AvantGuard Awarded $350K NIH Grant to Combat Diabetic Foot Ulcer Infections

We're pleased to announce that AvantGuard Inc. has been awarded a $350,000 Phase I grant from the National Institutes of Health to develop an antimicrobial treatment for diabetic foot ulcers—one of the most challenging and costly complications of diabetes care.

A Persistent Challenge in Wound Care

Diabetic foot ulcers (DFUs) are microvascular lesions resulting from peripheral arterial disease, bone abnormalities, diabetic neuropathy, and other predisposing factors. Approximately 15-25% of diabetic patients will develop foot ulcerations over their lifetime, and a quarter of these become chronic wounds that carry significant amputation risk.^1,2

What makes these ulcers particularly difficult to manage is the frequency and persistence of infection. Between 40-80% of diabetic foot ulcers become infected, representing a major cause of morbidity and mortality.^3,4 As many as half of all DFUs are already infected at the time patients seek clinical care, and up to 25% of adults with infected diabetic foot ulcers experience persistent infection for 10-20 days despite treatment.^5,6

The human and economic toll is substantial. Ulcer care alone adds $9-13 billion yearly to costs associated with diabetes, with individual patients facing expenses reaching $58,000 annually.^7,8 Beyond these direct costs, the impact on quality of life and the risk of limb loss make effective infection control a critical unmet need.

Why Current Treatments Fall Short

The challenge in treating DFU infections stems from three fundamental barriers: the heterogeneity of pathogens involved, increasing antimicrobial resistance, and the severity of the wounds themselves.⁹ Despite numerous products on the market, wound dressings and wound washes containing antimicrobials have not demonstrated clinical superiority over those without antimicrobial agents.¹⁰

This gap between available products and clinical outcomes reveals the need for a fundamentally different approach—one that can handle diverse pathogens, avoid resistance generation, and remain effective in the challenging environment of a chronic wound.

Polyvantoin chlorine: Combining Immune System Chemistry with Polymer Stability

Our solution combines two proven elements in a novel way: the oxidative chemistry our immune system naturally uses, enhanced by an inert halogen-stabilizing polymer.

The concept parallels how povidone polymer stabilizes iodine to create povidone-iodine (PVP-I), improving efficacy, stability, and safety. We've developed a chloramine monomer called Avantamine™ that stabilizes chlorine (a more biocompatible halogen than iodine). Our neutrophils already use chlorine-based chemistry, converting salt in bodily fluids into hypochlorous acid and taurine chloramine to fight infections.^11-13

Taurine chloramine has been clinically evaluated as an antiseptic and shown promise, but its instability outside the body has limited practical application.¹² Avantamine addresses this limitation. When co-polymerized with monomers that improve hydrophilicity, it creates polyvantoin chlorine—a stable polymer that can be formulated as a powder, liquid, or hydrogel. The result is an antiseptic that's highly effective and safe while being long-lasting and unlikely to generate resistance.

Strong Preliminary Data

Our preliminary testing demonstrates polyvantoin chlorine's potential across multiple models relevant to diabetic foot ulcer care.

Biofilm eradication studies in vitro showed that 0.6% polyvantoin chlorine achieved higher log reduction compared to povidone-iodine, polyhexamethylene biguanide (PHMB), and chlorhexidine. Ex vivo porcine biofilm models demonstrated better efficacy than silver sulfadiazine and triple antibiotic ointment against bacteria, and superior performance compared to clotrimazole against fungi.

A murine model showed polyvantoin chlorine's superiority to chlorhexidine and striking efficacy against Candida auris, which is a notoriously difficult pathogen to eliminate. Perhaps most relevant to this grant, a pilot trial using an in vivo porcine wound model demonstrated that polyvantoin chlorine outperformed both PVP-I and PHMB against biofilms of Pseudomonas aeruginosa and Staphylococcus aureus, as well as exceeding clotrimazole and miconazole against Trichophyton rubrum biofilms in wounds.

Safety has been thoroughly evaluated across multiple studies. Histological testing after porcine studies showed results similar to untreated wounds and clotrimazole. A rabbit model showed no skin irritation at concentrations up to 3.6%, and a murine decolonization model showed no irritation at 1.2% applied daily. Minimum inhibitory concentration testing revealed consistent efficacy against several common antimicrobial-resistant bacterial and fungal strains.

Polyvantoin chlorine also demonstrates unique practical advantages: it retains 60% of active chlorine after 24 hours on porcine tissue, shows substantial resistance to neutralization from simulated wound fluid, causes no corrosion of steel or degradation of plastic at high concentrations, and maintains excellent heat-tolerant stability.

The Development Plan

This Phase I grant will support two integrated aims focused on bringing polyvantoin chlorine toward clinical application:

Aim 1: Product Development – We will continue to develop our formulations (AvantSept and AvantGel), testing additive packages, and viscosity adjustments. We will also streamline our manufacturing processes to prepare for pre-clinical testing.

Aim 2: Definitive Animal Model – We'll manufacture polyvantoin chlorine in our laboratory while developing rigorous process controls, then test AvantGel and AvantSept against Pseudomonas aeruginosa and Staphylococcus aureus in an in vivo biofilm eradication porcine model. This work will be conducted under the supervision of Dr. Stephen Davis at the University of Miami, with histological analysis on all animals in statistically sufficient numbers. We'll benchmark our performance against Prontosan (PHMB) wash and gel.

Addressing a Critical Need

Diabetic foot ulcers represent a convergence of clinical challenge and human impact. Patients face not only the immediate burden of chronic wounds and recurrent infections but also the ever-present threat of amputation. Healthcare systems struggle with the substantial costs, while current treatments offer limited solutions.

Polyvantoin chlorine's combination of broad-spectrum efficacy, biocompatibility, stability in wound environments, and lack of resistance generation addresses the core limitations that have hindered existing antimicrobial wound treatments. The 510(k) regulatory pathway offers a more direct route to clinical availability compared to traditional drug development.

This NIH grant enables us to generate the definitive animal model data and complete the pre-clinical safety testing necessary to advance toward FDA clearance. We're working to provide clinicians with a tool that can genuinely improve outcomes for diabetic patients facing one of the most difficult complications of their disease.

Read the Full Press Release

---

References

References

(1) Neville, R. F.; Kayssi, A.; Buescher, T.; Stempel, M. S. The diabetic foot. Curr Probl Surg 2016, 53 (9), 408–437. DOI: 10.1067/j.cpsurg.2016.07.003  From NLM.

(2) Lin, C.; Liu, J.; Sun, H. Risk factors for lower extremity amputation in patients with diabetic foot ulcers: A meta-analysis. PLoS One 2020, 15 (9), e0239236. DOI: 10.1371/journal.pone.0239236  From NLM.

(3) FDA. FDA warns about rare but serious allergic reactions with the skin antiseptic chlorhexidine gluconate. Drug Safety Communications 2017.

(4) Maillard, J. Y.; Pascoe, M. Disinfectants and antiseptics: mechanisms of action and resistance. Nat Rev Microbiol 2024, 22 (1), 4–17. DOI: 10.1038/s41579-023-00958-3  From NLM.

(5) McDermott, K.; Fang, M.; Boulton, A. J. M.; Selvin, E.; Hicks, C. W. Etiology, Epidemiology, and Disparities in the Burden of Diabetic Foot Ulcers. Diabetes Care 2023, 46 (1), 209–221. DOI: 10.2337/dci22-0043  From NLM.

(6) Ndosi, M.; Wright-Hughes, A.; Brown, S.; Backhouse, M.; Lipsky, B. A.; Bhogal, M.; Reynolds, C.; Vowden, P.; Jude, E. B.; Nixon, J.; et al. Prognosis of the infected diabetic foot ulcer: a 12-month prospective observational study. Diabet Med 2018, 35 (1), 78–88. DOI: 10.1111/dme.13537  From NLM.

(7) Crnich, C. J.; Pop-Vicas, A. E.; Hedberg, T. G.; Perl, T. M. Efficacy and safety of a novel antimicrobial preoperative skin preparation. Infect Control Hosp Epidemiol 2019, 40 (10), 1157–1163. DOI: 10.1017/ice.2019.200  From NLM.

(8) Hicks, C. W.; Selvarajah, S.; Mathioudakis, N.; Sherman, R. E.; Hines, K. F.; Black, J. H., 3rd; Abularrage, C. J. Burden of Infected Diabetic Foot Ulcers on Hospital Admissions and Costs. Ann Vasc Surg 2016, 33, 149–158. DOI: 10.1016/j.avsg.2015.11.025  From NLM.

(9) Kavitha, K. V.; Tiwari, S.; Purandare, V. B.; Khedkar, S.; Bhosale, S. S.; Unnikrishnan, A. G. Choice of wound care in diabetic foot ulcer: A practical approach. World J Diabetes 2014, 5 (4), 546–556. DOI: 10.4239/wjd.v5.i4.546  From NLM.

(10) Wang, H.; Chediak, J. A.; Belmont, P. J.; Saylor, D. M.; Phillips, K. S. Preclinical performance testing of medical devices with antimicrobial effects. Nature Reviews Bioengineering 2023, 1 (8), 589–605. DOI: 10.1038/s44222-023-00060-6.

(11) Nagl, M.; Nguyen, V.; Gottardi, W.; Ulmer, H.; Höpfl, R. Tolerability and efficacy of N‐chlorotaurine in comparison with chloramine T for the treatment of chronic leg ulcers with a purulent coating: a randomized phase II study. British Journal of Dermatology 2003, 149 (3), 590–597.

(12) Anich, C.; Orth‐Höller, D.; Lackner, M.; Nagl, M. N‐chlorotaurine, a potent weapon against multiresistant bacteria. Journal of Applied Microbiology 2021, 131 (4), 1742–1748.

(13) Gottardi, W.; Nagl, M. N-chlorotaurine, a natural antiseptic with outstanding tolerability. Journal of antimicrobial chemotherapy 2010, 65 (3), 399–409.