The dated record

1. 2009-08-03

   Functional bioengineered tooth replacement in an adult mouse

   Bioengineered tooth germ (organ germ transplant) T2 · Animal result

   • Ikeda E, Morita R, Nakao K, et al. (2009). Fully functional bioengineered tooth replacement as an organ replacement therapy. Proceedings of the National Academy of Sciences 106(32):13475-13480.
2. 2021-02-12

   Anti-USAG-1 antibody rescues tooth agenesis in mouse models (Science Advances)

   Anti-USAG-1 antibody (TRG-035) T2 · Animal result

   • Murashima-Suginami A, Kiso H, Tokita Y, et al. (2021). Anti-USAG-1 therapy for tooth regeneration through enhanced BMP signaling. Science Advances 7(7):eabf1798.
3. 2024-05-03

   Phase I first-in-human study of TRG-035 announced and registered (Kitano Hospital)

   Anti-USAG-1 antibody (TRG-035) T3 · Small or narrow human data

   • Kitano Hospital / Toregem BioPharma (2024). First-in-human Phase I study of TRG-035 (anti-USAG-1 antibody): trial announcement and registry record , single ascending dose, adult participants. Kitano Hospital trial announcement, 3 May 2024.
4. 2024-11-27

   Chemically defined culture supports mouse tooth reconstitution and BMP-driven enamel induction

   Bioengineered tooth germ (organ germ transplant) T2 · Animal result

   • Zhang Z, Hu H, Xu Z, et al. (2024). A chemically defined culture for tooth reconstitution. Advanced Science 12(3):e2404345.
5. 2025-01-21

   Inductive tooth germ secretome and extracellular vesicles shift epithelial signaling but do not replace living mesenchyme for tooth induction

   Bioengineered tooth germ (organ germ transplant) T1 · In vitro / mechanism

   • Birjandi AA, Sharpe PT (2025). The Secretome of the Inductive Tooth Germ Exhibits Signals Required for Tooth Development. Bioengineering 12(2):96.
6. 2025-02-11

   Decellularized tooth-bud scaffolds seeded with dental and endothelial cells form tooth-like tissues in adult minipigs

   Bioengineered tooth germ (organ germ transplant) T2 · Animal result

   • Zhang W, Yelick PC (2025). In vivo bioengineered tooth formation using decellularized tooth bud extracellular matrix scaffolds. Stem Cells Translational Medicine 14(2):szae076.
7. 2025-09-29

   TRG-035 receives Japanese orphan drug designation for severe congenital partial anodontia

   Anti-USAG-1 antibody (TRG-035)

   • AMED / Toregem BioPharma (2025). TRG-035 receives Japanese orphan drug designation for severe congenital partial anodontia. AMED record, 29 September 2025.
8. 2025-10-09

   Lingual-buccal positional memory persists in dissociated mouse dental mesenchyme

   Bioengineered tooth germ (organ germ transplant) T2 · Animal result

   • Kim EJ, Kim HY, Lee S, et al. (2025). Prespecified dental mesenchymal cells for the making of a tooth. International Journal of Oral Science 17:67.
9. 2025-11-04

   Biomimetic elastin-like matrix rebuilds enamel structure and mechanical properties on human tooth sections

   Dental epithelial organoids T1 · In vitro / mechanism

   • Hasan A, Chuvilin A, Van Teijlingen A, et al. (2025). Biomimetic supramolecular protein matrix restores structure and properties of human dental enamel. Nature Communications 16:9434.
10. 2026-02-01

    USAG-1 expression mapped to gingival fibroblast and epithelial subsets in review

    Anti-USAG-1 antibody (TRG-035)

    • Moradi Z, Karimi M, Kolahdouz S, et al. (2026). USAG-1 in tooth regeneration: a review of BMP and Wnt signaling, gingival single-cell expression, and the TRG-035 clinical timeline. Clinical and Experimental Dental Research 12(1):e70301.
11. 2026-03-01

    Human iPSCs induced to PITX2-positive embryonic oral epithelium in 10 days

    Dental epithelial organoids T1 · In vitro / mechanism

    • Nakashima K, Tanaka J, Matsuno E, et al. (2026). Development of a high-efficiency induction system for embryonic oral epithelium from human pluripotent stem cells. Stem Cell Reports 21(3):103779.
12. 2026-03-02

    Soluble Notch agonist matures human ameloblast organoids and produces enamel-like mineral in mice

    Dental epithelial organoids T2 · Animal result

    • Patni AP, Mout R, Alghadeer A, et al. (2026). Soluble Notch agonist enables human ameloblast maturation and enamel-like tissue formation for tooth regeneration. International Journal of Oral Science 18:67.
13. 2026-05-03

    Small randomized trial reports borderline dentin-bridge volume increase with PRF versus MTA in direct pulp capping

    Pulp and dentine repair (DPSC/SHED grafts, small molecules) T3 · Small or narrow human data

    • Asthana G, Tamuli R, Manglani S, et al. (2026). Comparative Evaluation of Platelet-Rich Fibrin and Mineral Trioxide Aggregate in the Direct Pulp Capping of Carious Exposures: A Randomized Clinical Trial. Cureus 18(5):e108203.
14. 2026-05-19

    Sponsor reports Phase I dosing complete; Pre-Series C financing disclosed for Phase II

    Anti-USAG-1 antibody (TRG-035) T4 · Human efficacy or safety, single programme

    • Toregem BioPharma (2026). Pre-Series C financing and Phase II preparation disclosure; sponsor reports Phase I dosing complete. Company disclosure, 19 May 2026.
15. 2026-07-28

    MRI/CT imaging biomarkers proposed as surrogate endpoints for TRG-035 pediatric trials (ferret study)

    Anti-USAG-1 antibody (TRG-035)

    • Murashima-Suginami A, Ishimori T, Sawada T, Takamine A, Kiso H, Ohshima H, et al. (2026). Imaging biomarkers as surrogate endpoints for clinical trials on permanent tooth regeneration in congenital tooth agenesis. Journal of Oral Biosciences 68(3):100775.
16. 2026-08-07

    Size scaling disrupts layered mineral pattern in tooth root organoids

    Tooth root organoids / whole-tooth reassociation T2 · Animal result

    • Calabrese TC, Rothermund K, Syed FNP, et al. (2026). Effects of size scaling on cellular dynamics and tissue patterning in tooth root organoids. Frontiers in Bioengineering and Biotechnology 14:1801110.
17. 2026-08-17

    PMDA clinical trial notification investigation completed for TRG-035 Phase IIa

    Anti-USAG-1 antibody (TRG-035)

    • Toregem BioPharma (2026). Announcement for Completion of the PMDA Investigation of CTN (Clinical Trial Notification) for TRG035 Phase IIa Trial. Company disclosure, 17 August 2026.