perillyl alcohol (NEO100) / NeOnc Technologies - LARVOL DELTA

Potent Therapeutic Activity of NEO212 in Preclinical Models of Human and Canine Leukaemia and Lymphoma. (PubMed, Vet Comp Oncol) - "We are developing a novel anticancer agent, NEO212, a conjugate of two cancer drugs, the alkylating agent temozolomide (TMZ) and the monoterpene perillyl alcohol (POH). At the same time, NEO212 is well tolerated in dogs at dosages higher than those that achieved therapeutic activity in mouse models. Our study introduces NEO212 as a novel oral cancer drug candidate for both human and veterinary oncology applications."

Journal • Preclinical • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Oral Cancer • Solid Tumor

Optimization of Eudragit RS100 Nanocapsule Formulation for Encapsulating Perillyl Alcohol and Temozolomide Using Design of Experiments. (PubMed, ACS Nanosci Au) - "Encapsulation efficiencies were 3.7% for POH and 28.5% for TMZ. This nanoencapsulated delivery system offers a promising approach for glioblastoma treatment, potentially enhancing clinical outcomes and reducing treatment-associated toxicity."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

NeOnc Technologies Holdings, Inc. Expects Full Enrollment in Promising Phase 2a Trial of NEO100-01 for Malignant Gliomas in September (GlobeNewswire) - "NeOnc Technologies Holdings...announced that it expects full enrollment in its Phase 2a clinical trial for its lead therapeutic candidate, NEO100-01 in September. Only six patients remain to complete the trial’s 25-patient enrollment target. This landmark trial, for which read-out data is expected in early 2026, investigates NEO100, a proprietary, highly purified version of perillyl alcohol, delivered intranasally, a non-invasive method designed to bypass the blood-brain barrier through the olfactory and trigeminal nerves."

P1/2 data • Trial status • Glioma

FDA Gives RPDD to NEO100 for Pediatric-Type Diffuse High-Grade Glioma (OncLive) - "The FDA has granted rare pediatric disease designation (RPDD) to perillyl alcohol (NEO100) for the treatment of patients with pediatric-type diffuse high-grade gliomas (HGG)....A phase 1b dose-finding trial...which has yet to begin recruiting patients, will assess NEO100’s safety, brain tumor delivery, and pharmacokinetics in patients with pediatric-type diffuse HGG."

FDA event • Trial status • Glioma

NeOnc Technologies Expands Global Clinical Trial Network with CBCC Global Research to Accelerate Study of Brain Cancer Treatments (GlobeNewswire) - "NeOnc Technologies Holdings, Inc...announced a strategic partnership with CBCC Global Research (CBCC), a premier full-service clinical research organization (CRO). This collaboration will expand NeOnc’s clinical trial capabilities in India, facilitating the advancement of its development-stage neuro-oncology treatment....CBCC will initially recruit for the NEO100-01 Glioblastoma (GBM) clinical trial, which is a Phase 2a study evaluating the survival impact and tolerance of intranasal NEO100, an ultra-purified perillyl alcohol with a focus on the IDH1 mutation component in Grade 3 and 4 GBM tumors....'We are focused on completing our Phase 2 NEO100-01 enrollment this year, with a readout expected 6 to 8 months after that'."

Commercial • P2a data • Glioblastoma

Therapeutic Delivery of circDYM by Perillyl Alcohol Nanoemulsion Alleviates LPS-Induced Depressive-Like Behaviors. (PubMed, Adv Sci (Weinh)) - "This effect is achieved by reducing the CD11b+CD45dim microglia population and iNOS expression, restoring the expression of protein-95 (PSD-95) and synaptophysin. These findings indicated that PANE represents an efficient platform for delivering circRNAs to the brain, and intranasal administration of PANE2-4-circDYM is a promising strategy for ameliorating LPS-induced depressive-like behaviors."

Journal • CNS Disorders • Depression • Genetic Disorders • Infectious Disease • Mental Retardation • Oncology • Psychiatry • ITGAM • SYP

Optimized mucus adhesion and penetration of lipid-polymer nanoparticles enables effective nose-to-brain delivery of perillyl alcohol for glioblastoma therapy. (PubMed, Drug Deliv Transl Res) - "In vitro assays demonstrated that LPNP-POH increased the cytotoxicity and reduced the tumor growth of U87MG glioma cells. These results highlighted that the engineered formulation, with optimized mucoadhesiveness and mucus penetration properties, improved nose-to-brain delivery of POH, offering a promising potential for glioblastoma therapy."

Journal • Brain Cancer • CNS Disorders • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Patient with recurrent grade 4 astrocytoma responding favorably to intranasal delivery of NEO100, highly pure perillyl alcohol: illustrative case. (PubMed, J Neurosurg Case Lessons) - "The authors present a case in which IN cancer therapy with NEO100 was well tolerated and was associated with striking tumor regression, providing further evidence that this novel conceptual approach to cancer therapy might become useful for the improved treatment of recurrent glioma. https://thejns.org/doi/10.3171/CASE24683."

Journal • Anaplastic Astrocytoma • Astrocytoma • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • IDH1

Bringing intranasal drug delivery for malignancies in the brain to market. (PubMed, Expert Opin Drug Deliv) - No abstract available

Journal • Brain Cancer • CNS Tumor • Glioma • Meningioma • Oncology • Solid Tumor

Safety and Efficacy Study in Recurrent or Progressive Grade III or IV IDH1 Mutated Glioma (clinicaltrials.gov) - P1/2 | N=49 | Recruiting | Sponsor: Neonc Technologies, Inc. | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • IDH1

A Study of the Safety, Dosing, and Delivery of NEO100 in Patients with Pediatric Brain Tumors (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Neonc Technologies, Inc. | Trial completion date: Oct 2024 ➔ Oct 2025 | Initiation date: May 2024 ➔ Dec 2024 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Trial completion date • Trial initiation date • Trial primary completion date • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

NeOnc Technologies Begins Enrollment for Phase 2 Clinical Trial of NEO100-02 for Patients Afflicted with Meningioma, Marking Second Concurrent Phase 2 Study of Leading CNS Cancer Drug Candidate (GlobeNewswire) - "NeOnc Technologies Holdings, Inc...has begun patient enrollment for the Phase 2 clinical trial of NEO100-02, the company’s first of two drug candidates proceeding through four concurrent clinical trials for various indications and patient populations. The Phase 2 study of NEO100-02 seeks further safety and preliminary evidence of the biological effects of the novel drug on patients afflicted with residual, progressive or recurrent high-grade meningioma."

Enrollment open • Meningioma

NEO212, temozolomide conjugated to NEO100, exerts superior therapeutic activity over temozolomide in preclinical chemoradiation models of glioblastoma. (PubMed, Neurooncol Adv) - "NEO212 is a candidate drug to potentially replace TMZ within the standard Stupp protocol. It has the potential to become the first chemotherapeutic agent to significantly extend overall survival in TMZ-resistant patients when combined with radiation."

Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Hematological Malignancies • Oncology • Solid Tumor

Therapeutic effect of NEO400, perillyl alcohol conjugated to linoleic acid, in a mouse model of UV-induced skin damage. (PubMed, Photochem Photobiol) - "None of these skin-protective effects could be achieved with Aloe vera gel, a popular and widely used post-exposure remedy. Our study suggests that NEO400 holds potential as a regenerative treatment for excessively UVR-exposed skin."

Journal • Preclinical

Molecular pharmacology and therapeutic advances of monoterpene perillyl alcohol. (PubMed, Phytomedicine) - "This review systematically summarizes the recent advances in POH and highlights its therapeutic effects and potential mechanisms as well as the clinical settings, which is helpful to develop POH into functional food and new candidate drug for prevention and management of diseases. Future studies are needed to conduct more biological activity studies of POH and its derivatives, and check their clinical efficacy and potential side effects."

Journal • Review • Asthma • Immunology • Metabolic Disorders • Oncology • BAX • BCL2 • CASP3 • CCND1 • CDKN1A • HIF1A • NLRP3 • NOS3 • PARP1 • STAT3

Pharmacokinetics assessment of intranasal NEO100 treatment on blood-brain barrier disruption and brain penetration of drugs in rodent brain (AACR 2024) - "Co-administration of IN NEO100 with ZN-c3, everolimus, and infigratinib increases their brain and plasma exposure. As a result, no significant increase in brain-to-plasma partition was registered for any of the three drugs tested in this study. IN NEO100-mediated increase in brain drug concentration was independent of BBB disruption"

PK/PD data • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

A Study of the Safety, Dosing, and Delivery of NEO100 in Patients With Pediatric Brain Tumors (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Neonc Technologies, Inc.

New P1 trial • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor

Enhancing the Antiproliferative Activity of Perillyl Alcohol against Glioblastoma Cell Lines through Synergistic Formulation with Natural Oils. (PubMed, Curr Pharm Des) - "The findings indicated that the antiproliferative effect of POH-loaded Nanoemulsion (NE) could be used as a possible anticancer therapy for glioblastoma in vitro, particularly when paired with the tested natural oils. Before asserting that this delivery technique is appropriate for glioblastoma therapy, additional in vitro and in vivo investigations are required."

Journal • Preclinical • Brain Cancer • CNS Tumor • Gastrointestinal Disorder • Glioblastoma • Glioma • Oncology • Solid Tumor

Activation of Epstein-Barr Virus' Lytic Cycle in Nasopharyngeal Carcinoma Cells by NEO212, a Conjugate of Perillyl Alcohol and Temozolomide. (PubMed, Cancers (Basel)) - "The Epstein-Barr virus (EBV) is accepted as a primary risk factor for certain nasopharyngeal carcinoma (NPC) subtypes, where the virus persists in a latent stage which is thought to contribute to tumorigenesis. Inclusion of the antiviral agent ganciclovir synergistically enhanced the cytotoxic impact of NEO212, pointing to a potential combination treatment for EBV-positive cancers which should be explored further. Overall, our study establishes NEO212 as a novel agent able to stimulate EBV's lytic cycle in NPC tumors, with implications for other virus-associated cancers."

Journal • Epstein-Barr Virus Infections • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate. (PubMed, Autophagy) - "When combined with chloroquine and TMZ, the anticancer impact of NEO214 is further potentiated and unfolds against TMZ-resistant cells as well. Taken together, our findings characterize NEO214 as a novel autophagy inhibitor that could become useful for overcoming chemoresistance in glioblastoma.Abbreviations: ATG: autophagy related; BAFA1: bafilomycin A; BBB: blood brain barrier; CQ: chloroquine; GBM: glioblastoma; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MGMT: O-6-methylguanine-DNA methyltransferase; MTOR: mechanistic target of rapamycin kinase; MTORC: MTOR complex; POH: perillyl alcohol; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TMZ: temozolomide."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor • LAMP1 • SQSTM1 • TFEB

Incorporation of Perillyl Alcohol into Lipid-Based Nanocarriers Enhances the Antiproliferative Activity in Malignant Glioma Cells. (PubMed, Biomedicines) - "The size, surface charge, and lipid composition of the LNCs make them promising for drug delivery across the BBB. Detailed pharmacokinetic and pharmacodynamic assessments, including the evaluation of BBB penetration, are necessary to better understand the compound's distribution and effects within the brain."

Journal • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

NeOnc Technologies Formalizes Exclusive Global IP Licensing Agreement with USC for Enhanced Method of Delivering Novel Pharma Therapeutics to the Brain (GlobeNewswire) - "NeOnc Technologies Holdings, Inc...has formally secured exclusive worldwide rights from the University of Southern California (USC) to an extensive intellectual property portfolio of proprietary and patented chemotherapy agents and methodologies that have demonstrated positive effects in laboratory tests on various types of cancers and in clinical trials treating malignant gliomas....Covering 135 U.S. and international patents issued and applications pending, the licensing agreement is considered the largest IP transfer of its kind for the development and commercialization of chemotherapies related to brain and CNS diseases. The license covers agent composition and methods of use technology, including an enhanced method of delivering pharma-based therapeutics to the brain."

Licensing / partnership • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Oncology • Solid Tumor

Intranasal Delivery of miR133b in a NEO100-Based Formulation Induces a Healing Response in Spinal Cord-Injured Mice. (PubMed, Cells) - "We found that IN delivery of miR133b/Ago2 (1) reaches the lesion scar and co-administration of miR133b with NEO100 facilitated the cellular uptake; (2) enhanced the motor function and addition of NEO100 potentiated this effect and (3) targeted FN1 expression at the lesion scar. Our results suggest a high efficacy of IN delivery of miR133b/Ago2 to the injured spinal cord that translates to improved healing with NEO100 further potentiating this effect."

Journal • Preclinical • CNS Disorders • Fibrosis • Orthopedics • FN1 • MIR133B • NECTIN1

NeOnc Technologies Engages Anova Enterprises to Pursue Pediatric Brain Tumor Indication and FDA Fast-Track Status for NEO100 (GlobeNewswire) - "NeOnc Technologies Holdings, Inc...has expanded its engagement of Anova Enterprises to pursue a pediatric indication for NEO100, an enhanced method of delivering pharma-based therapeutics to the brain designed for the treatment of brain and central nervous system (CNS) diseases....As part of the new pediatric program for NEO100, Anova will prepare the application to obtain FDA Fast-Track and Rare Pediatric designations, and develop a clinical pediatric study plan. The program is expected to build upon the early success researchers have seen in NEO100 studies of adult patients with IDH1 mutated brain tumors (another type of high-grade glioma) and with compassionate use."

Licensing / partnership • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Enhanced brain entry of checkpoint-inhibitory therapeutic antibodies facilitated by intraarterial NEO100 in mouse models of brain-localized malignancies. (PubMed, J Neurosurg) - "BBB opening by IA NEO100 facilitates brain tumor access by checkpoint-inhibitory antibodies and enables their therapeutic activity, along with increased levels of T-cell recruitment."

Checkpoint inhibition • Journal • Preclinical • Brain Cancer • CNS Tumor • Glioblastoma • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CD8