Neonc Technologies (NASDAQ:NTHI) said its Phase II-A study of intranasal NEO100 met its primary endpoint in patients with recurrent IDH1-mutant Grade 3 and Grade 4 high-grade glioma, reporting a progression-free survival rate at six months of 48.9% versus a prespecified 20% historical benchmark.
The single-arm NEO100-01 trial enrolled 24 patients, including 21 with recurrent Grade 4 disease and three with Grade 3 disease, according to Chief Clinical Officer Dr. Josh Neman. The company reported that the progression-free survival result was statistically significant against the historical benchmark, with a p-value of 0.0047.
Study Results and Disease Control
Neman said 48.9% of patients remained progression-free at six months. The company also reported overall survival rates of 86.7% at six months, 60.9% at 12 months and more than half of patients alive at 24 months.
Five patients remained on the trial at the time of the presentation, including two patients who had remained on treatment for 24 months and 20 months, respectively. The company said its objective response rate, measured under RANO 2.0 criteria, was 8.3%, while 66.7% of patients achieved disease control, including partial responses and stable disease.
In combined Phase I and Phase II data, Neonc said 55% of 29 patients were long-term survivors, defined as surviving more than one year after recurrence. The company reported that median survival among those long-term survivors was 2.2 years, with a range from 1.2 years to more than eight years.
Chief Executive Officer and Executive Chairman Amir Heshmatpour said the Phase II study met its primary endpoint and characterized survival as the “standout result.” He said the treatment’s tolerability profile could support chronic dosing.
NEO100 Delivery Approach
NEO100 is an ultra-pure form of perillyl alcohol delivered through the nose using an inhalation mask and portable device. Founder, Chief Medical Officer and Chief Scientific Officer Dr. Thomas Chen said the approach is designed to use cranial nerve pathways to reach the brain while bypassing the blood-brain barrier.
Chen said NEO100 is being administered four times daily in the study. He described the treatment as non-invasive and said the company has identified multiple proposed mechanisms of action, including induction of endoplasmic reticulum stress, inhibition of sodium-potassium ATPase and effects on RAS signaling and cell-cycle proliferation.
The company’s Phase I dose-escalation study involved 12 patients with recurrent glioblastoma. Chen said the Phase I results prompted the company to examine biomarkers among longer-term survivors, leading to its focus on IDH1-mutant tumors for the Phase II-A study.
Scientific Advisory Board member Dr. Alexandra Miller said the early data represent a signal that should be evaluated in a substantially larger patient population. She noted that patients with recurrent, higher-risk IDH-mutant Grade 3 and Grade 4 gliomas have limited options, even as IDH inhibitors have expanded treatment choices earlier in the disease course.
“To have anything for these patients would be a huge accomplishment and really change the course of care for them,” Miller said.
FDA Meeting and Planned Phase III Study
Neonc said it plans to meet with the FDA to discuss a Phase III trial intended to support an accelerated-approval pathway. Neman said the company expects to propose a randomized design comparing NEO100 with lomustine, an approved chemotherapy used in recurrent glioma.
According to Neman, median overall survival would be the primary endpoint for a registrational study, while progression-free survival could potentially be considered in a prespecified interim analysis for accelerated approval. The company said it plans to seek FDA guidance on the trial design.
Scientific Advisory Board member Dr. Henry Friedman said the results were encouraging but said their importance would depend on whether they are confirmed in a subsequent study. He added that prolonged survival without a major radiographic response can occur with certain cancer treatments, potentially reflecting disease control rather than tumor shrinkage.
Neonc also said it has four clinical trials in progress across its NEO100 and NEO212 programs. NEO212 is an oral conjugate of NEO100 and temozolomide that the company said is in Phase II testing. Other NEO100 studies include programs in meningioma and pediatric brain cancer.
About Neonc Technologies (NASDAQ:NTHI)
Neonc Technologies Holdings, Inc develops novel molecular technology that provides enhanced targeted delivery of technologies for treating central nervous system diseases. Its lead products in development include NEO100, which is in Phase 2a clinical trials for treating glioblastoma; and NEO212, a covalently conjugated molecule combining the chemotherapeutic drug temozolomide with perillyl alcohol that is completed preclinical testing. The company was incorporated in 2023 and is based in Los Angeles, California.
