RIBOZYME AND OMICS
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SEONGNAM, South Korea, Oct. 25, 2022 /PRNewswire/ -- Rznomics Inc., a South Korea based biopharmaceutical company specialized in the development of RNA-based gene therapeutics, recently received Phase 1/2a IND approval from the U.S FDA in October 10th for its hepatocellular carcinoma (HCC) treatment called RZ-001 and thus has achieved an important milestone for the company and the RNA editing field. Being 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 HCC patients. Rznomics also received IND approval of RZ-001 from the South Korean Ministry of Food and Drug Safety this June and already initiated a phase 1/2a clinical trial in Korea. Therefore, U.S. FDA approval allows Rznomics to start an international clinical study in HCC patients treating them with RZ-001 and therapeutic RNA editing. 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 capable of both suppressing target RNA expression and simultaneously expressing a therapeutic RNA. Thus, no potentially antigenic proteins or cofactors are required. (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. (http://www.rznomics.com/pipeline/RZ-001.php). 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 least toxicities of RZ-001 in HCC patients with no extrahepatic metastasis. "The translation of the first trans-splicing-based RNA editing approach into an FDA-approved phase 1/2a clinical trial is an exciting achievement and a critical milestone for the RNA editing field. I am very excited about Rznomics' preclinical progress on ribozyme design and gene delivery optimization. The advances have allowed them to create and now translate a promising therapy, RZ-001, into the clinic. I and the entire editing field are eager to learn if RZ-001 and mRNA reprogramming is safe and able to combat hepatocellular carcinoma in patients. Rznomics is clearly a leader at bringing novel editing strategies to cancer patients that desperately need innovative, breakthrough therapies," said Dr. Bruce Sullenger, Joseph, and Dorothy Beard Professor of Surgery at Duke University. Dr. Sullenger is a scientific advisory board member of Rznomics and the initial pioneer developing approaches to therapeutically edit RNA and DNA using RNA guided endonucleases (RGENs) such as the group trans-splicing I ribozyme.. "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 the IND approval in both Korea and the United States. I am really grateful that RZ-001 earned the opportunity to potentially fulfill the unmet needs of HCC 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 Dr. Seong-Wook Lee, CEO and founder of Rznomics.In addition to the HCC, Rznomics is expanding the indication of RZ-001 to glioblastoma multiforme and planning to submit the IND this year. Also under development are ribozyme-based RNA editing treatments for Alzheimer's disease (RZ-003) and inherited retinal dystrophies, called Retinitis pigmentosa (RZ-004).
Rznomics announced on october 11th,2022 that it had received approval for phase 1 and 2 clinical trial (IND) of 'RZ-001' from the US Food and Drug Administration (FDA).The clinical trial plan was approved by the Ministry of Food and Drug Safety in June,2022 and is an extension of the ongoing domestic clinical trial.Rznomics has the technology to express the desired gene while removing the target ribonucleic acid (RNA) based on RNA trans-splicing ribozyme.RZ-001 targets telomerase (hTERT) RNA specifically expressed in cancer cells by delivering a ribonucleic acid substitution enzyme to an adenovirus vector.At the same time, it is a mechanism for expressing genes that induce anticancer activity.Rznomics is pushing to expand indications to other carcinomas, and is planning a clinical trial for malignant glioblastoma within this year.In addition to the anticancer drug pipeline, Rznomics is developing therapeutics in various fields using platform technology, such as Alzheimer's treatment, hereditary retinopathy, and Rett's syndrome.Seongwook Lee, CEO of Rznomics, said, "The pipelines under development are scheduled to begin clinical trials in korea and abroad sequentially, and we will do our best to provide new treatment opportunities to patients."
Rznomics
announced on the 16th that it won the most promising pipeline award in the gene
therapy category at the "Asia-Pacific Cell & Gene Therapy Excellence
Awards" (ACGTEA) of the "Cell & Gene Therapy World Asia
2022" (CGTWA 2022) held in Singapore.
CGTWA
is an event to share representative technologies of cell and gene therapy.
At
the conference which is followed after the award, the "next-generation
cell gene therapy" session was announced.
In
the presentation, Rznomics explained the current status of candidate substances
(pipelines) including trans-splicing ribozyme based gene therapy platform
technology and liver cancer therapy currently undergoing clinical trials. As
a company with first-in-class platform technology, it presented technological
innovation and vision.
Rznomics
plans to apply for clinical trials for glioblastoma patients in the United
States and Korea in the first quarter of next year. In the second half of next
year, the U.S. is also planning to perform clinical trials on hereditary
retinitis pigmentosa.
Seong-wook,
Lee, CEO of Rznomics, said, "This award will be a great help to executives
and employees who have a desire to develop new drugs and those who supported
Rznomics," adding, "We will do our best to achieve better
results."
Rznomics announced on the 9th that it has applied to
the U.S. Food and Drug Administration (FDA) for a phase 1/2a clinical trial of
the hepatocellular cancer therapy "RZ-001".
It
is an extension of the domestic clinical trial that was approved by the
Ministry of Food and Drug Safety in June and is being submitted for the
originally planned multinational clinical trial.
Based
on RNA trans-splicing ribozyme, Rznomics is developing a technology that
removes target RNA and simultaneously expresses the desired gene.
RZ-001
is a mechanism that targets the telomerase (hTER) RNA that is specifically
expressed by cancer cells by transferring ribonucleic acid substitution enzymes
through the adenovirus vector and expresses genes that induce anticancer
action.
Rznomics
is also pushing to expand indications to other cancer species, and especially plans
to perform clinical trials on malignant glioblastoma within this year.
In
addition to the anticancer drug pipeline, it is developing therapy in
various fields using platform technologies such as Alzheimer's therapies,
hereditary retinopathy, and Rett’s syndrome.
Genetic
retinal pigmentosa was registered with the Korean Intellectual Property Office
in May, followed by a notification of the registration decision from the U.S. Patent
Office in August to prove its technological progress, the company added.
Seong-wook,
Lee, CEO of Rznomics, said, "The pipelines under development will be
launched sequentially at home and abroad, and we will do our best to provide
patients with new therapy opportunities."
CEVEC’s license partner RZNOMICS Inc. receives approval to initiate clinical development of CAP® Ad Technology-produced gene therapy vector in liver cancer patientsRZNOMICS uses CEVEC’s CAP® Ad viral vector manufacturing technology for manufacturing gene therapy vectors targeting various cancer indicationsSouth Korean Ministry of Food and Drug Safety granted IND approval for a clinical phase 1/2a trial to evaluate safety and efficacy of RZNOMICS lead gene therapy RZ001 for the treatment of primary liver cancerAnother important milestone has been reached for CEVEC’s unique CAP® cell line which enables by design the efficient production of high-quality, RCA-free adenoviral vectorsCologne, Germany, July 13, 2022CEVEC Pharmaceuticals GmbH (CEVEC) today announced that an important milestone in the partnership with RZNOMICS, Inc. (RZNOMICS) was achieved when the South Korean Ministry of Food and Drug Safety granted IND (Investigational New Drug) approval to initiate a phase 1/2a clinical trial with RZNOMICS’ lead candidate RZ001. RZ001, a gene therapy based on the company’s proprietary trans-splicing ribozyme technology and being developed for the treatment of primary liver cancer, uses CEVEC’s CAP® Ad Technology to manufacture RCA-free adenoviral vectors for the efficient and safe drug delivery to the target cells. With this regulatory clearance, RZNOMICS plans to submit an IND to the U.S. Food and Drug Administration (FDA) in the second half of this year.“We are delighted to see RZNOMICS advance its lead compound, a gene therapy produced using our CAP® Ad Technology, into clinical development,” said Dr. Nicole Faust, CEO of CEVEC. “By providing a unique technology that enables the manufacturing of safe adenoviral vectors by eliminating the generation of replication competent adenovirus (RCA), we help our partners to address one of the major challenges in adenovirus-based gene therapy and vaccine production. We look forward to continuing the work with RZNOMICS and supporting them through clinical development and further onto the market.”“This is a monumental achievement of administering a therapeutic substance using ribonucleic acid splicing enzyme technology to patients with primary liver cancer for the first time in the world”, said Seong-Wook Lee, Ph.D., CEO of RZNOMICS. “The advantages of the CAP® Ad Technology in terms of safety and scale up convinced us to select it as the technology to produce our gene therapy candidate based on adenoviral vector for the clinical purporse”, he added.In 2020, CEVEC and RZNOMICS signed a license agreement for the use of CEVEC’s CAP® Ad Technology for manufacturing of adenoviral vectors in combination with RZNOMICS’ proprietary development portfolio of gene therapies targeting various cancer indications.About CAP® Ad TechnologyThe CAP® Ad Technology is an innovative technology platform developed by CEVEC for the scalable production of RCA-free adenoviral vectors for gene therapy applications and vaccines.Recombinant adenoviral vectors are among the most efficient vectors for gene therapy purposes and have become the vehicle of choice in many human gene therapies. Today, many cell lines used for production of adenoviral vectors generate certain levels of replication-competent adenovirus (RCA). The presence of RCA in adenoviral vector preparations which are intended for use in humans is increasingly considered to be a potential risk, especially for immuno-compromised patients. The CAP® cell line is specifically designed to avoid the production of RCA.CEVEC’s CAP® cell line is based on an engineered human suspension cell line of non-tumor origin, derived from human amniocytes. CAP® cells can be grown in all formats and all sizes of bioreactors, providing a robust, fully scalable production platform for the manufacturing of adenoviral vectors from research grade and smaller amounts up to industrial volumes. The CAP® cell line has been fully documented and reviewed by regulatory authorities. Since 2016, a Biologics Master File has been available for reference with the U.S. FDA. GMP Master Cell Banks are available and ready for licensing.About CEVECCEVEC is a leading provider of high-performance cell technology for the manufacturing of advanced biotherapeutics.With the ELEVECTA® Technology, CEVEC offers a unique solution for large-scale production of AAV vectors using helper virus-free inducible producer cell lines with all necessary components stably integrated into the cell. The technology is based on suspension cells and does not require any expensive transfection reagents nor cGMP plasmids. CEVEC’s CAP® Ad Technology is the ideal production platform for RCA-free adenoviral vectors. Based on human suspension cells, it allows for a robust manufacturing process, easy scale-up from research grade to industrial volumes and thus opens the way for various applications, from gene therapy to vaccine production.About Rznomics:Rznomics is a biopharmaceutical company founded in 2017 dedicated to the development of gene therapies for cancers, degenerative diseases, and genetic diseases based on cutting-edge RNA technology. Core platform technology of Rznomics is based on RNA replacement enzyme called ‘trans–splicing ribozyme’, which can edit target RNAs through simultaneous destruction and repair (and/or reprograming) to yield the desired therapeutic RNAs, thus selectively inducing therapeutic gene activity in cells expressing the target RNAs. Rznomics has developed and optimized the ribozymes to be applied as therapeutics for intractable human disease by developing them to have high target specificity and efficacy, target accuracy, and minimal off-target ability. Rznomics has established pipelines targeting indications with high unmet medical demand for which the unique properties of the ribozymes can be the most competitive. The leading candidate is treatment for hepatocellular carcinoma, and treatments for glioblastoma, Alzheimer’s disease and hereditary retinal dystrophy are also under development. For more information, please visit www.rznomics.com.
Rznomics
announced on the 21st that it has received approval from the Ministry of Food
and Drug Safety for phase 1 and 2a clinical trials of "RZ-001", which
is being developed as a primary liver cancer treatment.
Phase
1 for safety verification and phase 2a for effectiveness search were designed
to be implemented in one clinical trial.
Rznomics
has a platform technology that can remove targeted RNA using RNA trans-splicing
ribozyme while expressing the desired gene.
This
platform was also applied to RZ-001. It is explained that it targets telomerase
(hTER) RNA, which is specifically expressed in cancer cells, to secure safety
and at the same time to express genes that induce anticancer action. In this
process, it is said to induce immune cells in the body, causing triple
anticancer effects.
Rznomics
plans to perform multinational clinical trials after obtaining approval from
the U.S. Food and Drug Administration (FDA) for the same clinical design in the
second half of this year. In Korea, Samsung Medical Center, Seoul National
University Hospital, Severance Hospital, Seoul St. Mary's Hospital and
Kyungpook National University Hospital will participate as clinical trial
institutions.
Seong-wook,
Lee, CEO of Rznomics, said, "It is a monumental task to administer a treatment
substance using RNA trans-splicing ribozyme technology to primary liver cancer
patients for the first time," adding, "We will do our best to provide
new treatment opportunities to patients in need of anti-cancer treatment."
Rznomics
is also promoting the expansion of indications to various cancer types. In the
case of malignant glioblastoma, it is planned to enter the clinical stage
within this year.
Rznomics Inc. (https://www.cortellis.com/intelligence/qsearch/rznomics) recently secured ₩37.2 billion
(US$30 million) from private investors and the Korean government in a series C financing round. “The
$30 million series C proceeds will be used for the phase I/IIa clinical trial of RZ-001 (https://www.cortellis.com/intelligence/qsearch/RZ-001), and the additional R&D costs for candidates RZ-004
(https://www.cortellis.com/intelligence/qsearch/RZ-004) and RZ-003 (https://www.cortellis.com/intelligence/qsearch/RZ-003),” Rznomics CEO Seong-wook Lee told BioWorld.
RZ-001, Rznomics’ lead candidate, is an investigational RNA replacement enzyme vector-based cancer
therapy to treat hepatocellular carcinoma (HCC). A phase I/IIa trial of the candidate is planned for initiation in the second half of 2022. “It will be a dose escalation/expansion study, to be held at major study
sites in South Korea including the Samsung Medical Center. The clinical trial’s expected milestone dates
are to be determined,” said Lee. He hailed the financing as one of great value in “the depressed bio-market atmosphere.”
RZ-004 is a preclinical gene therapy candidate targeting retinitis pigmentosa. The IND for that indication
is to be submitted to FDA in the first half of 2023. RZ-003 is the company’s adeno-associated virus (AAV)
delivered candidate, intended for the potential treatment of Alzheimer’s disease.
Also in Rznomics’ pipeline is in RZ-002, another adenovirus candidate for glioblastoma. An IND submission for the telomerase reverse transcriptase targeting candidate planned for this year. “Rznomics is planning to submit the IND to the FDA for RZ-004 in 2023 and for RZ-001 with the indication
of glioblastoma in 2023,” said Lee.
The most recent financing brings Rznomics’ cumulative investment total to date to ₩60.9 billion. Investors in the RNA-focused biopharma include the Korea Development Bank, AON investment, Partners
Investment, IBK Capital Corp, Quad Ventures, SBI Investment Co. Ltd., Shinhan Venture Investment Co.
Ltd., and UTC Investment Co. Ltd. “The investment was made by the consideration of specialty and capabilities of trans-splicing ribozyme
in RNA based treatments, competitive pipelines, and the high level of R&D data,” said Byung-kyu Ahn,
the director of AON Investment, a new participant that joined in the series C. “After the COVID-19 pandemic, the needs and expectations of gene therapy have increased. I believed
Rznomics showed capabilities of satisfying the global needs. In contrast to the CRISPR-Cas9 system that
causes permanent gene editing, trans-splicing ribozyme technology induces gene editing at the RNA
level,” said Junsoo Kim, a managing director in Partners Investment.
Partners investment has been onboard with Rznomics from its series A to C financing rounds. Government funding, IPO In addition, the company's work has since been recognized by the South Korean government as several
government funding projects, including the development of RZ-004 as a 'national new drug development project'. The recognitions won it a separate cumulative ₩8 billion in research funding. “Overall, the environment for the development of gene therapy in South Korea is pretty active and
bright. We have received proper support and reviews from the Ministry of Food and Drug Safety and
with that, also have plans to develop our pipelines globally,” he added. That’s not all the financing news that Rznomics has for now. The company is currently busy preparing the
evaluation of its technology to be included as a technology specially listed company. It is also exploring
the potential for an IPO as a technology specially listed company, possibly for the second half of 2023.
The last time (https://www.bioworld.com/articles/499139-rznomics-on-track-for-adenoviruses-development-plan) BioWorld spoke to the company in 2020, it was using Cologne, Germany based-Cevec Pharmaceuticals GmbH’s technology to manufacture adenoviruses. “The contract has been signed and we
have completed the GMP production for RZ-001,” said Lee. Rznomics is heavily invested in its trans-splicing ribozyme platform, technology designed to remove disease-causing target RNA and trans-ligates, as well as opportunities to out-license the technology to global
partners.<source>BioWorld
Rznomics, raised KRW 37.2 B in series
C round
Rznomics, a new drug developer for RNA-based gene
therapy, announced on the 7th that it has completed attracting KRW 37.2 billion
in Series C round.
In this round, Korea Development Bank, AON Investment,
Partners Investment, IBK Capital, Quad Ventures, SBI Investment, Shinhan
Venture Investment, and UTC Investment participated as investors.
As a result, Rznomics achieved a cumulative total of KRW
60.9 billion, including KRW 23.7 billion in series A and B, and received about KRW
8 billion in government-funded research funds through national new drug
development projects.
Rznomics has an innovative platform technology so called
Trans-splicing ribozyme, and represents a mechanism to remove disease-causing
target RNA and express therapeutic RNA in its place.
Using this, innovative new drugs are being developed
for liver cancer, glioblastoma, Alzheimer's, and hereditary retinal
pigmentation.
Furthermore, it has secured its own circular RNA
structure platform technology that can be applied to various fields such as
treatments and vaccines.
In the case of liver cancer treatments, which are the
most advanced in the new drug pipeline, clinical trials (phase 1/2) are
scheduled in Korea and the United States from the second half of this year, and
a clinical trial plan for glioblastoma is also planned within this year.
In the first half of next year, a clinical trial plan
for Retinitis pigmentationosa, a rare eye disease, will also be submitted to
the U.S. FDA.
In addition, it is planning to take a technology
evaluation for Special Listing of Technology Growth in the first half of next
year and is pushing for an IPO with the goal of the second half of next year.
Seong-wook, Lee, CEO of Rznomics, said, "It is a
great help because it seems to have been recognized for its potential and value
despite the stagnant bio-market atmosphere, and we will accelerate research and
development even more." "We are actively discussing with leading
multinational pharmaceutical companies for license-out, so we expect to deliver
good news soon."
Regarding the reason for the decision to participate
in this investment since Series A, Kim Joon-soo, senior team leader of Partners
Investment, said, "The need and expectations for gene therapy are rising
after COVID19 pandemic, and in particular, Rznomics has unrivaled global
competitiveness."
RNA trans-splicing technology implements RNA-level
correction unlike gene scissors that cause permanent genetic modification, and
operates as an enzyme's own mechanism without needing help from external
proteins for correction function, allowing for permanent development and
commercialization of new drugs.
In other words, we decided to invest not only because
we could fundamentally solve the medical unmet demand of genetic and
intractable diseases, but also because we could expect the scalability and
profitability of the business," he said.
Byung-kyu, Ahn, director of AON Investment, who
participated in this investment with a large scale as a new Venture Capital,
also said, "We decided to invest this time by comprehensively considering
the mechanical differentiation of R&D technology owned by Rznomics in the
RNA therapy area, pipelines that can maximize it, and R&D data at the
global level."
Rznomics,
trans-splicing ribozyme based gene therapy technology platform company, announced
on the 12th that their innovative new drug treatment, which is being developed
for hereditary retinal pigmentation, was selected as a support project for the
National New Drug Development Project's first "New Drug R&D Ecosystem
Construction Research" in 2022.The
national new drug development project is a pan-ministerial national R&D
project, which is promoted by the Ministry of Science and ICT, the Ministry of
Trade, Industry and Welfare, and has been supporting the whole cycle of new
drug development since 2021 with the goal of strengthening global
competitiveness of the national pharmaceutical and bio industries.Rznomics'
selected research on building a national new R&D ecosystem is a task to
support candidate materials and non-clinical stages, and this selection will
receive a total of KRW 2 billion in national research funds for 22 months with
the goal of non-clinical research and IND approval.Retinal
pigmentation is a blindness disease that occurs in one out of every 4,000 to
5,000 people worldwide and loses central vision due to abnormal photoreceptor
cells distributed in the retina.Up
to now, there is no fundamental treatment method, and it has relied on some
adjuvant treatments that prevent vision from being damaged by ultraviolet rays
or slow vision loss by taking nutritional supplements.The
cause of retinal pigmentation is a defect in the genes involved in the
mechanism of converting light into electrical signals in visual cells.Among
several gene mutations, mutations in the RHO gene are known to be the most
common form of mutations in the disease, accounting for 20 to 30% of autosomal
dominant retinal pigmentation.The
progress rapidity of vision damage depends on individual, but it usually starts
with night blindness, gradually narrowing the field of vision, and losing the
central field of vision, leading to complete blindness.The
treatment under development by Rznomics is an RNA-based gene therapy that is
being developed for a single administration, and it is expected that the
disease can be fundamentally treated by replacing the mutant RHO gene with the
normal RHO gene using "Trans-splicing ribozyme" technology, which
removes and corrects the mutant gene.Dr.
Ji-hyun, Kim who was selected as the research director of the project, said,
"Rznomics' platform technology, which has accumulated technology for a long
period of time, has been recognized for its excellence, and we will do our best
to approve IND with the goal of clinical progress."Seong-wook,
Lee, CEO of Rznomics, said, "This is the second national new drug project
since the development of Rett’s syndrome treatment was selected as a national
new drug project at the end of last year, and it is believed to be a good
example of new drug development as a bio-venture in Korea."