▶U.S. UCSF researchers identified strong anti-tumor synergy effect between pegsebrenatide and targeted anticancer drug 'borasidenib' in IDH mutant brain tumors ▶Induced direct death of cancer cells beyond the 'tumor growth inhibition' limit of existing targeted treatments, confirmed tumor shrinkage and extended survival period in preclinical studies ▶Expected to expand the treatment area and value of new drugs to intractable rare brain cancer following neurological diseases such as Parkinson's disease and multiple sclerosis
D&D Pharmatech's (347850) new drug candidate 'Pegsebrenatide (NLY01)' was shown to induce cancer cell death in IDH mutant glioma and increase survival time in preclinical studies in combination with targeted anticancer drugs. As a result of suggesting the possibility of treating brain tumors with a drug that has been developed as a treatment for neurological diseases, the company is considering pursuing follow-up clinical trials.
D&D Pharmatech announced on the 23rd that the results of a study on the combination of pegsebrenatide, a long-acting GLP-1 receptor agonist, and the targeted anti-cancer drug 'vorasidenib' were published on 'bioRxiv', a life science paper pre-release platform.
This study was led by a research team led by Professor John de Groot of the Department of Neurosurgery and Professor Pavitra Viswanath of the Department of Radiology and Biomedical Imaging at the University of California, San Francisco (UCSF). D&D Pharmatech provided drugs for research through its U.S. subsidiary Neuraly and supported discussions on the mechanism of action.
IDH mutant glioma is a brain tumor that abnormally accumulates D-2HG, a cancer-causing metabolite, due to mutations in the IDH1 or IDH2 genes. Even if it grows relatively slowly, it can recur or become more malignant in the long term. Vorasidenib is a targeted treatment approved by the U.S. Food and Drug Administration (FDA) in 2024 and delays tumor growth, but the company explains that there are limits to its effectiveness in directly killing cancer cells.
The researchers confirmed the expression of GLP-1 receptor in patients and mouse-derived tumor models and evaluated the effectiveness of the combination. GLP-1 receptor agonists increased nitric oxide production, and vorasidenib was shown to increase superoxide production in mitochondria while inhibiting mutant IDH enzymes. The explanation is that peroxynitrite, created by the reaction of the two substances, damaged the lipids and DNA of tumor cells and induced cell death. The proliferation inhibition effect that occurred when administered individually led to the death of cancer cells when administered together.
The combined effect was also observed in animal experiments. According to the company, when the two drugs were administered together to an IDH mutant glioma mouse model, a clear tumor shrinkage was observed compared to vorasidenib administered alone. The median overall survival time increased by about 60% from 22 days to 36 days, and statistical significance was confirmed (p<0.0001).
In this animal test, pegsebrenatide was evaluated at a molar-based dosage equivalent to about 1/14th of that of liraglutide. Antitumor effects were also observed through nasal administration. The company believes that in the future, it can further explore whether the treatment effect can be improved by securing systemic drug exposure more stably through subcutaneous injection.
D&D Pharmatech is collaborating with UCSF researchers to review the possibility of conducting an investigator-initiated clinical trial (IIT) targeting patients with IDH mutant glioma. If significant anti-tumor effects are confirmed in future clinical trials, the development of a rare brain cancer treatment will begin in earnest, and we plan to examine whether to utilize the FDA's expedited review and approval system.
Pegsebrenatide is a candidate material characterized by a long half-life of approximately 12 to 14 days and peptide stability in the brain. A phase 2 clinical trial for Parkinson's disease has been conducted, and a researcher-led phase 2 clinical trial targeting approximately 120 multiple sclerosis patients is currently underway led by researchers at Johns Hopkins University School of Medicine in the United States.
Seol-gi Lee, CEO of D&D Pharmatech, said, "This study is significant in that it confirmed the preclinical effect of cancer cell death and survival extension through the complementary action of pegsebrenatide and vorasidenib," and announced that he would review the possibility of follow-up clinical development with UCSF researchers and expand the treatment area to incurable rare brain cancer.
