Clinical Study

Background

Pediatric High-Grade Gliomas (pHGGS) are a subset of High-Grade Gliomas (HGGS). A brain tumor is given the HGGSs designation if it is a glioma tumor formed in the brain or spinal cord through the abnormal growth of the glial cells, which surround, protect, and help with the functions of neurons, the cells that help send messages from your brain to the rest of your body. A high-grade rating indicates that the glioma is more advanced and rapidly growing.

When HGGSs are diagnosed in children aged one to fourteen, they are called Pediatric High-Grade Gliomas. The incidence of pHGGs is relatively low and occurs in 1.1–1.78 per 100,000 children. Despite the low incidence, pHGGs are responsible for over 40% of all childhood brain tumor deaths, and overall, they are the most common cause of tumor-related death in children. Although the structure of pHGGs is relatively the same as HGGs, the underlying genetic–molecular characteristics differ so much that many of the therapeutics used for adult gliomas have not yielded satisfactory results.

To address this problem, NeOnc is developing a path forward to advance research for its NEO100 formulation as a component for effective therapy for pHGGS. We have already begun the outlines for creating a study group for this application and are consolidating our strategy to gain the regulatory designations that will allow us to co-partner with two important strategic partners for the needed studies to follow.

Strategic Path

As pHGGS has such a low incidence rate and most current therapies are having limited effect on the disease, NeOnc has decided to apply to the FDA for an Investigational New Drug (IND) status for NEO100 to be used in this application. FDA grants IND Orphan drug status to a manufacturer to conduct human trials if the disease or condition affects fewer than 200,000 people in the United States and for which there is no effective therapy currently in the market to rest this disease.

To advance this, NeOnc is developing a study group of top research clinicians and experts in the pharma-therapy market development sector to gather the needed data and create the application for the FDA submission.

The group will use the analysis of variance (ANOVA) protocol to define the study targets for testing NEO100 in pHGGS. The ANOVA protocol is a five-category method for describing complex relations among variables. In particular, the group will be looking at those variables that pHGGS has in common with HGGS and those that are unique, as well as comparing these variables against the agency of the current therapeutics used to treat the disease.

As NeOnc already has an IND designation for its NEO100 formulation with GBM, there is high confidence that the approval for this variance on the IND will be granted. We hope to have the application submitted to the FDA by the first quarter of 2024.

Based on the approval of NEO100 for A pHGSS IND human study, NeOnc will begin a two-prong approach for the pathway to gaining a Rare Drug Approval from the FDA for the next phase of studies.

For this, NeOnce will be approaching both the California Institute for Regenerative Medicine (CIRM) and the Pediatric Neuro

Oncology Consortium (PNOC) for strategic alignment in the studies.

The CIRM is a California-based, taxpayer-funded entity whose function is to approve grants to groups that show novel research and solutions for accelerating the development of new stem cell-based therapies for chronic, debilitating diseases and disorders. The CIRM was created under the California Research and Cures Initiative, which was given $3 billion to fund its program.

PNOC is an international consortium with centers within the United States, Europe, Asia, and Australia. They are dedicated to bringing new therapies to children and young adults with brain tumors. The PNOC has an extensive background in developing clinical trials for the deadliest pediatric brain cancers and has created dedicated work groups for addressing many of the most malignant CNS-based cancers facing children. These include studies and trials for Diffuse Midline Glioma, High-grade Glioma, Low-grade Glioma, Medulloblastoma, Atypical Teratoid Rhabdoid Tumors (ATRT), Craniopharyngioma, Ependymoma, and Germ Cell Tumors.

NeOnc is looking to recruit clinical sites for a CIRM glioma stem cell study of pHGGS. Site in consideration include:

• USC
• UCSF
• Stanford
• UCLA
• UCSD

NeOnc is acquiring preclinical support from USC Glioma Group and hopes to submit its CIRM application by the first half of 2024 once the pHGSS IND has been approved. 

The total number of patients for the Rare Disease application study is anticipated to be ~40, with the exact number to be determined by the FDA in its IND approval. NeOnc is hoping to have its application for Rare Disease status submitted by August of 2024, with approval by October of the same year.