Helix BioMedix is developing novel, broad-spectrum, topical anti-infectives
for the treatment of skin and wound infections and the prevention of
Staphylococcus aureus (S. aureus) infections including those caused by
MRSA. These programs are based upon a first-in-class family of molecules
known as lipohexapeptides (or small molecule peptides) that we developed
to specifically combine the attributes of small molecule natural products
with the advantages of antimicrobial peptides. This new class of anti-infective
peptide has demonstrated significant improvement in activity, both in
vitro and in vivo, over traditional antimicrobial peptides.
As with traditional antimicrobial peptides, our lead lipohexapeptides (HB1345 and HB1275) are rapidly cidal, fail to engender resistance in vitro, are readily synthesized and do not exhibit cross-resistance with other antibiotics. However, these molecules also have the advantage of being more stable, safer and more cost-effective to manufacture than traditional antimicrobial peptides. In addition, primarily due to acylation (addition of a lipid), these molecules are significantly more active in complex biological environments such as serum or wound fluid. As a result, lipohexapeptides exhibit potent activity in animal infection models.
In pre-clinical testing our lead molecules exhibited broad-spectrum antimicrobial activity against significant bacterial pathogens such as S. aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa, and also pathogenic fungi such as Candida and Trichophyton species. This activity was maintained against antibiotic-resistant organisms such as MRSA and Vancomycin Resistant Enterococci. Our lead molecules have demonstrated significant activity in both bacterial and fungal animal infection models. In a S. aureus abraded skin infection model, our lead lipohexapeptides significantly reduced the number of bacteria following three days of once-daily dosing, and in many cases, our peptide eradicated the pathogen. In a guinea pig dermatophytosis model, our lead peptide candidates significantly reduced pathogen count and delivered clinical benefits comparable to Terbinafine, a drug approved by the FDA for onchomycosis. In both animal models, toxicity was not significantly different from that without peptides.