[Edaily Reporter YU JIN-HEE ] #HYUNDAI BIOSCIENCE CO., LTD. announced on the 22nd that it has confirmed cytological safety data by obtaining a final “negative” result for genotoxicity in a GLP-compliant micronucleus test conducted by an accredited nonclinical testing facility.

This study is one of several key preclinical trials conducted to scientifically demonstrate the toxicological integrity required to meet the standards of global regulatory agencies. It was carried out after Professor David Smith of the University of California, San Diego (UCSD) School of Medicine—who previously served as the Chair of the U.S. National Institutes of Health (NIH) government-funded new drug development clinical trial (ACTIV-2)—proposed the respiratory virus basket clinical trial (AIR-V). HYUNDAI BIOSCIENCE CO., LTD. plans to combine this preclinical data with clinical records from its dengue fever trial in Vietnam to begin negotiations on the final timeline for initiating the U.S. clinical trial.

The “host cell-targeting mechanism,” which is effective regardless of viral mutations, has been recognized as a promising alternative for the development of universal antiviral drugs; however, existing research compounds have faced difficulties in commercialization because they have been unable to overcome genotoxic limitations that cause damage to human cells or disrupt genomic structure. Through this in vivo subnuclear assay, JEFT successfully demonstrated the efficacy of this mechanism from a regulatory science perspective, thereby resolving the toxicological challenges.

This study was conducted at the DT&CRO CO., Ltd., an accredited nonclinical testing facility, in accordance with the notices of the Ministry of Food and Drug Safety and the guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). A quantitative assessment of micronucleus formation—which results from chromosomal abnormalities following administration of the test substance—revealed that the “frequency of micronucleated erythrocytes,” a key indicator of genotoxicity, was ultimately determined to be negative in all dose groups, including the highest dose group, with no statistically significant difference compared to the negative control group.

In particular, a detailed quantitative analysis of the toxicological data revealed that the Maximum Tolerated Dose (MTD) of 1,000 mg/kg/day used in the study corresponds to approximately 9,677 mg per day for an adult (based on a 60 kg body weight) when converted to a Human Equivalent Dose (HED). This represents a 7.17-fold increase compared to the maximum planned clinical dose to be administered to patients, constituting a severe test condition; it was quantitatively demonstrated that the drug does not induce alterations in cellular genetic structure even under such extreme dosing conditions.

Through a previously completed 13-week repeated-dose long-term toxicity study, the company established a No Observed Adverse Effect Level (NOAEL) and set the maximum clinical dose at a level 5.93 times lower than this standard (providing a safety margin of approximately 6 times). Thus, by simultaneously demonstrating both systemic toxicity safety and genetic integrity, the company has established a high level of dual safety assurance.

Jin Geun-woo, CEO of HYUNDAI BIOSCIENCE CO., LTD., emphasized, “These results mark the overcoming of the biggest toxicological hurdle toward entering a U.S. Phase 2 clinical trial for respiratory viruses,” adding, “By proving that Jefti selectively blocks only the viral replication pathway while firmly maintaining the structural integrity of the host cell’s chromosomes, we have scientifically validated the safety of its host-targeted mechanism.”

With the “genetic safety evidence” required for the safe, preemptive administration of the drug to symptomatic patients prior to a confirmed diagnosis now firmly established, the likelihood of success for the upcoming U.S. respiratory virus basket clinical trial—as well as the probability of regulatory approval—has significantly increased. This clinical trial is the world’s first clinical model to immediately treat multiple respiratory diseases—including COVID-19, influenza, and RSV—at the early symptom stage (cough, fever, etc.) without the need for separate confirmatory testing. Just as penicillin revolutionized the treatment of infectious diseases by exerting broad-spectrum antibacterial effects upon the onset of early symptoms—regardless of the causative strain—Zefti has now secured the core momentum to serve as a universal antiviral drug capable of simultaneously controlling multiple respiratory viruses with a single medication.

Bae Byung-jun, President of HYUNDAI BIOSCIENCE CO., LTD., emphasized, “The U.S. respiratory virus basket trial marks a major turning point in infectious disease treatment by simultaneously addressing multiple respiratory diseases with a single drug,” adding, “The scientific data obtained from this trial will serve as a key foundation that firmly supports the potential for success and commercial value of basket trials that simultaneously control multiple respiratory viruses.”