The End of Dentures? World's First Tooth Regrowth Drug Enters Phase II Human Trials

For generations, losing a permanent tooth meant relying on mechanical replacements—dentures, bridges, or titanium implants drilled directly into the jawbone. But a fundamental shift from mechanical replacement to biological regeneration is now underway in laboratories across Japan.[3][5]

In June 2026, Japanese biotechnology startup Toregem BioPharma announced a $5.3 million funding round, pushing its total capital above $29 million. This financial milestone clears the runway for Phase II clinical trials of TRG-035, an experimental intravenous drug designed to stimulate the human body to regrow missing teeth.[1][2]

The transition to Phase II comes after the successful conclusion of Phase I safety trials, which ran from late 2024 through early 2026. Conducted at Kyoto University Hospital, the initial trial enrolled 30 healthy adult men aged 30 to 64, each of whom was missing at least one rear tooth.[2][6]

The primary goal of Phase I was to establish safety and dosing, not efficacy. As of early 2026, researchers reported no serious adverse events from the intravenous antibody, clearing the critical first hurdle for any novel therapeutic and allowing the team to begin analyzing the data for their final report.[2][4]

To understand how TRG-035 works, one must look at the biological brakes the human body applies to dental development. Humans naturally grow two sets of teeth: deciduous (baby) teeth and permanent adult teeth. However, researchers have long known that humans harbor the cellular potential for a "third set" of teeth in the form of dormant tooth buds hidden within the jaw.[1][3]

These buds remain dormant because of a specific protein called USAG-1 (uterine sensitization-associated gene-1). USAG-1 acts as a biological stop sign, suppressing the bone morphogenetic protein signaling pathway that normally drives tooth development and preventing the third set from ever emerging.[3][5]

TRG-035 is a monoclonal antibody engineered specifically to bind to and neutralize the USAG-1 protein. By temporarily removing this biological brake, the drug aims to "awaken" the dormant tooth buds, signaling the body's stem cells to resume the natural process of tooth formation.[1][6]

The foundational science behind this approach was cemented in a landmark 2021 study published in Science Advances. Researchers demonstrated that blocking USAG-1 in mice with congenital tooth agenesis allowed them to grow the teeth they were genetically missing. Subsequent trials in ferrets—animals with dental patterns remarkably similar to humans—yielded similarly positive results.[2][4]

While the ultimate dream is a treatment for general tooth loss, Phase II trials will target a highly specific population: patients with severe congenital hypodontia. This rare genetic condition is defined by the absence of six or more permanent teeth from birth.[1][6]

For children with severe hypodontia, the clinical stakes are immense. Because traditional dental implants cannot be safely placed until the jawbone finishes growing in late adolescence, children are often forced to rely on removable dentures for years. This can severely impact their nutrition, speech development, facial bone structure, and psychological well-being.[1][5]

The upcoming Phase II trial will administer the drug to patients with this condition, marking the first time researchers will actively look for signs of human tooth regeneration. If successful, the drug could offer these children a permanent, biological solution before they reach adulthood.[1][3]

Dr. Katsu Takahashi, the lead researcher and co-founder of Toregem BioPharma, has been explicit about the company's long-term roadmap. Once the drug is proven safe and effective for congenital conditions, the team plans to expand trials to adults with acquired tooth loss—those who have lost teeth to decay, gum disease, or trauma.[2][6]

The company has set an ambitious target of 2030 for regulatory approval and general availability for the hypodontia indication. Expanding the label to cover general adult tooth loss would likely take several years beyond that, requiring extensive, large-scale clinical trials across diverse global populations.[2][4]

Despite the excitement, dental professionals urge cautious optimism. Phase I trials only proved that the drug is safe, not that it actually regrows teeth in humans. The complex biomechanics of human jawbones, the precise alignment required for a functional bite, and the unpredictable nature of awakened stem cells all present significant clinical hurdles that animal models cannot fully replicate.[2][3]

Nevertheless, the initiation of Phase II trials represents a watershed moment in regenerative medicine. If TRG-035 fulfills its promise, the dental profession may eventually view titanium implants and acrylic dentures not as the standard of care, but as relics of a time before the body could be taught to heal itself.[3][5]