[Edaily Reporter YU JIN-HEE ] #HYUNDAI BIOSCIENCE CO., LTD. has demonstrated that niclosamide, the active ingredient in its broad-spectrum antiviral candidate “Zefti,” exhibits potent antiviral activity in human-derived tissues. This is expected to provide significant momentum to the “pre-confirmation preemptive administration respiratory basket clinical trial,” the first of its kind in the world.

HYUNDAI BIOSCIENCE CO., LTD. announced on the 30th that it confirmed the active ingredient in Jefti inhibited the proliferation of the influenza A (H1N1) virus by 99.2% in a three-dimensional (3D) alveolar organoid model derived from human embryonic stem cells.

This study was meticulously conducted at the Korea Preclinical Testing Support Center (KPEC) of the Korea Research Institute of Bioscience and Biotechnology as part of the Ministry of Science and ICT’s “National Preclinical Support System Project.” The research team infected 3D alveolar organoids with the influenza A virus (A/Korea/01/09) and then treated them with the test substance at various concentrations. When the relative expression level of HA mRNA—an indicator of viral replication—was measured on the third day post-infection, the average value in the untreated infected control group reached 12,858.439, whereas it plummeted to 101.692 in the group treated with the active ingredient in Jefty. KPEC officially determined that a significant viral inhibition effect of 99.2% was confirmed at that concentration.

Notably, the effective drug concentration of Jefti derived from this test perfectly matched the concentration ranges observed in previous animal efficacy tests for COVID-19 and H1N1, as well as in multiple respiratory virus tests conducted by the global contract research organization (CRO) Charles River. This demonstrates consistent antiviral activity across cells, animals, and human-derived tissues.

The fact that H1N1, COVID-19 (coronavirus), and dengue (flavivirus)—which have completely different genetic structures and replication mechanisms—are consistently inhibited within similar concentration ranges supports Jefti’s differentiated mechanism of action. This serves as quantitative evidence proving that the drug blocks host cell pathways commonly utilized by these viruses, rather than targeting the viruses themselves.

Previously, on the 22nd, HYUNDAI BIOSCIENCE CO., LTD. announced that it had received a “negative” genotoxicity result in a Good Laboratory Practice (GLP) micronucleus test and had established a No Observed Adverse Effect Level (NOAEL) through a 13-week repeated-dose toxicity study. With the planned clinical dose set within the NOAEL range, the concentration at which efficacy was confirmed in this organoid study aligns exactly with the dose range where safety has been established, thereby validating the clinical rationale.

Based on these results, HYUNDAI BIOSCIENCE CO., LTD. will launch the world’s first respiratory virus basket clinical trial (AIR-V) in the United States. Unlike previous antiviral clinical trials, which administered drugs after a confirmed diagnosis, this trial involves administering a single drug prior to confirmation—as soon as similar symptoms appear—and then evaluating its efficacy against COVID-19, influenza, and RSV individually based on the results.

This clinical trial design was personally proposed by Professor Davey Smith of the University of California, San Diego (UCSD), who serves as co-chair of the international protocol for the U.S. National Institutes of Health (NIH) ACTIV-2 study, and discussions are currently underway to officially launch the trial. Meanwhile, the Phase 2/3 clinical trial for dengue fever currently underway in Vietnam is also proceeding smoothly without any serious adverse events (SAEs).

Jin Geun-woo, CEO of HYUNDAI BIOSCIENCE CO., LTD., emphasized, “A universal antiviral drug cannot be realized by developing a new one every time the virus mutates,” adding, “Consistent effective drug concentrations must be confirmed even when conditions vary—such as in cells, animals, or human tissues—and these results are a key achievement that demonstrates that consistency.”

Bae Byung-jun, President of HYUNDAI BIOSCIENCE CO., LTD., said, “After receiving Professor Smith’s proposal, we scientifically verified the potential for success and decided to proceed with the clinical trial,” adding, “The safety data from the dengue fever clinical trial in Vietnam, the confirmation of no genotoxicity, and the results of this organoid study were all part of that thorough verification process.”