TRG035 : Toregem BioPharma Anti-USAG-1 for Tooth Regeneration

Toregem BioPharma’s investigational antibody TRG035 has been designated an Orphan Medicinal Product by Japan’s
Ministry of Health, Labour and Welfare — a milestone step toward what could become the world’s first biological
treatment capable of stimulating natural tooth growth in patients with severe congenital hypodontia.

1. A Major Step for Dental and Regenerative Medicine

In a major step for dental and regenerative medicine, Toregem BioPharma Co., Ltd., a biotechnology company based
in Kyoto, announced that its investigational drug TRG035, an Anti-USAG-1 Antibody, has been
designated an Orphan Medicinal Product by Japan’s Ministry of Health, Labour and Welfare (MHLW). This recognition
moves the company closer to developing the world’s first biological treatment that stimulates natural tooth
growth in patients with severe congenital hypodontia — a rare condition that results in missing permanent teeth.

2. Understanding Severe Congenital Partial Anodontia

Severe congenital partial anodontia, also known as severe congenital hypodontia, occurs when six or more
permanent teeth fail to develop. The disorder affects far more than appearance — it can interfere with chewing,
speech, and the natural shape of the face. As a result, many patients struggle with daily activities, emotional
stress, and a reduced quality of life.

Today, treatment options remain limited to prosthetic solutions such as dentures, bridges, or dental implants.
Although these methods improve function and appearance, they do not treat the underlying problem: the lack of
natural tooth formation. No available therapy has been able to regenerate missing teeth caused by congenital or
acquired conditions. TRG035 may change that.

3. The Science Behind TRG035

TRG035 is the world’s first Anti-USAG-1 Antibody and marks a new direction in regenerative biology. The drug
targets USAG-1, a protein that acts as a natural inhibitor of tooth formation. When USAG-1 is suppressed,
previously inactive tooth buds can activate, allowing new teeth to grow.

Extensive preclinical studies support this mechanism. In animal models, the antibody triggered the eruption of
healthy, functional teeth — something once believed impossible in mammals. These findings created the foundation
for clinical development. Phase I trials are now underway in Japan to assess the drug’s safety and early signs
of effectiveness.

4. TRG035’s Recognition as an Orphan Drug: A Milestone

The Ministry of Health, Labour and Welfare granted TRG035 Orphan Medicinal Product status because it targets a
rare disease with no effective treatment. The designation provides several benefits, including:

• Tax incentives
• Financial aid
• Reduced regulatory fees
• Priority review

Together, these advantages will help speed up the drug’s development and shorten the timeline for patient access.

5. How TRG035 Works: Understanding USAG-1

To understand why the therapy is so promising, it helps to look at the role of USAG-1. The protein regulates
important biological pathways, including BMP and Wnt signaling, which are essential for tooth
development. When USAG-1 blocks these pathways, tooth germs fail to mature.

6. TRG035 Development Support and National Recognition

1. 2020 Toregem BioPharma Co., Ltd. founded as a spinout from Kyoto University.
2. June 2024 The Japan Agency for Medical Research and Development (AMED) selected TRG035 for the FY 2024 Venture Ecosystem Enhancement Project for Drug Discovery, titled “Development of a novel antibody drug to regenerate missing teeth in patients with congenital anodontia.”
3. Ongoing Phase I clinical trials underway in Japan to assess safety and early efficacy signals.

This support provides funding and strategic guidance that will help accelerate the drug’s progress, and
highlights the national importance of this research within Japan’s biomedical innovation landscape. The
government’s backing reflects a broader interest in advancing regenerative medicine and rare disease therapies.
For Toregem BioPharma, the support helps strengthen research momentum and opens the door to future international
collaboration.

7. Toregem BioPharma’s Vision for Tooth Regeneration

Toregem BioPharma Co., Ltd. was founded in 2020 as a spinout from Kyoto University. Under the leadership of CEO
Honoka Kiso, the company aims “to create a society where people are not afraid of losing their teeth.” Its work
builds on advanced research in molecular biology and supramolecular chemistry.

TRG035 is the company’s flagship product. It could be the first in a new category of regenerative antibody drugs
focused on repairing dental and craniofacial tissues rather than replacing them with prosthetics.

8. Future Possibilities: Beyond Congenital Tooth Loss

Although TRG035 is being developed for congenital hypodontia, Toregem BioPharma plans to investigate its use in
cases of acquired tooth loss. Injuries, aging, and periodontal disease cause millions of adults to lose teeth
every year. If the drug proves effective in those cases, it could reduce the need for dental implants and
transform everyday dental care worldwide.

Collaborations with international medical institutions are expected to support this expansion. In the long term,
the company hopes that the insights gained from TRG035 will also benefit other areas of regenerative medicine
influenced by BMP and Wnt pathways.

9. Significance for Global Oral Health

Tooth loss remains one of the most common chronic health conditions around the world. Its effects reach beyond aesthetics — missing teeth can impair nutrition, increase inflammation, and reduce overall quality of life. If TRG035 completes its clinical phases successfully, it could launch a new era of regenerative dentistry. This shift — from replacing teeth to regrowing them — aligns with global advances in personalized medicine and
biological therapies.

10. USAG-1 Research Reagents for Your Own Studies

If you’re researching BMP/Wnt signaling, tooth development biology, or USAG-1 (SOSTDC1) pathway mechanisms in your own lab, Dentinova supplies high-purity USAG-1 recombinant proteins and antigens to support your assays, antibody validation, and functional studies.

11. Frequently Asked Questions

12. Conclusion: The Beginning of Regenerative Dentistry

The development of TRG035 represents more than a scientific milestone. It signals the start of a new era in
regenerative dental treatment. By activating natural biological pathways, Toregem BioPharma aims to solve a
challenge that has affected humans throughout history: the inability to regrow lost teeth.

With an orphan drug designation, government support, and ongoing clinical trials, TRG035 is progressing quickly.
If its development continues to succeed, it may become the world’s first therapy capable of regenerating human
teeth — offering new hope to patients everywhere who struggle with congenital or acquired tooth loss.