Title : Development of novel drug delivery pathways enabled by perillyl alcohol (NEO100), a monoterpene with multifaceted biomedical applications
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. (i) NEO100 can be delivered via intranasal applications, which exploits direct nose-to-brain transport, and an ongoing Phase 2a clinical trial with recurrent malignant glioma patients is generating intriguingly positive results. (ii) In preclinical brain cancer models, we have shown that intranasal NEO100 can act as a carrier to enable nose-to-brain delivery of other cancer drugs directly to the malignant lesions in the brain. (iii) When given via intra-arterial injection, NEO100 was shown to safely and reversibly open the blood-brain barrier (BBB) of mice, which enabled other cancer drugs circulating in the bloodstream to effectively enter the brain and kill brain cancer cells; in the absence of NEO100, these drugs were unable to cross the BBB and did not exert brain-targeted activity. (iv) In further applications, we covalently conjugated NEO100 to other, already established drugs. For example, conjugation of NEO100 to temozolomide, 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 I clinical trial has begun. — This talk will provide an overview of the multifaceted applications of NEO100 toward the development of more effective cancer treatments.
