# A Novel Small Molecule for the Treatment of Periodontitis

> **NIH NIH R43** · VIRTICI, LLC · 2022 · $306,463

## Abstract

Project Summary
Our goal is to develop a first-in-class inhibitor of P. gingivalis colonization of oral biofilms as a treatment for
periodontitis. Severe periodontitis affects more than 11% of the world's population, resulting in billions of
dollars of direct and indirect costs to society, and is associated with a number of chronic conditions including
autoimmune, cardiovascular, respiratory, and neurodegenerative diseases1, 2, 4, 5, 7-9.
P. gingivalis is considered a causative species in periodontitis that can function to shape the overall microbial
community leading to dysbiosis and tissue damage10-13. Clinical research has confirmed that initial P. gingivalis
colonization occurs outside the subgingival pocket14-16. P. gingivalis adheres efficiently to supragingival
bacteria such as commensal streptococci17-19. This adherence modulates the pathogenic potential of P.
gingivalis and drives colonization20-22. Thus, inhibiting the adherence of P. gingivalis to supragingival bacteria
represents an excellent approach to reducing and preventing periodontitis.
Our project team originally discovered that initial colonization of the oral cavity by P. gingivalis is mediated by
the minor fimbrial antigen (Mfa1) of P. gingivalis binding to the surface antigen I/II of Streptococcus gordonii17,
23-25. Subsequently, we identified a domain in antigen I/II essential to this binding26, 27. A synthetic peptide
derived from this region, designated BAR, functions as a potent inhibitor of P. gingivalis adherence and
formation of biofilms26, 27. In addition, BAR demonstrates inhibition of P. gingivalis virulence by preventing
colonization and subsequent alveolar bone loss in mouse models of severe periodontitis20.
More recently, we have generated a lead small molecule mimetic of the BAR peptide (called PG95) to target P.
gingivalis in periodontitis. PG95 inhibits P. gingivalis colonization of biofilms and prevents bone loss in mouse
models of periodontitis, while showing no toxicity to human cells. The assessment of PG95 using in vitro
biofilm models and the mouse model of periodontitis has yielded clear potential as a treatment of periodontitis.
Based on these results, our goal is to develop a PG95 mouth rinse for the treatment and prevention of
periodontitis. This application is designed to develop quality control assays, define a formulation that is
transferable to human clinical trials, determine stability in serum and saliva, and demonstrate safety. The
specific aims are to: 1) synthesize PG95, develop a potency assay, and demonstrate efficacy in in vitro biofilm
models, 2) define an optimal formulation and determine in vitro PK for PG95, and 3) determine the maximum
tolerated dose (MTD) of PG95 following oral administration in mice. Completion of these studies will further
support the advancement of PG95 towards clinical development.

## Key facts

- **NIH application ID:** 10481054
- **Project number:** 1R43DE032770-01A1
- **Recipient organization:** VIRTICI, LLC
- **Principal Investigator:** Neil A Fanger
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $306,463
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481054

## Citation

> US National Institutes of Health, RePORTER application 10481054, A Novel Small Molecule for the Treatment of Periodontitis (1R43DE032770-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10481054. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*