Bevacizumab biosimilar (Celltrion)

YUFLYMA ® (adalimumab-aaty) is a high-concentration (100mg/mL) and citrate-free formulation of Humira ® (adalimumab) biosimilar, that is now interchangeable [1] Interchangeable designation of YUFLYMA ® is supported by positive data from the Phase III interchangeability study in patients with moderate-to-severe plaque psoriasis INCHEON, South Korea, April 14, 2025 /PRNewswire/ -- Celltrion, Inc. today announced that the U.S. Food and Drug Administration (FDA) has designated YUFLYMA ® (adalimumab-aaty), as an interchangeable biosimilar to Humira ® (adalimumab). YUFLYMA is an FDA-approved, high-concentration (100mg/mL) and citrate-free formulation of Humira® biosimilar, approved for multiple inflammatory indications.[1] "With this new designation, YUFLYMA is further positioned to help more patients gain access to and afford the therapy they need," said Thomas Nusbickel, Chief Commercial Officer at Celltrion USA. "YUFLYMA has the same dosage form, route of administration, and dosing regimen as the reference product. The pharmacist's ability to substitute the biosimilar directly at the pharmacy without the hassle of a new prescription and without the patient having to learn a new method of administration can be a game changer in increasing patient access to adalimumab." The interchangeable designation was supported by data from the Phase III interchangeability study, which demonstrated similar outcomes in terms of pharmacokinetics, efficacy, safety and immunogenicity in patients with moderately to severely active plaque psoriasis who received reference adalimumab (ADA) continuously and those who alternated between reference ADA and YUFLYMA during the dosing interval of Week 25-27. The result of the interchangeability study was presented at the European Academy of Dermatology & Venereology (EADV) 2024.[2] FDA-approved interchangeable biosimilars may be substituted for the reference product at the pharmacy without the intervention of the prescribing health care provider, subject to state laws.[3] The high-concentration form of YUFLYMA was FDA-approved in May 2023 and is currently available as 20mg, 40 mg and 80mg solution for injection in a prefilled syringe and in an autoinjector pen. YUFLYMA was introduced into the US commercial market on July 2, 2023. YUFLYMA is available in two pricing options to help provide more affordable options for patients. Adalimumab-aaty, the unbranded version, is priced at an 85% discount to the current wholesale acquisition cost (WAC) list price of Humira (adalimumab), providing economic benefits for patients and overall healthcare system. The branded version is priced at a 5% discount to the current WAC of Humira (adalimumab). Notes to Editors: About YUFLYMA® (CT-P17, biosimilar adalimumab-aaty)[1] YUFLYMA is the world's first proposed high-concentration, low-volume and citrate-free adalimumab biosimilar to receive European Commission approval. YUFLYMA is FDA approved for the treatment of patients with rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa and uveitis. YUFLYMA has been designated by the FDA as an interchangeable biosimilar in a prefilled syringe. YUFLYMA is a recombinant fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody. YUFLYMA is available in 20mg/0.2mL, 40mg/0.4mL and 80mg/0.8mL. IMPORTANT SAFETY INFORMATION[1] This important safety information also applies to YUFLYMA® (adalimumab-aaty) SERIOUS INFECTIONS Patients treated with adalimumab-aaty are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue adalimumab-aaty if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before adalimumab-aaty use and during therapy. Initiate treatment for latent TB prior to adalimumab-aaty use. Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with adalimumab-aaty prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with adalimumab-aaty, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy. Treatment with adalimumab-aaty should not be initiated in patients with an active infection, including localized infections. Patients over 65 years of age, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Discontinue adalimumab-aaty if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with adalimumab-aaty, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy. Drug interactions with biologic products: In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of adalimumab-aaty with abatacept or anakinra is not recommended in patients with RA. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of adalimumab-aaty and other biologic products for the treatment of RA, PsA, AS, CD, UC, PS, and HS. Concomitant administration of adalimumab-aaty with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions. A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including adalimumab products. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to the use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. Consider the risks and benefits of TNF blocker treatment including adalimumab-aaty prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC), or when considering continuing a TNF blocker in patients who develop a malignancy. In controlled portions of clinical trials of some adalimumab products, more cases of malignancies have been observed compared to control-treated adult patients. Non-melanoma skin cancer (NMSC) was reported during clinical trials for patients treated with adalimumab products. During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, PS, HS and UV, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, particularly those with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, for the presence of NMSC prior to and during treatment with adalimumab-aaty. In clinical trials of some adalimumab products, there was an approximately threefold higher rate of lymphoma than expected in the general U.S. population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to severalfold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Postmarketing cases of acute and chronic leukemia were reported with the use of a TNF blocker in RA and other indications. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving adalimumab were lymphomas; other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. HYPERSENSITIVITY Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of adalimumab-aaty and institute appropriate therapy. HEPATITIS B VIRUS REACTIVATION Use of TNF blockers, including adalimumab-aaty, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy. Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV and closely monitor such patients for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, stop adalimumab-aaty and initiate effective antiviral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of adalimumab-aaty therapy in this situation and monitor patients closely. NEUROLOGIC REACTIONS Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of adalimumab-aaty in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of adalimumab-aaty should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders. HEMATOLOGIC REACTIONS Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Adverse reactions of the hematologic system, including medically significant cytopenia, have been infrequently reported with adalimumab products. Consider discontinuation of adalimumab-aaty therapy in patients with confirmed significant hematologic abnormalities. HEART FAILURE Cases of worsening congestive heart failure (CHF) and new-onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products. Exercise caution when using adalimumab-aaty in patients who have heart failure and monitor them carefully. AUTOIMMUNITY Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with adalimumab-aaty, discontinue treatment. IMMUNIZATIONS Patients on adalimumab-aaty may receive concurrent vaccinations, except for live vaccines. It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating adalimumab-aaty therapy. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products. The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. ADVERSE REACTIONS The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash. INDICATIONS Adalimumab-aaty is a tumor necrosis factor (TNF) blocker indicated for: Rheumatoid Arthritis (RA): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA Juvenile Idiopathic Arthritis (JIA): reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older Psoriatic Arthritis (PsA): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA Ankylosing Spondylitis (AS): reducing signs and symptoms in adult patients with active AS Crohn's Disease (CD): treatment of moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older Ulcerative Colitis (UC): treatment of moderately to severely active ulcerative colitis in adults Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers Plaque Psoriasis (Ps): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate Hidradenitis Suppurativa (HS): treatment of adult patients with moderate to severe hidradenitis suppurativa Uveitis (UV): treatment of non-infectious intermediate, posterior, and panuveitis in adult patients For Yuflyma (adalimumab-aaty): Please click for Full U.S. Prescribing Information. For adalimumab-aaty: Please see Full U.S. Prescribing Information. Globally, prescribing information varies; refer to the individual country product label for complete information. About Celltrion , Inc. Celltrion is a leading biopharmaceutical company that specializes in researching, developing, manufacturing, marketing and sales of innovative therapeutics that improve people's lives worldwide. Celltrion is a pioneer in the biosimilar space, having launched the world's first monoclonal antibody biosimilar. Our global pharmaceutical portfolio addresses a range of therapeutic areas including immunology, oncology, hematology, ophthalmology and endocrinology. Beyond biosimilar products, we are committed to advancing our pipeline with novel drugs to push the boundaries of scientific innovation and deliver quality medicines. For more information, please visit our website and stay updated with our latest news and events on our social media: LinkedIn, Instagram, X, and Facebook. About Celltrion USA Celltrion USA is Celltrion's U.S. subsidiary established in 2018. Headquartered in New Jersey, Celltrion USA is committed to expanding access to innovative biologics to improve care for U.S. patients. Celltrion's FDA-approved biosimilar products in immunology, oncology, hematology, and endocrinology include: INFLECTRA® (infliximab-dyyb), TRUXIMA® (rituximab-abbs), HERZUMA® (trastuzumab-pkrb), VEGZELMA® (bevacizumab-adcd), YUFLYMA®(adalimumab-aaty), AVTOZMA® (tocilizumab-anho), STEQEYMA® (ustekinumab-stba), STOBOCLO® (denosumab-bmwo), OSENVELT® (denosumab-bmwo) and OMLYCLO® (omalizumab-igec), as well as the novel biologic ZYMFENTRA® (infliximab-dyyb). Celltrion USA will continue to leverage Celltrion's unique heritage in biotechnology, supply chain excellence and best-in-class sales capabilities to improve access to high-quality biopharmaceuticals for U.S. patients. For more information, please visit and stay updated with our latest news and events on our social media: LinkedIn. FORWARD-LOOKING STATEMENT Certain information set forth in this press release contains statements related to our future business and financial performance and future events or developments involving Celltrion, Inc. and its subsidiaries that may constitute forward-looking statements under pertinent securities laws. This press release contains forward looking statements. These statements may be also identified by words such as "prepares", "hopes to", "upcoming", "plans to", "aims to", "to be launched", "is preparing", "once gained", "could", "with the aim of", "may", "once identified", "will", "working towards", "is due", "become available", "has potential to", "anticipate" the negative of these words or such other variations thereon or comparable terminology. In addition, our representatives may make oral forward-looking statements. Such statements are based on the current expectations and certain assumptions of Celltrion, Inc. and its subsidiaries' management, of which many are beyond its control. Forward-looking statements are provided to allow potential investors the opportunity to understand management's beliefs and opinions in respect of the future so that they may use such beliefs and opinions as one factor in evaluating an investment. These statements are not guarantees of future performance and undue reliance should not be placed on them. Such forward-looking statements necessarily involve known and unknown risks and uncertainties associated with the company's business, including the risk factors disclosed in its Annual Report and/or Quarterly Reports, which may cause actual performance and financial results in future periods to differ materially from any projections of future performance or results expressed or implied by such statements. Celltrion, Inc. and its subsidiaries undertake no obligation to update forward-looking statements if circumstances or management's estimates or opinions should change except as required by applicable securities laws. Trademarks Humira is a registered trademark of AbbVie. YUFLYMA® is a registered trademark of Celltrion, Inc., used under license. References [1] YUFLYMA US prescribing information (2023) [2] Lebwohl M et al., Pharmacokinetics, Efficacy and Safety after Multiple Switches from Reference Adalimumab to Adalimumab Biosimilar (CT-P17) in comparison with the Maintenance Group (Reference Adalimumab) in Patients with Moderate-toSevere Plaque Psoriasis: Week 27 Results from the Phase III Interchangeability Study. [EADV 2024, Poster number P0931]. Available at: [3] 9 Things to Know About Biosimilars and Interchangeable Biosimilars. Available at : For further information please contact:  Andria Arena [email protected] +1 516-578-0057 SOURCE Celltrion WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

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.