RIBOZYME AND OMICS
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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."
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'."
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.”
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."
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 pharmtecoSK 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 RznomicsRznomics 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.
Rznomics gets approval from Clinical Trial Plan for Genetic Retinopathy
Rznomics announced on the 8th that it has received a
notification from the Australian Federal Drug Administration (TGA) on the
completion of the approval process for its phase 1 clinical trial plan for
RZ-004, which is being developed as a treatment for hereditary retinal pigment
degeneration.
In order to conduct clinical trials of gene therapy drugs in
Australia, it is necessary to undergo preliminary deliberation from the Office
of the Gene Technology Regulator (OGTR) as a preliminary stage for approval of
clinical plans.
Rznomics completed the procedure in January of this year.
This means that all deliberation and administrative procedures for clinical
initiation in Australia have been completed.
Retinitis Pigmentosa is a disease in which visual cells are damaged and the visual field
becomes narrower, resulting in loss of vision. As pigment builds up in the
retina, retinal function disappears, which is well known as a rare and
incurable disease. It occurs in one out of every 3,500 to 4,000 people
worldwide.
RZ-004 removes the mutated Rhodopsin ribonucleic acid (RNA)
and replaces it with a normal rhodopsin gene using the RNA trans-splicing
ribozyme Editing Technology owned by RZ-004 to induce vision damage suppression and
vision recovery. In particular, RZ-004 has a groundbreaking feature that can
correct more than 150 different rhodopsin mutations known so far with a single
treatment.
Australia has excellent medical system and medical staff
capabilities, the number of target patients, patient compliance, and support
from regulatory agencies, said Sung-woo Hong, head of the development division
of Rznomics. "We will expand our clinical development countries to the
United States and Europe, starting with Australia."
The approval of the clinical plan means that it has entered
the clinical stage for genetic diseases that can make good use of the
characteristics of the company's platform technology following the clinical
entry of several anticancer drug pipelines, said Seong-wook Lee, CEO of Rznomics.
"Since the target disease of RZ-004 is a disease with very high unmet
medical demand without any approved treatment, we will do our best to provide
treatment opportunities to suffering patients and improve their quality of
life."
The RNA-based new drug development company Rznomics has
been selected as the first case in the national strategic technology
verification system, with their technology ' RNA
Trans-splicing Ribozyme-based gene therapy and Circular RNA Platform.'
The Ministry of Science and ICT and the Korea Institute
of S&T Evaluation and Planning (KISTEP) announced on the 28th that they
have notified the results of the "1st National Strategic Technology
Verification Application."
This system, introduced on March 15th, verifies whether
technologies held or under R&D by research institutions, universities, or
companies fall under national strategic technologies.
A total of 130 applications were received this time, and
the review results notified that one was eligible and five were deferred.
Rznomics' technology was confirmed to fall under the
category of gene delivery technology R&D among national strategic
technologies. This technology can remove target RNA that causes intractable
diseases and express therapeutic RNA, making it a gene therapy technology.
The five technologies deferred for further review were
notified as such due to insufficient evidence and will be re-evaluated upon
resubmission of supplementary data during the next announcement of the
verification system.
Kwon Seok-min, Director General of the Science and
Technology Policy Bureau at the Ministry of Science and ICT, said, "As the
national strategic technology nurturing and support system is still being
established, with public-private efforts to secure national strategic
technologies ongoing, we expect that the number of national strategic
technology verifications will increase in the future."
Applications for national strategic technology
verification are possible quarterly, with the second round of applications to
be conducted in July.
If a company confirmed to possess national strategic
technology has a market capitalization of at least 100 billion KRW and has
raised over 10 billion KRW in venture financing in the last five years, they
can apply for a technology exception listing with just one technology
evaluation rated A or higher.
Previously, it required two technology evaluations, each
rated at least A and BBB, respectively.
Development of RNA
trans-splicing ribozyme Editing Technology
"Will grow into an Innovative Therapeutics
Development Company"
Rznomics, a new drug development company based
on RNA trans-splicing ribozyme editing
technology, announced on the 24th that it has been selected as a new company
for the 'Deep tech Incubator Project for Startup (DIPS) 1000+'.
The 'Deep tech Incubator Project for Startup
1000+' project is led by the Korea Institute of Startup & Entrepreneurship
Development under the Ministry of SMEs and Startups. From last year until 2027,
the project aims to select and support startups with unique technological
superiority in ten key future-leading fields such a bio, healthcare, system
semiconductors, and next-generation nuclear power, to foster them into global
unicorns.
Through this
project selection, Rznomics will receive direct business funding of up to 600
million KRW over the next three years, along with linked support for policy
funds, guarantees, exports, and specialized support tailored to industry
characteristics.
Seong-wook Lee,
CEO of Rznomics, said, "We are delighted that the selection for the DIPS
1000+ project has once again recognized the innovation and growth potential of
Rznomics’ technology. With the support from this selection, we will focus on
ongoing clinical trials and technology commercialization to grow into a leading
company in developing innovative therapeutics for various rate and intractable
diseases.
Rznomics Signs Clinical Trial Collaboration Agreement With Celltrion for Hepatocellular Carcinoma Combination of RZ-001, Atezlizumab, and Bevaciuzumab to be evaluated for safety and efficacy in Hepatocelluar Carcinoma clinical trial.Rznomics and Celltrion announced on the 14th that they have signed a clinical collaboration agreement to evaluate the combination of RZ-001 and Bevacizumab for hepatocellular carcinoma patients.Through this partnership, Celltrion will provide Rznomics with Bevacizumab (product name Begzelma) and, in return, will receive the right of first negotiation for the Korean regional license after Rznomics’ RZ-001 Phase 1b/2a clinical trial.Rznomics plans to explore the efficacy and safety of adding its RZ-001 to the combination therapy of Atezolizumab and Bevacizumab, the first-time standard treatment for hepatocellular carcinoma, in a Phase 1b/2a clinical trial. Last November, Rznomics entered into a clinical collaboration agreement with Roche, including the free supply of Atezolizumab (product name: Ticentric).By incorporating RZ-001, which employs its proprietary trans-splicing ribozyme-based RNA reprogramming and editing technology, into the combination therapy of atezolizumab and bevacizumab, Rznomics expects to achieve stronger effects and higher response rates.RZ-001, an RNA trans-splicing enzyme-based cancer gene therapy, targets and cleaves telomerase messenger RNA (hTERT mRNA, replacing it with therapeutic gene RNA. It selectively suppresses hTERT expression in cancer cells expressing hTERT and reprograms the hTERT mRNA to encode HSVtk, inducing cytotoxic effects and anticancer activity. Preclinical studies have shown that when used in combination with atezolizumab and bevacizumab, RZ-001 significantly enhances anticancer efficacy in a dose-dependent manner. Sung-woo Hong, vice president and head of development at Rznomics' expressed confidence that RZ-001 could overcome the limitations of the atezolizumab and bevacizumab combination therapy.Seong-wook Lee, CEO of Rznomics, stated, “We are delighted to collaborate with a global biotechnology company like Celltrion,” and added, “We hope this collaboration will help provide new therapeutic options for patients in need.”Sung-hyun Kim, head of medical affairs at Celltion, also emphasized their commitment to continuous efforts in new drug development through partnerships with biotech companies possessing promising technologies and platforms like Rznomics.