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Rznomics Develops the World’s First RNA Editing Therapy: “TSR will be the Standard Treatment”
Rznomics develops
anticancer drug and rare disease therapies using the world’s first RNA editing
platform, Trans-Splicing Ribozyme(TSR). Through a special track, the company aims
to be listed on KOSDAQ market as early as this year, or next year at the latest.
Seong-Wook Lee, CEO of Rznomics said, “TSR has a potential for expanding to a package-deal
with asset and platform technology.” He added, “We will sign a licensing-out contract
soon, and apply for a technology evaluation.”A Pioneer of
RNA Editing Technology
In 2017, Dr. Lee
established Rznomics Inc., after 20 years of TSR research. Since 1994, he began
researching TSR during his postdoctoral fellowship at Duke University Medical
Center, one of the institutions initially developed and published TSR
technology. At that time, he focused on RNA-based autoimmune disease therapeutics
and gene therapy, which was a novel approach. The work was reported on the cover
of Nature Biotechnology, January 1997. After then, he returned to Korea
and joined Dankook University as a professor.
Dr. Lee continued
developing TSR in Korea but it was a challenge, because many scientists shifted
their path to RNA interference (RNAi) research, which was newly discovered in
the early 2000s.
“When I
developed TSR at the first time, it was not enough to verify its specificity
and efficacy. Moreover, in vivo delivery systems required more study. In the
late 2000s, I was finally able to achieve tumor-specific treatment data with
animal models. Gene therapy using virus vector as delivery system was tested in
the market, so it accelerated TSR development.”
The R&D
project was on track as Rznomics was established in 2017. Dr. Lee emphasized, “Not
only the platform, but we will make a meaningful deal with our own asset based
TSR technology. We’ve already organized the development system and clinical/pre-clinical
Pipelines.”
Safer than
any other Gene Editing
TSR technology
is specifically designed to avoid direct DNA editing. It removes targeted RNA
and then replaces it with therapeutic RNA; it demonstrates the possibility of dual
function with a single substance. It also can be programmed to deliver customized
drugs to the target gene.
Depending on the
indication, it utilizes proper viral vectors. Adenovirus is used for temporary
treatment including cancer therapy, and adeno-associated virus (AAV) is used
for one-shot genetic cure.
TSR technology
is frequently compared with CRISPR gene editing, one of the promising platforms
in the gene therapy field. Although CRISPR therapy provides the correction of
abnormal genes, it causes concerns that might be functioned at off-target permanently.
At present, there is no approved in vivo gene therapy yet.
Dr. Lee
explained that TSR shows off-target effects rarely. “If we try to edit a specific
part of RNA A, but RNA B works normally and will be produced in the cell. Even
if TSR inadvertently targets RNA B, but any off-target effects are transient
and limited.”
RNAi
therapeutics inhibit target RNA for treatment, but there is a limited option
and the current delivery system can reach liver cells only. For that reason,
most global RNAi pipelines target liver-related diseases and they have limited
potential to expand the target indication to other oncology.
Rznomic’s lead pipeline
RZ-001 is in Phase 1b/2a trials for hepatocellular carcinoma (HCC) in the U.S.
and Korea, and in Phase 1/2a for glioblastoma multiforme (GBM). The U.S. FDA
has granted RZ-001 Orphan Drug Designation (ODD) and Fast Track program for
both indications. Moreover, RZ-001 received approval for an Expanded Access
Program (EAP) in GBM, allowing medication prior to official approval to the patients
who have no approved treatment.
Rznomics plans
to enter a combination clinical trial with immunotherapy and already contracted
to Roche and Celltrion for receiving Tecentriq and Vegzelma (Avastin
biosimilar) for free of charge. Tecentriq and Avastin are the FDA-approved first-line
therapy for HCC.
Dr. Lee noted,
“In preclinical studies, RZ-001 improved biomarkers associated with
immunotherapy. The result encouraged our partners to pay attention to the potential
of RZ-001.”
The company is
accelerating the development of rare disease therapeutics with TSR. Dr. Lee
said, “Not only the cancer therapy, but TSR is also competitive for rare and
incurable diseases treatment. It comes from the unique property of TSR, which
appears one-source multi-effect. TSR regulates gene expression at the RNA level,
exhibiting high specificity and efficacy without exogenous protein or intracellular
mechanisms. It also has the potential to correct multiple mutations with a
single enzyme, meeting medical unmet needs related to rare and incurable
diseases.”
Rznomics is
building a pipeline RZ-004 for inherited retinitis pigmentosa (RP) treatment
which is one of rare genetic disorders. RP is a progressive inherited degenerative
disease leading to vision loss due to photoreceptor damage and it occurs in 1
in 3,500~4,000 people globally.
30% of autosomal
dominant RP cases are caused by mutations in rhodopsin gene. Rhodopsin,
pigment-containing sensory protein converts light into an electrical signal.
More than 150 rhodopsin mutations have been identified so far, and each mutation
can trigger serious eye disease including retinitis pigmentosa. Current
therapeutic pipelines typically target individual rhodopsin mutations, limiting
their applicability to less than 10% of Western patients; the clinical trial is
suspended at the moment.
It is notable
that RZ-004 can target all rhodopsin mutations by replacing mutant RNA with
normal RNA. Its proprietary engineering skills control the gene expression
level according to the mutation level. There are no competitors in the market,
so once the company passed Phase 2 clinical trial, then it can apply to Accelerated
Approval Program. Rznomics has already received IND approval for RZ-004 in
Australia and patient recruitment will begin within 2025.
A New
Circular RNA Platform
To overcome
limitations of current RNA platforms, Rznomics developed a novel circular RNA
platform. Most RNA-based vaccines and therapeutics are based on linear RNA,
which is vulnerable to Ribonuclease due to its open structure.
Circular RNA, single-stranded
RNA that forms a covalently closed loop, expresses high stability and resistance
against Ribonuclease. Though it is still in early stages globally, this
technology is spotlighted as a new platform to develop vaccines and
therapeutics.
Ribozyme-based
circular RNA synthesis is more prevalent than purely chemical or enzymatic
methods due to its efficiency and scalability. Ribozyme-based technologies rely
on the Permuted Intron-Exon (PIE) approach, which has a limitation that PIE leaves
unintended sequences in the final output. On the other hand, Rznomic’s circular
RNA, based on the Tetrahymena group I ribozyme shows higher efficiency compared
to existing methods.
“Our circular
RNA platform overcame limitations of the previous technologies. What is more
important, it produces the equivalent or higher gene expression compared to PIE,”
Dr. Lee mentioned.
Top Priority:
Recruiting Industry Experts
When Dr. Lee
started the business, his top priority was recruiting experts. “Fortunately, I’m
working with top experts in each field. Thanks to them, I could handle pre-clinical
and clinical development, financial operation which I’m not good at.”
Seongwoo Hong, vice
president of Rznomics, has over 20 years of business development experience in domestic
and global pharmaceutical companies, successfully leading multiple IND filings
and approvals. He is managing the entire development process, including RA, CMC.
Seung-Ryul Han, Head of R&D Center, has researched TSR for a long time
through his BSc, MSc, and PhD at Dankook University. As leading numerous
R&D projects, he acquired a reputation as a specialist in TSR field.
CFO Jong-sun Rim
has over 13 years of experience at PwC Korea, supporting IPO preparations,
internal control advisory, and financial consulting for both public and private
companies.
Making TSR
technology a global standard,
that is Dr. Lee’s vision. He emphasized, “TSR will become an essential tool for
DNA and RNA editing industries. In special indications, it will be the standard
treatment in the near future.”
He is looking
forward to commercializing therapeutics Rznomics researched and developed. “Within
10 years, we will build an in-house manufacturing system from initial research
to GMP production. It will be the stepping stone that Rznomics grow as a global
biopharmaceutical company.”
RNA Editing
Technology Emerges as a Novel Tool for Cancer Gene Therapy
Published in Molecular Therapy – Nucleic Acids (Journal
of the American Society of Gene and Cell Therapy)
Title of the
Study: Targeted Suicide
Gene Therapy for Liver Cancer Based on Ribozyme-Mediated RNA Replacement
Through Post-Transcriptional Regulation
This study aimed
to develop a novel gene therapy for hepatocellular carcinoma (HCC) using a
ribozyme-mediated RNA replacement strategy, leveraging adenovirus-delivered
Tetrahymena group I trans-splicing ribozymes. The therapeutic approach induces
selective apoptosis in cancer cells by targeting human telomerase reverse
transcriptase (hTERT) RNA, which is abundantly expressed in tumor cells, and
replacing it with a suicide gene transcript. Post-transcriptional regulatory
elements were introduced to enhance therapeutic specificity and minimize
toxicity to normal hepatocytes.
To confer
tumor-specific cytotoxicity, the authors engineered the ribozyme to catalyze
trans-splicing of hTERT RNA, replacing it with a transcript encoding Herpes
Simplex Virus thymidine kinase (HSV-tk). Expression and stability of the
therapeutic RNA were improved by incorporating splicing donor and acceptor
(SD/SA) sequences and the Woodchuck Hepatitis Virus Post-transcriptional
Regulatory Element (WPRE). Additionally, to restrict ribozyme activity to
malignant hepatocytes, a target site complementary to miR-122a—a liver-specific
microRNA—was added (miR-122aT), thereby suppressing expression in normal liver
cells.
The optimized
ribozyme showed potent and selective cytotoxicity toward HCC cells in vivo.
In intrahepatic multifocal HCC mouse xenograft
models, the therapy significantly inhibited tumor growth. Preclinical
toxicology and biodistribution studies demonstrated minimal hepatotoxicity, underscoring
the safety and translational potential of this platform.
These findings
highlight ribozyme-mediated trans-splicing RNA replacement as a promising
next-generation strategy for gene therapy in HCC, offering selective tumor
targeting while sparing healthy liver tissue—an essential advancement over
conventional approaches.
This study was
featured as a highlighted article in Molecular Therapy – Nucleic Acids,
a leading journal published by the American Society of Gene and Cell Therapy
(ASGCT).
Rznomics’ TSR
(Trans-Splicing Ribozyme) platform has garnered international recognition. It
was identified as the first RNA editing technology to enter clinical
development in the 2023 Nature Biotechnology RNA editing spotlight
issue, and was cited by Nature in 2024 as one of only three RNA editing
platforms to have progressed to clinical trials.2025-04-11 -
Rznomics: "The World's First RNA Editing Technology for Developing Treatments for Incurable Cancers"
Safer Than Direct Gene Therapy,
Enhanced Specificity for Anticancer Drug Development
Aiming for IPO Through Licensing-Out
Within the Year, "Platform Deals Also Possible"
"We aim to develop the world's first treatment
for incurable cancers using RNA editing technology."
In an interview on March 7, Seongwook Lee,
CEO of Rznomics, stated, "Our proprietary RNA editing platform, Trans-Splicing
Ribozyme (TSR), simultaneously expresses therapeutic RNA while
suppressing unintended RNA expression."
Rznomics was founded in 2017 after CEO Lee
dedicated over 20 years to TSR research. He began studying TSR in the 1990s as
a postdoctoral researcher at Duke Medical Center in the U.S., where the first
research papers on TSR were published.
However, the emergence of RNA interference
(RNAi) in the 2000s led to a decline in TSR development momentum. As global
interest in RNAi-based therapeutics surged, many scientists who had been
working on TSR shifted their focus to RNAi research. Lee returned to Korea and
continued his TSR research as a professor at Dankook University.
"When TSR was developed at first, it
lacked specificity and efficacy, and there was little research on delivery
vectors for in vivo applications," he explained. "However, in the
mid-2000s, through advancements in bioengineering, we achieved the ability to
target specific genes for cancer treatment. The emergence of gene therapies
utilizing viral vectors as drug delivery systems further accelerated TSR
development."
A Safer Alternative to Gene Editing
Gene-editing therapies such as CRISPR gene
scissors pose concerns about irreversible genetic modifications if unintended
targets are altered. Furthermore, there are currently no treatments that enable
gene editing inside the human body post-administration. RNAi therapies also
face limitations, as existing drug delivery systems are primarily designed for
targeting liver cells, requiring further research for development as anticancer
drugs.
On the other hand, TSR does not directly
modify DNA. Instead, it removes targeted RNA and replaces it with therapeutic
RNA. Rznomics designs optimized drug delivery systems for each disease,
allowing precise targeting of the intended site. Depending on the indication, adenoviral
vectors are used for temporary effects, while adeno-associated virus (AAV)
vectors are used for long-lasting, one-time treatments.
Lead Pipeline: RZ-001
Rznomics’ lead pipeline candidate is
RZ-001, an anticancer drug currently in clinical trials. In both the U.S. and
Korea, RZ-001 is undergoing Phase 1b/2a trials for hepatocellular carcinoma
(HCC) and Phase 1/2a trials for glioblastoma (GBM). The U.S. Food and Drug
Administration (FDA) has granted Fast Track designation for both indications.
Additionally, the glioblastoma program has been designated under the Expanded
Access Program (EAP), which allows patients with no available treatment options
to receive the investigational drug.
RZ-001 is also set to enter combination
trials with immune checkpoint inhibitors. Rznomics has secured free-of-charge
supply agreements for Roche’s Tecentriq and Celltrion’s Vegzelma (Avastin
biosimilar) for domestic combination studies with RZ-001. Tecentriq and Avastin
have already been approved by the FDA as a first-line treatment for
hepatocellular carcinoma.
"In preclinical studies, RZ-001 showed
improvements in biomarkers associated with immune checkpoint inhibitor
responses," Lee said. "Due to the anticipated synergy with Tecentriq
and Avastin, we were able to secure these drugs free of charge for our
trials."
IPO Target and Global Licensing Plans
Rznomics aims to list on the KOSDAQ stock
market through a special listing track as early as this year or by next year at
the latest. "Our TSR technology offers not only pipeline assets but also platform
licensing opportunities," Lee emphasized. "We plan to achieve licensing-out
deals within the year and apply for a technology evaluation to proceed with our
IPO."2025-03-12 -
Rznomics’ Liver Cancer Treatment Receives FDA Fast Track Designation
Gene Therapy-Based Cancer Drug Candidate RZ-001 Gains Fast Track Status for Hepatocellular Carcinoma, Following GlioblastomaRznomics announced on the 17th that its gene therapy-based cancer drug candidate, RZ-001, has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of hepatocellular carcinoma.This is the second Fast Track designation for RZ-001, following its 2023 designation for glioblastoma, an aggressive and hard-to-treat brain cancer.Fast Track is an FDA program designed to expedite the development and review of drugs intended for serious or life-threatening conditions. It allows companies to have more frequent communication with the FDA, benefit from priority review, and submit their application for rolling review—where different sections of the application are reviewed as they become available, rather than waiting for the full submission—potentially speeding up the approval process.RZ-001 is being developed using Rznomics' proprietary RNA editing and correction platform, which is based on ribonucleic acid substitution enzymes. The company is currently conducting Phase 1b/2a clinical trials for hepatocellular carcinoma and Phase 1/2a trials for glioblastoma in South Korea, with FDA approval to conduct the same trials in the United States.For glioblastoma, Rznomics has also received FDA approval for an Expanded Access Program (EAP), allowing compassionate use of RZ-001. This program is currently being conducted at Harvard University Hospital.Seong-wook Lee, CEO of Rznomics, stated, "This Fast Track designation reaffirms the potential of RZ-001 as an innovative cancer treatment. We are committed to accelerating clinical development to provide effective treatment options for patients suffering from difficult-to-treat cancers."
2025-02-17 -
"Ultimately, Deep Science and Rational Evidence Win Over Investors"
Rznomics' Strategy for Investor Confidence Ahead of Special Technology-Based IPO"Rational evidence and global competitiveness are essential.""Without deep science, supported by rational evidence and global competitiveness, it is challenging to win the hearts of investors."Rznomics CEO Seongwook Lee is pioneering the field of RNA-based therapeutics through scientific rigor. In a recent interview with Hit News, he elaborated on the strengths of the company’s Trans-splicing Ribozyme technology, its circular RNA platform, and a vision for expanding therapeutic indications based on global competitiveness. Last month, Rznomics successfully secured KRW 20.3 billion in Pre-IPO funding.Revolutionary RNA Editing and Correction TechnologyRznomics is gaining attention in the field of RNA-based therapeutics for its innovative technology. The company’s core Trans-splicing Ribozyme platform replaces mutated RNA with normal RNA, enabling the production of functional proteins. Unlike conventional DNA-based gene therapies, which alter entire genomes, this technology selectively edits or replaces only the specific RNA implicated in disease."Our technology is reversible, making it safer and more controllable compared to DNA therapies, which carry the risk of permanently altering cellular genes," said CEO Lee.By focusing on targeted RNA segments instead of delivering entire RNA genomes, Rznomics optimizes the use of Adeno-associated virus (AAV) vectors. "Although AAV vectors have size limitations for delivered genomes, our technology’s selective RNA replacement approach minimizes these constraints," Lee explained. He added that AAV vectors demonstrate stable activity in non-dividing cells and enable prolonged RNA expression, particularly benefiting diseases such as central nervous system (CNS) and retinal disorders, where long-term treatments are crucial.Describing the therapeutic mechanism, Lee likened it to installing a factory within non-dividing cells: "By administering AAV, we can continuously produce therapeutic RNA (Trans-splicing Ribozyme). A single administration could provide sustained therapeutic effects."For diseases like cancer, where genetic material doesn’t need to remain long-term, Lee emphasized the advantages of RNA-based therapies, which achieve therapeutic effects while minimizing side effects. For such indications, Rznomics uses adenovirus vectors, which work temporarily without integrating into the chromosome—making them ideal for cancer treatment.Another strength of Rznomics' technology is its ability to address diverse mutations with a single drug. "Even if patients have mutations in different regions, we can map specific RNA sequences and develop a single therapy to correct multiple mutations," Lee said.The platform also avoids risks associated with overexpression by controlling RNA expression levels. Traditional RNA therapies often trigger off-target effects or overexpression, leading to undesirable side effects. In contrast, "Our technology ensures target specificity by replacing only the intended RNA. This allows the production of proteins at normal levels, effectively eliminating the risk of overexpression," Lee explained.Highlighting the platform’s versatility, Lee stated, "Rznomics' technology is modular. If a target RNA is identified, a corresponding therapeutic RNA can be developed, paving the way for new treatments in incurable and rare diseases with unmet medical needs."A New Frontier: Circular RNA TherapeuticsIn addition to Trans-splicing Ribozyme technology, Rznomics is developing a cutting-edge circular RNA platform. Unlike linear RNA, circular RNA forms a closed-loop structure with no open ends, making it resistant to degradation and enabling long-lasting functionality within cells."When linear RNA is used as a therapeutic, modified nucleotides are often needed to suppress immune responses. However, circular RNA works safely in cells without modifications," Lee explained.Rznomics’ proprietary circular RNA technology eliminates unnecessary sequences and is composed entirely of the desired gene of interest (GOI), enhancing cellular safety. Lee noted that circular RNA has potential applications in advanced cell and gene therapies, including in vivo CAR-T therapies, simplifying the manufacturing process by bypassing complex cell manipulation steps.However, Lee acknowledged that circular RNA remains in its early stages and requires further research and development to prove its commercial viability. "Leading groups in the U.S. are exploring applications of circular RNA in areas like vaccines and in vivo CAR-T therapies. However, identifying the most competitive use case for this technology and addressing challenges in large-scale production remain key tasks," he said.Rznomics Gains Global RecognitionRznomics' innovations in RNA-based therapies have earned recognition from the global scientific and pharmaceutical communities. The company’s groundbreaking research has been featured in leading journals such as Nature Biotechnology and Nature, underscoring its scientific credibility."The trust we’ve gained from the global academic and industrial communities is a significant asset," Lee said, emphasizing the role of scientific validation in attracting investments and driving the company’s growth.Rznomics has also secured Orphan Drug Designation (ODD) and Fast Track Designation from the U.S. Food and Drug Administration (FDA), further solidifying its commercial potential. "Recognition from the FDA sends a strong signal to global pharmaceutical companies and supports our independent market entry efforts," Lee noted.Building on these achievements, Rznomics is actively collaborating with global pharmaceutical companies to accelerate commercialization. "We are establishing partnerships with several companies to expedite market entry while simultaneously validating and commercializing our technologies," Lee said.Rznomics remains committed to applying its innovations to improve patient outcomes. "Our goal is to provide better treatment options for patients by expanding the potential of our platform," Lee concluded, reaffirming the company’s vision to lead the global RNA therapeutics market with its differentiated competitive edge.
2025-01-23 -
Rznomics Secures KRW 20.3 Billion in Pre-IPO Funding, Bringing Total Investment to KRW 81.2 Billion
RNA-based gene therapy developer Rznomics announced on the 23rd that it has successfully raised KRW 20.3 billion in a Pre-IPO funding round.The round was led by KB Investment as the anchor investor, with additional participation from Yuanta Investment, the manager of the first K-Bio Vaccine Fund designated by the Ministry of Health and Welfare, and Samsung Venture Investment as new investors. Existing investors, Aon Investment and Quad Ventures, also participated through follow-on investments.With the addition of this Pre-IPO round, Rznomics has now raised a total of KRW 60.9 billion, including KRW 81.2 billion secured through its Series C funding round in June 2022. Additionally, the company has received approximately KRW 9 billion in government research funding through various national projects.Rznomics' proprietary platform is an RNA editing and correction technology based on RNA replacement enzymes. This groundbreaking approach rewrites entire RNA sequences, replacing the target RNA region with therapeutic RNA. Unlike conventional DNA or RNA editing technologies, Rznomics' platform does not require external proteins or cellular tools. Moreover, while base-editing technology focuses on correcting single-point errors, Rznomics’ platform can address a broad range of mutations with a single therapeutic agent.The newly secured funding will enable Rznomics to accelerate its R&D efforts and further strengthen its financial foundation. The company plans to apply for a technology assessment for a special technology-based IPO listing in the first half of next year and submit a preliminary IPO application in the second half.Notably, Rznomics is the first company to be selected as a National Strategic Technology firm by the Ministry of Science and ICT. It is also the only company to hold both the "Research/Development" and "Possession/Management" tracks for National Strategic Technology, positioning itself to leverage a special listing process for cutting-edge technologies.Rznomics CEO Seongwook Lee said, “It is incredibly encouraging to see Rznomics' potential and value recognized despite the current challenges in the biotech market. This provides us with the motivation to accelerate our research and clinical development efforts.”He added, “We are actively engaging with leading global pharmaceutical companies, and we have already completed technology validation through an MTA with one of them. We are now negotiating technology transfer agreements to develop treatments for unmet medical needs using the Rznomics platform.”
2025-01-20 -
Candidate for Rznomics Glioblastoma Treatment, Approved FDA Expanded Access Program
Candidate for Rznomics Glioblastoma
Treatment, Approved FDA Expanded Access Program
Available to critically ill patients prior to authorization
Expect to gain more patient data
A gene therapy drug-based anticancer drug being developed by Rznomics can be
used for humanitarian purposes to critically ill patients prior to approval.
Rznomics announced on the 14th that its candidate "RZ-001" has been
approved for sympathetic use (EAP) by the U.S. Food and Drug Administration
(FDA).
EAP refers to a system that provides humanitarian assistance to patients in
critical condition for new drugs that are in the clinical trial stage prior to
approval. RZ-001 can be used in patients with glioblastoma in critical
condition thanks to this approval.
Rznomics is conducting phase 1/2a clinical trial on patients with glioblastoma
after obtaining approval for clinical plan (IND) from the Food and Drug
Administration and the FDA. "We expect that we will be able to secure more
patient data through this EAP," a company source said. RZ-001 was also
designated as a fast track by the FDA in November last year.
Glioblastoma is a carcinoma that occurs in the brain and has a survival period
of less than a year in case of recurrence, which is a disease that has very
high medical demand. On the other hand, it is considered a representative
refractory tumor with insufficient treatment methods.
"We plan to expand the target hospitals starting with Harvard University
Hospital, reflecting the high interest of U.S. researchers in RZ-001's
EAP," said Sung-woo Hong, vice president of Rznomics. "This program
is expected to have positive results in terms of effectiveness as it can apply
high-concentration test drugs immediately."
Seong-wook Lee, CEO of Rznomics, said, "We hope that it will be a good
treatment alternative for patients who are difficult to treat with existing
drugs. We will do our best to get permission quickly through efficient clinical
development."2024-10-15 -
Rznomics Wins the Korea Innovation Startup Award led by K-Deep Tech
Rznomics (CEO Seong-wook Lee, Graduate Bio-convergence Engineering Department) a subsidiary of the Industry-Academic Cooperation Group received the Chairman's Award of Central Holdings at the "2024 Korea Innovation Startup Award" selected by the Korea Advanced Institute of Science and Technology (KAIST) as an outstanding R&D-based K-Deep Tech company.Deep-locked technology that has not yet been discovered is called deep-tech. The "Korea Innovation Startup Award" is supporting deep-tech startups armed with innovative technologies and creative IDs to establish themselves as growth engines for the Korean economy.KAIST, Seoul National University, and Central Holdings cooperated and sponsored by the Ministry of Science and ICT. The award ceremony was held at the "Korea International Symposium 2024 for Innovative Start-up Countries" held at Seoul National University on the 11th (Wednesday).Based on RNA editing technology, Rznomics Inc., founded in 2017, is innovating biotechnology and opening a new horizon in the development of new drugs by developing gene therapy drugs for rare and intractable diseases. KAIST and Seoul National University praised Rznomics Inc.'s technological prowess and recent achievements.The key to Rznomics Inc.'s technology is to remove RNA that causes cancer or genetic diseases and at the same time substitute 1:1 therapeutic RNA at the cut RNA site. △ Domestic and foreign patent registration △ Clinical approval of anticancer gene therapy products by the Korea Food and Drug Administration (FDA) △ Clinical approval by the Australian Federal Drug Administration (TGA) for genetic disease gene therapy products.Recently, the U.S. Food and Drug Administration (FDA) designated rare drugs for liver cancer of the anticancer drug "RZ-001" and designated a fast track for brain cancer, and was selected as the first in the research and development field of the government-recognized national strategic technology confirmation system.Professor Seong-wook Lee said, "I am happy to be recognized for the progressiveness and innovation of the company's technology through the award of the Korea Innovation Startup Award," adding, "We will do our best to contribute to the development of advanced technologies in the bio sector and the future growth of the country."Professor Seong-wook Lee's research team, who has been silently researching RNA editing technology at our university for the past 20 years, is happy to be recognized for its technological prowess as another innovative start-up award, President Ahn Soon-cheol said. "Our university will lead the industry-academic cooperation ecosystem to an entrepreneurial university by discovering and supporting teachers who will write the myth of the 'Second Rznomics-Professor Seong-wook Lee'."
2024-09-26 -
Gene Therapy Is Developing Rapidly in the Asia Pacific
The Asia-Pacific gene therapy market was valued at $349.1 million in 2020 and is expected to grow at a compound annual growth rate (CAGR) of 36.8% to reach nearly $7 billion in 2030. This predicted exponential growth is attributed to factors that include the surging burden of chronic diseases, the growing number of positive clinical trials, and the increase in gene therapy-based biotech companies. We discuss here the journeys of three gene therapy startups in South Korea, Japan and China, and how their products will or are already making a difference for patients.Rznomics was founded in 2017 by Seong-Wook Lee, PhD, of the department of bioconvergence engineering at Dankook University, Yongin, South Korea. The core technology of the company is “trans-splicing ribozyme-based RNA editing,” in which the trans-splicing ribozyme specifically targets and cleaves disease-causing or related RNA, and trans-ligates with the therapeutic RNA to induce therapeutic effect. This brings about a down-regulation of the target RNA, and the therapeutic RNA is expressed selectively in cells that express the target.“There are numerous advantages of our platform,” says Lee, CEO of Rznomics. “No cellular machinery in the cell is needed and no external protein needs to be provided as the ribozyme performs trans-splicing and ligation by itself. The target RNA can be any RNA species including mRNA and non-coding RNA, which expands the range of therapeutic targets. Additionally, all mutated RNAs can be edited with one molecule through targeting the upstream region of known mutation sites.”Currently, Rznomics has five pipeline drugs based on its trans-splicing ribozyme technology to address different human diseases such as cancer, neurodegeneration, and genetic eye disorders. One of its products, RZ-001, is already in phase I/IIa trials for treatment of hepatocellular carcinoma and glioblastoma.“RZ-001 is replication-incompetent adenoviral vector encoding a human telomerase reverse transcriptase (hTERT) targeting trans-splicing ribozyme,” says Lee. “The trans-splicing ribozyme recognizes and cleaves the hTERT mRNA, and it replaces the hTERT mRNA with Herpes Simplex Virus thymidine kinase, which is used as a suicide gene. With the co-administration of prodrug ganciclovir (GCV), the phosphorylated GCV blocks DNA replication in targeted cancer cells, thereby leading to apoptosis and anti-cancer effect.”The company has received Orphan Drug Designation for RZ-001 targeting hepatocellular carcinoma and Fast Track Designation for RZ-001 treating glioblastoma from the US FDA. The phase 1 clinical trial for RZ-001 treating glioblastoma already began in Korea and patient screening process is underway. The company also plans to commence clinical trial for RZ-001 in combination with atezolizumab and bevacizumab in subjects with hepatocellular carcinoma later this year.For this clinical trial, Rznomics has signed a Clinical Trial Collaboration and Supply Agreement with Roche and Celltrion, who will provide atezolizumab and bevacizumab, respectively. “We are expanding indications beyond cancer to incurable and rare diseases with highly unmet medical needs that are difficult to be addressed with the existing therapies,” says Lee. “As part of this effort, CTN was recently secured from the Australian TGA for a clinical trial treating autosomal dominant retinitis pigmentosa.”Gene therapy cures deaf children in ChinaCongenital deafness affects approximately twenty-six million individuals worldwide and has no current pharmacological treatments. Traditional interventions for hearing loss, such as cochlear implants and hearing aids, have been the mainstay of clinical management. While these devices can provide substantial benefit, they do not restore natural hearing. Cochlear implants, though effective for severe hearing loss, also have shortcomings, such as sound discrimination in noisy environments and music appreciation due to transmitting sound through electrical signals.“Gene therapy, by contrast, targets the genetic roots of hearing loss, aiming to restore natural hearing,” says Yilai Shu, MD, PhD, professor at the Eye and Ear, Nose and Throat (ENT) Hospital of Fudan University. “Focusing on the OTOF gene, one of the prevalent genes associated with hereditary deafness, we have confirmed a dual AAV-mediated gene therapy. This innovative therapy led us to conduct the world’s first-in-human clinical trial to investigate the safety and efficacy of gene therapy for congenital deafness.”Preliminary results from their recent study, which was published in The Lancet, demonstrated remarkable outcomes for patients who received unilateral gene therapy and exhibited an improvement of hearing and enhancement of capability of speech perception. Those receiving gene therapy bilaterally not only regained hearing in both ears but also showed improvements in distinguishing sounds in noisy environments, the ability to locate sound sources, and the capability to appreciate music.“Gene therapy is a promising advancement in the treatment of deafness and offers hope to other patients who suffer from congenital deafness around the world,” says Shu. “Our team at Fudan University is collaborating with Refreshgene Therapeutics, a company in Shanghai, China that specializes in the development of gene therapy drugs for rare diseases, genetic disorders, and other chronic conditions, to develop a gene therapy drug targeting the OTOF gene.”Shu adds that given that the multitude of over two-hundred identified genes that contribute to deafness, his team is dedicated to advancing treatments for various forms of hearing loss. “Beyond OTOF, we are exploring new strategies such as gene editing and gene replacement for other genes like GJB2, KCNQ4, and TMC1. Additionally, we’re delving into treatments for acquired hearing loss to benefit a wider patient population suffering from hearing loss.”In addition to treating deafness, a gene therapy product developed in partnership with Refreshgene Therapeutics named RRG001, is designed for patients with neovascular age-related macular degeneration. This drug is currently undergoing Phase I/IIa clinical trials in China, marking a significant step forward in the treatment of the eye disease in the country.Japan’s first gene therapyCollategen® is the first gene therapy product approved in Japan as well as the first such therapy in Asia as well as the world targeted at critical limb ischemia. Collategen is a naked plasmid DNA that is delivered intramuscularly before being transcribed and translated in cells into hepatocyte growth factor. The product has been shown to promote blood vessel formation (angiogenesis) and is indicated for patients with arteriosclerosis obliterans and Buerger’s disease accompanying critical limb ischemia that is not amenable to surgical revascularization, leaving no other effective treatments available. There are about 500,000 such patients in the U.S., 20–40% of whom find conventional treatments ineffective.Collategen was initially developed in the lab of Ryuichi Morishita, MD, PhD, professor of clinical gene therapy at Osaka University and further developed at AnGes, a company founded by Morishita and where he now serves as a medical advisor. “It took us many years before getting Collategen approved,” he says. “As we were the first company to do so, we had to educate regulators what gene therapy is, and to show that it is efficacious and safe. This indication is also challenging as regulators are more familiar with life-threatening diseases like cancer, and critical limb ischemia is not considered life threatening.”Morishita sees a bright future for gene therapy in Asia and the world and expects to see more products in the next 10 years. However there are still a few challenges to address to make gene therapy more widely available.“Genetic material like DNA needs to be delivered to the target tissue site and cell. Therefore, development of viral vectors and non-viral material like lipid nanoparticles is crucial to improve the half-life of the DNA plasmids,” says Morishita. “I would also encourage researchers to think outside of the box. For instance, there is active research in using adipose-derived stem cells which can be genetically engineered to express target proteins. One can think of using these engineered cells as factories that home to target body sites and produce therapeutic proteins.”Another challenge, Morishita adds, is translation from preclinical models to human subjects. “There is obviously a translational gap,” he says. “In order for us to accurately determine gene therapy dose, we need more data, but clinical trials for gene therapy are rare and expensive. Essentially, it is a chicken and egg problem here. We need ways to make clinical trials more affordable and faster so we can move the products quicker into the clinics to benefit patients.”The future of gene therapy in Asia Morishita shared his experience launching Collategen and how payment models in countries affect the progress of gene therapy. “In Japan, the government sets the price of new products such as for gene therapy, but in the United States the private companies set the price. When governments set the price, they calculate it based on quality-adjusted life years which can be hard to determine and often restrictive. This can disincentivize homegrown companies in Japan and Asia from launching products in their home countries in favor of the United States market. Researchers therefore need to work closely with regulators on product pricing so that residents in their home countries can also benefit from biomedical innovations.”Shu shares Morishita’s sentiments and adds that investment in healthcare infrastructure is needed to ensure that hospitals and clinics have the facilities and expertise to administer gene therapy safely and effectively. There is also a need to increase public understanding of genetic diseases and the potential of gene therapy, which can help build trust and support for these treatments. Educational activities should target both the general public and healthcare professionals. Gene therapies can be prohibitively expensive, so innovative pricing models, insurance coverage, and government subsidies may be required to make these treatments affordable to a broader population.“By addressing these challenges, the Asia-Pacific region can pave the way for patients having greater accessibility and affordability to gene therapy,” says Shu. “It will not only benefit patients by providing them with potentially life-changing treatments but also contribute to the global advancement of medical science. Collaboration among governments, industry, academic institutions, hospitals, and patient advocacy groups will be crucial in realizing this vision.”
2024-09-26 -
Rznomics gets approves U.S. FDA For anticancer Candidate Based On Gene Therapy
Rznomics gets approves U.S. FDA For anticancer Candidate Based On Gene Therapy
RZ001+T-Sentric + Avastin
Approved Phase 1b/2a clinical trial for hepatocellular carcinoma patients
Rznomics, a gene therapy drug-based anticancer drug developer, will start
clinical trials in the United States that use its candidate and immune
anticancer drugs in combination.
Rznomics announced on the 19th that it has received approval from the U.S. Food
and Drug Administration (FDA) for its phase 1b/2a clinical trial in which the
anticancer drug candidate "RZ-001" and immuno-cancer drugs are
combined.
The plan is to evaluate both effectiveness and safety by co-administering
RZ-001 together with the first standard treatment (Tscentrick + Avastin) to
about 50 patients diagnosed with hepatocellular carcinoma.
RZ-001 is an anticancer drug candidate that is being developed by applying the
RNA editing platform technologies owned by Rznomics. It targets telomerase
(hTERT) RNA, which is specifically expressed in cancer cells, by delivering RNA
enzymes with adenovirus as a vector.
Normal cells become shorter in telomeres, and when there is not much time left,
they perceive themselves to be 'old' and die without further dividing. However,
in cancer cells, telomerase, an enzyme that increases the length of telomeres
that is decreasing again, is overactive, and telomeres may continue to
lengthen. This is the cause of cancer cells continuing to divide without dying.
RZ-001 removes hTERT RNA from hepatocytes that have become cancerous cells so
that telomerase is not expressed. It induces apoptosis by making telomeres
shorten normally. HSV-TK is also expressed at the cut hTERT site. Antiviral
drugs (balgancyclover) administered with RZ-001 selectively attack only
cancerous cells in response to this gene.
It is a dual mechanism that removes the telomerase gene that causes infinite
proliferation of cancer cells and inserts virus-derived genes to cause antiviral
drugs to attack cancer cells.
The FDA-approved clinical trial was combined with ticentric + avastin, which is
the most widely used first-line treatment for hepatocellular carcinoma. If
differentiated safety and efficacy are demonstrated compared to existing
treatments, it could open the way for them to enter the largest market of
first-line treatments.
Rznomics plans to collaborate with large domestic and international
pharmaceutical companies for this clinical trial. Among the clinical drugs,
atetzolizumab has been contracted to receive supply from Roche and bevacizumab
from Celltrion.
Seong-wook Lee, CEO of Rznomics, said, "As many researchers and
institutions cooperate in RZ-001 clinical development, we will do our best to
succeed as an innovative anticancer drug."2024-08-28
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