A Phase 1/2a, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, and Efficacy of RZ-001 in Combination with Valganciclovir in Subjects with Glioblastoma

This is a Phase 1/2a, open-label study to evaluate the safety, tolerability, immunogenicity, and preliminary clinical activity of RZ-001 administered in combination with VGCV in subjects with hTERT-positive GBM.

开始日期2024-10-08

申办/合作机构

Rznomics Co., Ltd.

NCT05595473 / Active, not recruiting临床1/2期

A Phase 1/2a, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability and Efficacy of RZ-001 in Combination with Valganciclovir in Subjects with Hepatocellular Carcinoma

This is first in human study to evaluate the safety, tolerability, immunogenicity, and preliminary clinical activity of RZ-001 when given to subjects with human telomerase reverse transcriptase (hTERT)-positive HCC.

开始日期2022-07-29

申办/合作机构

Rznomics Co., Ltd.

NCT06676891 / Temporarily not availableN/A

Expanded Access to RZ-001 in Combination with Valganciclovir in the Treatment of Subjects with Glioblastoma

This small-size patient population expanded access program is to provide access to investigational product RZ-001 for up to around 4 patients with human telomerase reverse transcriptase(hTERT)-positive Glioblastoma (GBM) who are not eligible to participate in the RZ-001-201 clinical study or in any other study involving the use of RZ-001

开始日期-

申办/合作机构

Rznomics Co., Ltd.

100 项与 RZ-001 相关的临床结果

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100 项与 RZ-001 相关的转化医学

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100 项与 RZ-001 相关的专利（医药）

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项与 RZ-001 相关的文献（医药）

2022-07-30·The Plant cell1区 · 生物学

Progressive chromatin silencing of ABA biosynthesis genes permits seed germination in Arabidopsis

1区 · 生物学

Article

作者: Wu, Yufeng ; Yang, Deyue ; Chen, Min ; Zhu, Danling ; Qu, Li-Jia ; Kong, Xiangxiong ; Chen, Xi ; Wu, Zhe ; Du, Jiamu ; Zhao, Fengli

Abstract:

Seed germination represents a major developmental switch in plants that is vital to agriculture, but how this process is controlled at the chromatin level remains obscure. Here we demonstrate that successful germination in Arabidopsis thaliana requires a chromatin mechanism that progressively silences 9-CIS-EPOXYCAROTENOID DIOXYGENASE 6 (NCED6), which encodes a rate-limiting enzyme in abscisic acid (ABA) biosynthesis, through the cooperative action of the RNA-binding protein RZ-1 and the polycomb repressive complex 2 (PRC2). Simultaneous inactivation of RZ-1 and PRC2 blocked germination and synergistically derepressed NCEDs and hundreds of genes. At NCED6, in part by promoting H3 deacetylation and suppressing H3K4me3, RZ-1 facilitates transcriptional silencing and also an H3K27me3 accumulation process that occurs during seed germination and early seedling growth. Genome-wide analysis revealed that RZ-1 is preferentially required for transcriptional silencing of many PRC2 targets early during seed germination, when H3K27me3 is not yet established. We propose RZ-1 confers a novel silencing mechanism to compensate for and synergize with PRC2. Our work highlights the progressive chromatin silencing of ABA biosynthesis genes via the RNA-binding protein RZ-1 and PRC2 acting in synergy, a process that is vital for seed germination.

2020-03-01·Pathogens and disease4区 · 医学

Bacillus subtilis RZ001 improves intestinal integrity and alleviates colitis by inhibiting the Notch signalling pathway and activating ATOH-1

4区 · 医学

Article

作者: Li, Zhongyuan ; Zhang, Tengxun ; Gai, Sailun ; Wang, Nan ; Song, Yajian ; Luo, Xuegang ; Qi, Wei ; Geng, Meng ; Li, Yanru ; Zhang, Tongcun ; Guo, Congcong

ABSTRACT:

Intestinal mucosal barriers help the body resist many intestinal inflammatory diseases, such as inflammatory bowel disease (IBD). In this study, we identified a novel bacterium promoting the repair of intestinal mucosa and investigated the potential mechanisms underlying its activity. Culture supernatant of Bacillus subtilis RZ001 upregulated the expression of mucin 2 (MUC2) and tight junction (TJ) proteins in HT-29 cells in vitro. Oral administration of B. subtilis RZ001 may have significantly reduced symptoms such as the dextran sulfate sodium (DSS)-induced decrease in body weight, shortening of colon length and overproduction of proinflammatory factors. The number of goblet cells and levels of MUC2 and TJ proteins were significantly increased in adult mice fed with B. subtilis RZ001. B. subtilis RZ001 cells upregulated the levels of MUC2 in the intestinal organoids. Furthermore, culture supernatant of B. subtilis RZ001 could suppress the Notch signalling pathway and activate the expression of atonal homolog 1 (Atoh1). The transcription factor Atoh1 is required for intestinal secretory cell differentiation and activates transcription of MUC2 via binding to E-boxes on the MUC2 promoter. Taken together, B. subtilis strain RZ001 has the potential for treating IBD. The present study is helpful to elucidate the mechanisms of B. subtilis action.

2014-12-01·Phytotherapy research : PTR2区 · 医学

Anti‐inflammatory Effects of Ginsenosides Rg₅, Rz₁, and Rk₁: Inhibition of TNF‐α‐induced NF‐κB, COX‐2, and iNOS transcriptional expression

2区 · 医学

Article

作者: Lee, Sang Myung

In the course of this experiment on the anti‐inflammatory effect of ginsenosides, protopanaxdiol ginsenosides have shown inhibition activities in inflammatory responses: NF‐κB, COX‐2, and iNOS were induced by TNF‐α. The responses of this experiment were evaluated by NF‐κB‐luciferase assay and RT‐PCR experiment of COX‐2 and iNOS genes. The NF‐κB expressions were inhibited by ginsenosides Rd, Rg5, Rz1, and Rk1 in a dose‐dependent manner. The IC50 values were 3.47, 0.61, 0.63, and 0.75 μM, respectively. Particularly, ginsenosides Rg5, Rz1, and Rk1 as converted ginsenosides from primary protopanaxdiol ginsenosidess significantly inhibited COX‐2 and iNOS gene expression. These inhibition levels were similar to sulfasalazine as reference material. Copyright © 2014 John Wiley & Sons, Ltd.

项与 RZ-001 相关的新闻（医药）

2024-08-05

·PRNewswire

SK pharmteco and Rznomics Explore Collaboration for RNA-based Gene Therapy Development and Manufacturing

SEONGNAM, South Korea, Aug. 5, 2024 /PRNewswire/ -- SK pharmteco, a global contract development, manufacturing, and analytical testing organization serving both the small molecule and cell & gene therapy industry, and Rznomics Inc., a South Korea-based biopharmaceutical company specializing in the development of RNA-based gene therapeutics, have signed a memorandum of understanding (MOU) for a contract development and manufacturing partnership. When finalized, the multi-year partnership will establish a strategic collaboration between SK pharmteco and Rznomics to develop and commercialize multiple gene therapy products. SK pharmteco will provide technical expertise and resources, including the facilities and personnel, to enable a smooth transition from clinical to full-scale commercial manufacturing of Rznomics' innovative ribonucleic acid (RNA)-based biopharmaceuticals. "We are thrilled about the opportunity to partner with Rznomics on their groundbreaking initiatives," said Andy Fenny, Chief Commercial Officer of SK pharmteco. "By combining our significant expertise in gene therapy manufacturing with Rznomics' innovative RNA-based therapeutic approach, we believe this collaboration has the potential to deliver life-changing treatments to patients in need quickly." Seong-Wook Lee, President and Chief Executive Officer of Rznomics, commented: "This partnership will mark late-stage development and manufacturing of our gene therapy pipeline to prepare the path towards Phase II and later stage clinical trials and potential commercialization. We look forward to working closely with SK pharmteco." About SK pharmteco SK pharmteco is a global contract development and manufacturing organization (CDMO) with 13 offices and manufacturing facilities across the U.S., Europe, and Korea. The company partners with biopharmaceutical companies of all sizes to manufacture Active Pharmaceutical Ingredients (API) and intermediates, cell and gene therapy technologies, registered starting materials, and analytical services for the biopharmaceutical industry worldwide. SK pharmteco is a subsidiary of SK Inc. (KRX: 034730) (SK), the strategic investment company for SK Group, South Korea's second-largest conglomerate. About Rznomics Rznomics is a South Korea-based innovative RNA biopharmaceutical company, with vision to treat/conquer various human intractable diseases. Rznomics has developed and focused on several pipelines with RNA editing platform technologies of RZ-001 (Hepatocellular Carcinoma, Glioblastoma), RZ-003 (Alzheimer), RZ-004 (Retinitis Pigmentosa), RZ-005 (neurodegenerative disorder) and Circular RNA platform. For RZ-001, the lead pipeline, Rznomics has received Phase I/IIa IND approvals from the FDA for Hepatocellular Carcinoma and Glioblastoma in 2022 and 2023 each. In addition, FDA has granted Fast Track Designation for GBM in November 2023 and Orphan Drug Designation for HCC in January 2024. Early-phase trials have also commenced in Korea, upon IND approval for RZ-001 from the Ministry of Food and Drug Safety (MFDS). Rznomics has received IND approval for combination of RZ-001 and Immunotherapy from the MFDS as well, in December 2023. Contact: Keith Bowermaster, APR, CCMP Communications Consultant [email protected] Website: Jihye Yang Associate Manager [email protected] Website: SOURCE Rznomics Inc.

孤儿药快速通道临床申请临床研究基因疗法

2024-03-14

·FiercePharma

Charles River inks viral vector production pact for Navega's chronic pain gene therapy

Charles River will help bring NT-Z001 to the clinic by leveraging its off-the-shelf plasmid products, custom plasmid capabilities and adeno-associated virus (AAV) production. After charting multiple personalized medicine expansions in recent years, contract manufacturer Charles River Laboratories is back with another gene therapy pact—this time centered on an adeno-associated virus 9 (AAV9) candidate meant to serve as a non-opioid alternative for rare disease patients living with chronic pain. Charles River on Thursday announced a new accord with epigenetic gene therapy outfit Navega Therapeutics as part of the CDMO’s Cell and Gene Therapy Accelerator Program. The deal will grant Navega access to Charles River’s contract development and manufacturing capabilities and advisory services to produce the AAV gene therapy candidate NT-Z001 for phase 1 clinical trials, the companies said in a press release. Navega is positioning its gene therapy candidate to help treat chronic pain associated with rare diseases like small fiber neuropathy and primary erythromelalgia. The drug leverages Navega’s artificial intelligence-enabled zinc-finger gene-editing platform, the company explained. NT-Z001 specifically addresses a gain-of-function mutation in the Nav 1.7 gene, which is linked to inherited erythromelalgia, small fiber neuropathy and other chronic, debilitating pain disorders. Aside from pain tied to rare diseases, Navega figures its gene therapy could eventually address other pain indications, including neuropathic and inflammatory pain. Charles River, for its part, will help bring NT-Z001 to the clinic by leveraging its off-the-shelf plasmid products, custom plasmid capabilities and AAV production. Over the years, Charles River says it has significantly enhanced its cell and gene portfolio through a mix of acquisitions, capacity expansions and manufacturing platform launches, including eXpDNA for plasmids, nAAVigation for AAV and Lentivation for lentiviral vectors. Back in November 2022, the company debuted the expansion of its cell therapy manufacturing facility in Memphis, Tennessee. The plant reveal came just weeks after the CDMO opened a separate plasmid production facility in the U.K. Under the expansion, Charles River added nine processing suites to its 16 clean rooms at the Memphis site. The additions were designed to handle high-volume production—plus options for dual production lines—for late-stage clinical and commercial cell therapies, the company said at the time. Charles River also recently acquired a site in Rockville, Maryland, through its $350-million buyout of gene therapy CDMO Vigene Biosciences back in 2021. The site largely helps with the production of viral vectors, which have experienced supply constraints among advanced cell and gene therapies for several years. Elsewhere on the personalized medicines front, Charles River last year linked up with South Korea’s Rznomics to develop and crank out viral vectors for its partner’s experimental liver cancer gene therapy RZ-001. RZ-001 marks the first ribozyme-based RNA reprogramming approach to receive FDA authorization for evaluation in humans, the companies said last January.

基因疗法并购临床1期细胞疗法

2024-02-02

·PRNewswire

Rznomics Inc. Secures Orphan Drug Designation from FDA for RZ-001 in Hepatocellular Carcinoma

SEONGNAM, South Korea, Feb. 2, 2024 /PRNewswire/ -- Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, has received an Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for RZ-001, for the treatment of patients with Hepatocellular carcinoma (HCC). 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. Contact: [email protected] SOURCE Rznomics Inc.

孤儿药临床申请临床研究

100 项与 RZ-001 相关的药物交易

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