FDA approval for the Rznomics glioblastoma treatment trial


Rznomics Inc., a South Korea-based biopharmaceutical company specializing in the development of RNA-based gene therapies, has received IND phase 1/2a approval from the US FDA for the treatment of glioblastoma multiforme (GBM).

RZ-001 initially obtained IND approval for hepatocellular carcinoma (HCC), but Rznomics has also found pre-clinical efficacy in a GBM model and submitted IND to GBM.

As the first US FDA-approved ribozyme-based RNA reprogramming approach to be evaluated in patients, RZ-001, a gene therapy approach that utilizes the company’s proprietary trans-splicing ribozyme-based RNA reprogramming and editing technology, is a replication-incompetent adenoviral vector expressing targeting ribozymes. hTERT with some additional MoAs to treat GBM patients.

The trans-splitting ribozyme originates from self-splitting group I Tetrahymena introns, which recognize and reprogram the target RNA into the therapeutic transcript of interest.

Unique features of Rznomics

The ribozyme-based RNA editing technology developed by Rznomics has unique features, which the company says set it apart from other nucleic acid-based editing approaches. A single RNA molecule is catalytically capable of suppressing target RNA expression and simultaneously expressing therapeutic RNA. Thus, no potentially antigenic proteins or cofactors are required. In addition, safety can be enhanced by selectively inducing therapeutic RNA expression only in cells/tissues where the target gene is expressed.

Therapeutic gene expression can be regulated in proportion to the level of endogenous cellular target RNA. In addition, editing occurs at the RNA level, not the genomic level, eliminating concerns about genomic toxicity and lasting genomic changes.

Indications with multiple mutation sites scattered throughout the target RNA can be edited with a single RNA designed to react upstream of all mutations and by substituting and editing most of the RNA. Additional security can be provided by building control mechanisms into the ribozyme itself, without the need to modulate intrinsic cellular mechanisms or external proteins.

RZ-001 exerts effective anti-GBM activity by selectively suppressing hTERT expression in cancer cells, which overexpress hTERT, and by concurrently inducing a cytotoxic effect by trans-ligating the HSVtk coding sequence into the reprogrammed hTERT mRNA.

These edits induce infiltration of immune cells into GBM tumors and inhibit angiogenesis in tumor tissue in preclinical animal models.

Rznomics expands the pipeline

The 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 lowest toxicity of RZ-001 in recurrent GBM patients without extracranial metastases.

“It is a monumental Rznomics achievement that RZ-001, the first ribozyme trans-splicing therapy on our therapeutic frontier, has successfully received another IND approval in the United States with an indication for GBM. I am so grateful that RZ-001 has had the opportunity to meet the unmet needs of GBM patients. Through the advanced development phase, I hope that Rznomics will be able to provide more new therapeutic options to patients suffering from intractable diseases. Rznomics will continue to broaden our channel by targeting indications with severely unmet medical needs where the unique characteristics of our platform technology can be applied most competitively,” said Seong-Wook Lee, CEO and founder of Rznomics.

In addition to HCC & GBM, Rznomics is developing a ribozyme-based RNA editing treatment for Alzheimer’s disease (RZ-003) and an inherited retinal dystrophy, called retinitis pigmentosa (RZ-004).

Earlier this year, CANbridge Pharmaceuticals reported a 67% five-year survival rate in its drug candidate study, CAN008, in addition to standard chemoradiotherapy treatment.

And last year, Northwest Biotherapeutics, which developed a personalized DCVax immune therapy for solid tumor cancer, reported positive results with newly diagnosed and recurrent glioblastoma patients.


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