Rznomics Inc., a South Korea based biopharmaceutical company specializing in the development of RNA-based gene therapeutics, has received phase 1/2a IND approval from the U.S. FDA for its glioblastoma multiforme (GBM) treatment.\n\n\n\nRZ-001 initially obtained IND approval for hepatocellular carcinoma (HCC), but Rznomics also found pre-clinical efficacy in GBM models and submitted the IND for the GBM. \n\n\n\nAs the first U.S. FDA-approved ribozyme-based RNA reprogramming approach to be evaluated in patients, RZ-001, a gene therapy approach utilizing the company's proprietary trans-splicing ribozyme-based RNA reprogramming and editing technology, is a replication-incompetent adenoviral vector that expresses an hTERT targeting ribozyme with multiple additional MoA to treat GBM patients.\n\n\n\nThe trans-splicing ribozyme is derived from the self-splicing Tetrahymena group I intron, which both recognizes and reprograms the target RNA into the therapeutic transcript of interest. \n\n\n\nRznomics' unique features\n\n\n\nRibozyme-based RNA editing technology developed by Rznomics has unique features, which the company said differentiate it from other nucleic acid-based editing approaches. A single RNA molecule is catalytically capable of both suppressing target RNA expression and simultaneously expressing a therapeutic RNA. Thus, no potentially antigenic proteins or cofactors are required. Also, safety can be improved by selectively inducing therapeutic RNA expression only in cells/tissues where the target gene is expressed. \n\n\n\nTherapeutic gene expression can be regulated proportionally to endogenous cellular target RNA levels. Also, editing occurs at the RNA level, not the genomic level, thus eliminating concerns about genomic toxicity and eternal genome changes. \n\n\n\nIndications with multiple mutation sites scattered throughout a target RNA can be edited with a single RNA designed to react upstream of all mutations and by replacing and editing large stretches of RNA. Additional safety can be conferred by building control mechanisms into the ribozyme itself, without the need to modulate intrinsic cellular mechanisms or external proteins. \n\n\n\nRZ-001 engenders effective anti-GBM activity by suppressing hTERT expression selectively in cancer cells, which over-express hTERT, and by simultaneously inducing a cytotoxic effect by trans ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. \n\n\n\nThe result of such editing induces immune cell infiltrations into GBM tumors and hampers angiogenesis in the tumor tissues in preclinical animal models. \n\n\n\nRznomics expanding pipeline\n\n\n\nThe phase 1/2a clinical trial will be a dose escalation/expansion study to assess the safety and tolerability of RZ-001 and to determine the most effective dose with the least toxicities of RZ-001 in recurrent GBM patients without extracranial metastases. \n\n\n\n"It's a monumental achievement of Rznomics that RZ-001, the first trans-splicing ribozyme therapy at the front of our therapeutic pipeline, has successfully received another IND approval in the United States with the indication for the GBM. I am really grateful that RZ-001 earned the opportunity to potentially fulfill the unmet needs of GBM patients. Through the advanced development phase, I hope Rznomics can provide more new therapeutic options to patients suffering from intractable diseases. Rznomics will further expand our pipeline by targeting indications with highly unmet medical needs for which the unique characteristics of our platform technology may be the most competitively applied," said Seong-Wook Lee, CEO and founder of Rznomics.\n\n\n\nIn addition to the HCC & GBM, Rznomics is developing ribozyme-based RNA editing treatments for Alzheimer's disease (RZ-003) and inherited retinal dystrophies, called retinitis pigmentosa (RZ-004). \n\n\n\nEarlier this year, CANbridge Pharmaceuticals reported a 67% five-year survival rate in a study of its drug candidate, CAN008, alongside standard chemoradiotherapy treatment.\n\n\n\nAnd last year, Northwest Biotherapeutics, which is developing DCVax personalized immune therapies for solid tumor cancers, reported positive results with both newly-diagnosed and recurrent glioblastoma patients.