NEO100 is a highly purified form of the natural compound perillyl alcohol. NEO100 is currently undergoing clinical testing in the United States as Phase I/II trial. It is delivered intranasal and is the validation trial for the Fonseca Phase II performed in Brazil. It has IND in the US for the treatment of recurrent malignant gliomas. It currently has five active sites: University of Southern California (USC), Cleveland Clinic, University of Washington, University of Wisconsin, and Cleveland Clinic – Florida. NEO100 has Orphan drug and Fast Track status with the FDA.
Grade IV gliomas are among the most aggressive and deadly forms of brain cancers, and these patients face grim prognosis. The primary objectives of these clinical trials are: (i) to validate that daily sniffing of NEO100 (with a fitted face mask) is safe for the patients and does not cause severe side effects, and (ii) to evaluate the therapeutic impact of NEO100 on the patients brain cancer.
NEO102 is an isoform of the natural compound perillyl alcohol, called iso-perillyl alcohol. Our preliminary studies indicate promising anti-cancer activity of this compound, in particular against lung cancer cells. Patents granted in the US, Europe, and Japan.
NEO104 is a variant of the natural compound perillyl alcohol, where one hydrogen atom was replaced by its deuterium isotope. This deuterium-containing analog may have lower rates of metabolism, and hence longer-lasting therapeutic effects.
A provisional patent has been filed internationally.
TMZ-POH (NEO212) – NEO212 is the chemical conjugation of DNA alkylating agent temozolomide (TMZ) to POH. IP has been granted worldwide. TMZ continues to be the gold standard in the treatment of malignant gliomas. It has been published extensively in pre-clinical models for treatment of malignant gliomas, nasopharyngeal carcinomas, melanomas, and gliomas cancer stem cells (see articles included). NEO212 pre-clinically is 10x more potent than TMZ, 5x less toxic than TMZ, 5x more stable, and 3x better blood-brain barrier (BBB) penetrance compared to TMZ. Orphan drug status for malignant gliomas was granted. It has been tested in acute and chronic (small and large animal) testing at Charles Rivers (Montreal, Canada) in an oral formulation, with the dose-limiting toxicity of myelotoxicity. It has also been examined in non-GLP testing for intranasal delivery at Charles Rivers.
Rolipram-POH (NEO214) – NEO214 is the chemical conjugation of the phosphodiesterase type IV inhibitor (rolipram) with POH. Worldwide patent rights have been granted for this compound. Rolipram induces cytotoxicity in the mM range. NEO214 induces cytotoxicity in the uM range. Its main mechanism of action is as a cAMP modulator and ER stress. It is the next NTI compound, following NEO212, for trials. It is being tested (soon to be published) for gliomas, multiple myelomas.
In our earlier work, we had shown that rolipram exerted anticancer activity against brain cancer cells, although very high concentrations were required to achieve this effect. Our current work with NEO214 has revealed anticancer activity at much lower concentrations. A mere mix of the individual components, rolipram plus POH, is unable to achieve the striking anti-tumor outcomes of the conjugated molecule, demonstrating that therapeutic activity of NEO214 is greater than the sum of its parts. Intriguingly, we found that NEO214 stimulates the production of death receptor 5 (DR5), which makes cells highly sensitive to killing by TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). As a result, combining NEO214 with TRAIL may result in a highly effective cancer therapeutic regimen.
Valproic acid-POH (NEO216) – NEO216 is the chemical conjugation of valproic acid to POH. It works on the GABA pathway and is inhibitory to the invasion of Medulloblastoma cells. NEO216 has been awarded an American Brain Tumor Association grant and will have an NIH R01 grant application submitted this month. IP has been filed for a provisional patent.
3-bromopyruvate POH (NEO218) – NEO218 is a metabolic inhibitor and is less toxic than 3-bromopyruvate alone. A provisional IP has been filed. A research paper is pending publication.
Dopamine POH (NEO312) – NEO312 is the conjugation of Dopamine to POH. NEO312 demonstrated anti-Parkinsons activity in pre-clinical rodent models – when delivered intranasally. The patent application is pending.
NEO400 (TMZ POH Linoleic Acid) has demonstrated dramatic effects as an anti-wrinkle and anti-scarring compound in animal experiments. We are conducting additional experiments to determine efficacy in preventing melanoma formation via topical application.
If that data is successful, a determination will be made whether NEO400 could be added to consumer over the counter products that limit exposure to UV rays but provide no specific protection for cancer prevention.
NEO412 has been tested in a subcutaneous melanoma model on mice and demonstrated a successful decrease in tumor size using a cutaneous (topical) application. It also shows promise in actinic keratosis and skin melanomas in human volunteers.