AvantGuard Receives $300K NIH Grant to Transform Fungal Skin Infection Treatment

We're pleased to announce that AvantGuard Inc. has been awarded a $300,000 Phase I grant from the National Institutes of Health to develop a novel treatment for dermatophytosis—the fungal infection responsible for conditions like ringworm, athlete's foot, and jock itch. This funding validates AvantGuard’s innovative approach to a widespread problem that affects millions and represents a global market exceeding $10 billion annually.

A Common Problem With Inadequate Solutions

Ringworm affects 20-25% of the global population.¹ Despite how widespread these infections are, they’ve been steadily increasing, in part because pharmaceutical companies have focused their resources on other pathogenic infections rather than fungi.²

Dermatophyte infections are notoriously difficult to eradicate completely, with recurrence rates as high as 25-40%.³ Why? Almost all current antifungal treatments are fungistatic, meaning they stop fungi from growing but don't actually kill them. This leaves the door open for infections to return.

The situation is getting worse. The CDC has recognized ringworm resistance as a significant and growing issue.⁴ Trichophyton rubrum, the most common fungus behind these superficial infections, is showing increasing resistance to terbinafine, including cases documented in the U.S.^5,6

Current treatment options fall into four main classes: azoles, allylamines, itraconazole, and terbinafine. The most widely used are over-the-counter topical treatments like clotrimazole and miconazole. While these have lower systemic toxicity than oral medications,⁷ they come with serious limitations: they're fungistatic rather than fungicidal, have poor skin permeability,⁸ and frequently cause burning, irritation, itching, or blistering.⁹

The results speak for themselves. While 80% of patients respond well to topical treatments, 20% develop chronic dermatophytosis that resists standard antifungal therapy.¹⁰ For these patients, what should be a straightforward infection becomes a persistent, frustrating condition with few good options.

New Threats

If the existing challenges weren't concerning enough, a new terbinafine-resistant dermatophyte is raising alarms worldwide. Trichophyton indotineae spreads person-to-person and causes inflammatory, intensely itchy infections that are often widespread, affecting the groin, gluteal region, trunk, and face.

First identified in India in 2020, T. indotineae has spread globally at an alarming pace, including documented cases in the U.S. The fungus developed resistance through point mutations in the squalene epoxidase gene, and oral treatment success rates across various antifungals have been disappointingly low.^11,12 The most common topical treatments show limited efficacy.¹³

This emergence of drug-resistant strains comes at a particularly troubling time. It has been over two decades since a new antifungal entered the market, with development largely stagnating since the late 1990s. Antifungal pipelines at major pharmaceutical companies are mostly nonexistent, as these companies have pivoted to high-profit drugs for chronic diseases instead.¹⁴

The gap between need and innovation is widening. We're facing a growing prevalence of invasive fungal infections, increasing resistance to existing treatments, persistent side effects that limit patient compliance, high recurrence rates, rising incidents of chronic infection, and a mounting burden on healthcare systems. The development of new antifungal drugs isn't just needed, it's urgent.

Our Solution

AvantGuard's polymer, polyvantoin chlorine, represents a fundamentally different approach to treating fungal skin infections. Just as povidone stabilizes iodine to create the widely trusted antiseptic povidone-iodine (PVP-I), our polymer stabilizes chlorine to create a biocompatible, broad-spectrum antifungal with a critical advantage: there's no history of organisms developing chlorine resistance.

Our polymer combines a chloramine with an N-halamine monomer (Avantamine™) and hydrophilic monomers to create a truly fungicidal treatment. Unlike the fungistatic antifungals currently dominating the market, polyvantoin chlorine uses oxidative chemistry to rapidly kill even antifungal-resistant pathogens.

The early results are promising. Polyvantoin chlorine achieved total biofilm eradication in 24 hours against mature C. albicans biofilms. When compared head-to-head with clotrimazole (one of the most common over-the-counter treatments), polyvantoin chlorine demonstrated superior effectiveness against C. albicans biofilms developed over 72 hours in ex vivo testing, with similar efficacy in vivo studies.

Preliminary Data

Our Phase I grant is supported by compelling preliminary data demonstrating both safety and efficacy. Acute dermal irritation testing in a rabbit model showed no irritation at concentrations up to 2.4% (approximately 24,000 ppm chlorine) with 4-hour contact times, establishing a strong safety profile for topical use.

Efficacy testing revealed polyvantoin chlorine performs as a true fungicidal agent, not just fungistatic. Our polymer matched the antimicrobial performance of hypochlorous acid (a powerful industrial disinfectant) against C. albicans, T. mentagrophytes, and A. brasiliensis, while offering superior stability. In biofilm eradication studies (the gold standard for evaluating persistent infections), our polymer achieved complete kill of mature C. albicans biofilms at concentrations below 2,000 ppm after 24 hours. When formulated as a hydrogel and tested head-to-head against 1% clotrimazole and 1% silver sulfadiazine (current standard treatments), our formulation demonstrated superior efficacy with consistent, concentration-dependent performance.

Perhaps most importantly, polyvantoin chlorine offers practical advantages that existing treatments lack: years of shelf-life in solid form, significantly lower corrosivity than other chlorinated compounds, and no staining of fabric or skin. These characteristics, combined with the absence of resistance development to chlorine-based treatments, position our polymer as a genuinely differentiated solution to a growing clinical need.

What This Funding Enables

This $300,000 NIH grant will support three critical development aims:

Aim 1: Material Development – We'll optimize our polymer synthesis process to ensure batch-to-batch consistency, verify broad-spectrum fungicidal efficacy across both drug-resistant and non-resistant fungal strains (including multiple Trichophyton and Candida species), and refine our hydrogel formulation for clinical testing.

Aim 2: In Vivo Efficacy Testing – Using an established porcine wound model (the gold standard for human skin testing), we'll evaluate our hydrogel's ability to prevent and reduce Trichophyton rubrum and Trichophyton interdigitale biofilms at various concentrations, benchmarking performance against current market leaders miconazole and clotrimazole.

Aim 3: Safety Validation – We'll conduct formal dermal irritation testing of our hydrogel formulation following EPA and OECD protocols to confirm the safety profile established in our preliminary liquid studies, testing both standard 4-hour and extended 24-hour exposure periods.

Looking Ahead

This Phase I grant represents an important first step in bringing a truly novel antifungal to market. Over the coming months, we'll demonstrate the efficacy and safety of our polymer against the most challenging fungal pathogens, including drug-resistant strains that are spreading globally. While we're initially testing a hydrogel formulation, we're already exploring alternative formats, such as creams or ointments, that may offer superior skin penetration and patient experience for commercial launch.

Success in Phase I will pave the way for Phase II development, which will include the comprehensive pharmacology, toxicology, and safety studies required for an Investigational New Drug (IND) application and subsequent clinical trials. With no new antifungal entering the market in over two decades and resistance continuing to spread, the need for innovation has never been more urgent.

We're grateful to the NIH for recognizing the potential of this approach and excited about the path ahead. The versatility of Avantamine chemistry, which is already demonstrating promise in both surface disinfection and now topical therapeutics, positions us to address multiple facets of the growing antimicrobial resistance crisis.

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References

1. Faway E, Cambier L, De Vuyst E, et al. Responses of Reconstructed Human Epidermis to Trichophyton rubrum Infection and Impairment of Infection by the Inhibitor PD169316. J Invest Dermatol. Oct 2019;139(10):2080-2089.e6. doi:10.1016/j.jid.2019.03.1147

2. Hendrickson JA, Hu C, Aitken SL, Beyda N. Antifungal Resistance: a Concerning Trend for the Present and Future. Curr Infect Dis Rep. Nov 16 2019;21(12):47. doi:10.1007/s11908-019-0702-9

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4. CDC. Antimicrobial-Resistant Fungal Diseases. March 19, 2025 

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10. Blutfield MS, Lohre JM, Pawich DA, Vlahovic TC. The immunologic response to Trichophyton rubrum in lower extremity fungal infections. Journal of fungi. 2015;1(2):130-137. 

11. Uhrlaß S, Verma SB, Gräser Y, et al. Trichophyton indotineae—an emerging pathogen causing recalcitrant dermatophytoses in India and worldwide—a multidimensional perspective. Journal of Fungi. 2022;8(7):757. 

12. Gawaz A, Nenoff P, Uhrlaß S, Schaller M. Therapie eines Terbinafin-resistenten Trichophyton mentagrophytes Typ VIII. Der Hautarzt. 2021;72(10):900-904. 

13. Khurana A, Savitha S, Sardana K, Chowdhary A. Clinico-mycological and therapeutic updates on tinea corporis/cruris in the era of Trichophyton indotineae. Journal of the American Academy of Dermatology. 2024;

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