Antimicrobial Orynotides: new agents for treatment of infections caused by multiple-drug resistant pathogens

The growing threat of antibiotic resistant bacterial and fungal pathogens requires new paradigms for addressing the worldwide threat of “superbugs.” These infectious agents have adapted to acquire resistance, in some cases, to all known antibiotics, opening up the real possibility of devastating epidemics.

Multi-drug resistant (MDR) pathogens represent an immediate danger to individuals and populations. Engineered Orynotides are highly effective in killing MDR bacteria in the test tube and in animal models. Moreover, sequential passage of these pathogens in Orynotide preparations fails to select for resistance to these novel peptide drugs.


Orynotides defeat a broad spectrum of dangerous bacteria and fungi without creating resistance

Therapeutic efficacy of several Orynotides has been demonstrated in animal models of bacterial and polymicrobial systemic infection. The unique mode of action limits the potential for emergence of Orynotide resistance. The peptides are selective, sparing the host, and in fact enhance microbial clearance by the host. Oryn has demonstrated that Orynotides are:

  • Bactericidal against methacillin-resistant Staphylococcus aureus (MRSA), antibiotic resistant Pseudomonas species, and the recently isolated CRE (carbapenem resistant) superbugs.
  • Antifungal Orynotides are microbicidal against several multi-drug resistant strains of Candida albicans.
  • Engineered Orynotides are first-in-class agents with the potential for treatment of sepsis, a truly unmet need. There are currently no approved drugs for this disorder, which is lethal in one-third of all patients with this diagnosis.

Orynotides as therapeutics for sepsis

Sepsis is the body’s overwhelming and life-threatening response to an infection which can lead to tissue damage, organ failure, and death. These clinical responses often occur very quickly.

Orynotides are derived from theta defensins, peptides believed to confer sepsis resistance to Old World monkeys. Oryn has shown that these engineered Orynotides are effective in mouse models of polymicrobial sepsis and sepsis mediated by E.coli, Staphylococcus aureus, and carbapenem resistant (CRE) Klebsiella pneumoniae.


Severe sepsis was surgically induced in mice. Four hours after surgery, mice were treated with saline or a single injection of OTP-300. Treatment with OTP-300 resulted in dramatic improvement of survival compared to the saline-treated cohort, 90% of which were dead by day 5.