The ODD granted to RZ-001 in HCC may allow it to receive 7 years of marketing exclusivity upon product approval, exemption from user fee and tax credits. This also may provide access to specialized regulatory assistance from FDA's Office of Orphan Products Development (OOPD).

The 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. Ribozyme-based RNA editing technology developed by Rznomics has unique features, differentiating it from other nucleic acid-based editing approaches, as follows: (1) A single RNA molecule is catalytically capable of both suppressing target RNA expression and simultaneously expressing a therapeutic RNA. Thus, this dual activity potentially requires no extra proteins or cofactors. (2) Safety can be improved by selectively inducing therapeutic RNA expression only in cells/tissues where the target gene is expressed. (3) Therapeutic gene expression can be regulated proportionally to endogenous cellular target RNA levels. (4) Editing occurs at the RNA level, not the genomic level, thus eliminating concerns about genomic toxicity and eternal genome changes. (5) Indications 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. (6) Additional safety can be conferred by building control mechanisms into the ribozyme itself, without the need to modulate intrinsic cellular mechanisms or external proteins. 

More specifically, RZ-001 engenders effective anti-HCC activity by suppressing hTERT expression selectively in cancer cells, which over-express hTERT, and simultaneously inducing a cytotoxic effect by trans ligating an HSVtk-encoding sequence into the reprogrammed hTERT mRNA. Moreover, the result of such editing efficiently induces immune cell infiltrations into HCC tumors in preclinical animal models.

"This FDA Orphan Drug Designation further underlines the potential of our pipeline to expeditiously address the current unmet medical needs of patients with Hepatocellular Carcinoma," said Seong-Wook Lee, CEO and founder of Rznomics.

Rznomics received Phase I/IIa IND approvals for RZ-001 in Hepatocellular Carcinoma (HCC) both from the FDA and the South Korean Ministry of Food and Drug Safety (MFDS), and this will be a dose escalation/expansion study to investigate the safety, tolerability, and efficacy of RZ-001 in HCC patients with no extrahepatic metastasis. In addition to HCC, Rznomics received Phase I/IIa IND approvals for RZ-001 GBM (Both in Korea and the U.S.) and Fast Track.

Most recently, Rznomics has entered into an HCC clinical collaboration agreement with F.Hoffmann-La Roche Ltd (Roche) to study RZ-001, in combination with Roche's atezolizumab.