TMZ), an alkylating agent, resulted in a novel fusion compound called NEO212 (NeOnc Technologies). Our studies in diverse preclinical tumor models established that NEO212 is well-tolerated and highly effective against different cancer types, and a Phase 1 clinical trial has begun. — This talk will provide an overview of our research into the versatile applications of perillyl alcohol/NEO100 toward more effective cancer treatments. 

Audience Take Away Notes:

• Perillyl alcohol (POH) enables direct nose to brain transport of drugs
• POH is able to open the blood-brain barrier (BBB)
• Conjugation of POH to established drugs enables BBB penetration
• POH has entered clinical trials as NEO100

Biography:

Axel H. Schonthal, PhD, is Associate Professor in the Department of Molecular Microbiology and Immunology at the Keck School of Medicine of the University of Southern California (USC) in Los Angeles. He is also Associate Dean for Biomedical Masters Programs, and Faculty Fellow of the USC Center of Excellence in Teaching. He obtained his PhD from the University of Karlsruhe, Germany, and did his postdoc at the Cancer Center of the University of California in San Diego (UCSD). At USC, he pursues the development of novel anticancer agents and novel delivery methods to improve cancer therapeutic efficacy. As of 2024, he has authored over 200 scholarly articles and chapters with an H-Index of 53.