Kyoto drug enters human trials to regrow teeth, may replace implants by 2030

A tooth-regrowth drug has moved out of the mouse lab and into people. At Kyoto University Hospital, researchers began the first human test of an anti-USAG-1 antibody designed to block a protein that suppresses tooth development, putting one of dentistry’s most unusual regeneration projects into Phase I study.

The experimental medicine, TRG035 from Toregem BioPharma, targets congenital tooth agenesis, also described as congenital edentulism or severe congenital hypodontia. That rare hereditary condition affects about 1 in 1,000 people, and it is the first indication the Kyoto group chose because the biological target is clear: if USAG-1 is blocked, the body may be able to form a tooth that never developed in the first place.

The first-in-human trial was announced for September 2024 and later reported as having begun in October 2024. It reportedly enrolled 30 adult men, ages 30 to 64, each missing at least one tooth. The purpose of this stage is safety and dosage, not proof that new teeth will actually grow. That matters because the leap from animal regeneration to reliable human dental therapy is still enormous, especially when durability, function and long-term safety have not yet been shown.

The program grew from Kyoto University research that first linked USAG-1 blockade to tooth regeneration in mice. In a 2021 Science Advances paper, Kyoto University researchers and collaborators reported that blocking USAG-1 function through knockout or antibody treatment relieved congenital tooth agenesis in mice. Follow-up animal work in other mammals, including ferrets, strengthened the case that the approach could eventually generate functional teeth rather than just tissue fragments.

Katsu Takahashi, who has long led the project, has described the treatment as a possible third option alongside dentures and implants, not simply a more convenient version of the same thing. Toregem BioPharma has also said its anti-USAG-1 antibody received orphan-drug designation in Japan for severe congenital hypodontia, a step that can bring tax incentives, grant support and prioritized review from the Ministry of Health, Labour and Welfare. The company and researchers have pointed to commercialization around 2030, but that goal still depends on human data that has yet to arrive. For dentistry, the real milestone is not a headline about replacing implants. It is whether a suppressed tooth program can be safely switched back on in people, one trial at a time.