Japanese Drug Targeting USAG-1 Completes Phase I Trial for Tooth Regrowth

Japanese researchers have completed the first-in-human clinical trial of a drug designed to regrow teeth by blocking the USAG-1 protein, bringing the concept of tooth regrowth medicine closer to reality. The therapy, known as TRG035, targets a protein that limits tooth formation in mice, and the team now plans to advance to Phase II trials in Japan with a goal of making the treatment available by 2030.

The scientific basis comes from a 2021 study published in Scientific Reports that showed local treatment aimed at USAG-1 could change tooth number in mice. Researchers found that the USAG-1 protein could limit the growth of teeth in mice, so ensuring that the protein didn't form could potentially invite teeth to grow. The team developed a medication to block the protein and successfully allowed mice to grow new teeth. A 2023 paper in Regenerative Therapy highlighted the anti-USAG-1 antibody work in mice as a possible breakthrough for treating human tooth anomalies, while a more recent 2026 review in Stem Cell Reviews and Reports kept the door open but used more cautious language.

The first-in-human study of TRG035 was a Phase I, single-dose, dose-escalation trial in 30 healthy adult men, ages 30 to under 65, each missing at least one molar. It tested five dose levels from 0.4 mg/kg to 24.0 mg/kg, with safety as the primary endpoint. Japan's national clinical-trials portal now lists the study as complete. The company behind the drug, Toregem BioPharma, has also said it completed the domestic Phase I study.

The initial target patient population is not adults who lost teeth to decay or trauma, but rather those with congenital tooth agenesis—especially severe congenital hypodontia or oligodontia, conditions in which people are born missing multiple permanent teeth. An investor-linked note from May 2026 described the initial rare-disease target as congenital absence of six or more permanent teeth, with a prevalence of about 0.1 percent of the population. Another statistic notes that about 1 percent of humans suffer from anodontia, a genetic condition that prevents a full set of teeth from growing.

The company's technology page suggests that if anti-USAG-1 is administered to the "third dental crest," it may be possible to grow a third tooth in adults. This idea is supported by research indicating that humans have the beginnings of a third set of teeth already embedded in their mouths, a phenomenon most visibly exhibited by the 1 percent of people with hyperdontia, who grow extra teeth.

In May 2026, Toregem announced roughly $5.3 million (¥850 million) in Pre-Series C financing and said its total funding, including grants and subsidies, had topped $29 million (¥4.6 billion). The company stated that the new money will support Phase II clinical trials of TRG035 in Japan and preparations for future U.S. development. While Toregem points to 2030 as a goal for practical use, it is a target, not a promise. Researchers still have to show that the drug can produce a properly placed, clinically useful human tooth that erupts, integrates, and functions without creating new problems.