▶ UCSF research team identifies powerful anti-tumor synergy between Peglebenatide (NLY01) and targeted anticancer drug 'vorasidenib' in IDH-mutant brain tumors.
▶ Moving beyond the growth-suppression limits of conventional targeted therapies to induce direct cancer cell death, preclinical results show tumor reduction and extended survival.
▶ Expansion of therapeutic applications and drug value into refractory, rare brain cancers following neurological indications such as Parkinson's disease and multiple sclerosis.
DnD Pharmatech’s (347850) novel drug candidate peglebenatide (NLY01) has demonstrated the ability to induce cancer cell death and prolong survival in IDH-mutant gliomas when combined with a targeted anticancer drug in preclinical studies. The findings suggest the potential of the drug—originally developed for neurological disorders—to treat brain tumors, prompting the company to consider follow-up clinical trials.
DnD Pharmatech announced on the 23rd that the results of the combination study evaluating peglebenatide, a long-acting GLP-1 receptor agonist, and the targeted therapy vorasidenib were published on the life sciences preprint platform bioRxiv.
The study was led by Professor John De Groot of the Department of Neurological Surgery and Professor Pavithra Viswanathan of the Department of Radiology and Biomedical Imaging at the University of California, San Francisco (UCSF). DnD Pharmatech provided the investigational drugs and supported mechanism-of-action discussions through its U.S. subsidiary, Neuraly.
IDH-mutant glioma is a brain tumor characterized by the abnormal accumulation of D-2HG, an oncometabolite, caused by mutations in the IDH1 or IDH2 genes. Although relatively slow-growing, these tumors carry a high risk of long-term recurrence and malignant progression. Vorasidenib, approved by the U.S. Food and Drug Administration (FDA) in 2024, is a targeted therapy that delays tumor growth, though the company noted its limitations in directly killing cancer cells.
After confirming GLP-1 receptor expression in patient- and mouse-derived tumor models, the researchers evaluated the combination's efficacy. The findings showed that the GLP-1 receptor agonist increases nitric oxide production while vorasidenib inhibits mutant IDH enzymes and increases mitochondrial superoxide generation. The resulting peroxynitrite formed by the interaction of the two agents damages tumor cell lipids and DNA, thereby inducing apoptosis. While monotherapies showed only growth-suppressive effects, the combination achieved direct cancer cell death.
The combination benefit was also observed in animal models. According to the company, co-administering the two drugs to IDH-mutant glioma mouse models resulted in marked tumor reduction compared to vorasidenib monotherapy. The median overall survival increased by approximately 60%, from 22 days to 36 days, with statistical significance (p<0.0001).
In these animal tests, peglebenatide was evaluated at a molar dosage roughly 1/14th that of liraglutide. Anti-tumor efficacy was also observed via nasal administration. The company noted that future exploration could determine whether systemic drug exposure via subcutaneous injection can further optimize therapeutic efficacy.
DnD Pharmatech is discussing the feasibility of an investigator-initiated trial (IIT) for patients with IDH-mutant gliomas in collaboration with the UCSF research team. Should significant anti-tumor efficacy be confirmed in future clinical trials, the company plans to accelerate the development of treatments for rare brain cancers and explore the use of FDA expedited review and accelerated approval pathways.
Peglebenatide is characterized by a long half-life of approximately 12 to 14 days and high peptide stability in the brain. Having previously completed Phase 2 clinical trials for Parkinson's disease, it is currently undergoing an investigator-initiated Phase 2 clinical trial involving approximately 120 multiple sclerosis patients, led by researchers at Johns Hopkins University School of Medicine.
"This study is highly significant as it demonstrates in preclinical models that the complementary mechanisms of peglebenatide and vorasidenib can successfully induce cancer cell death and extend survival," said Seul-ki Lee, CEO of DnD Pharmatech. He added that the company will review subsequent clinical development with the UCSF research team and expand its therapeutic footprint into refractory, rare brain cancers.
