First-in-Human Trial for Novel Antibacterial Peptide

An antibacterial peptide which is intended to be used for the treatment of prosthetic joint infections (PJI) has just completed its first-in-human trial.

According to the study sponsor, Pittsburgh, Pennsylvania-based biotech company Peptilogics, Inc., the peptide—PLG0206—was well tolerated in healthy volunteers.

“The safety, tolerability, and pharmacokinetics observed in this Phase 1 study of PLG0206 intravenously administered is an important milestone for Peptilogics as we come one step closer to providing this potential treatment to prosthetic joint infection patients and the orthopedic and infectious disease communities,” said Jonathan Steckbeck, Ph.D., Founder and CEO of Peptilogics.

According to Peptilogics, “PLG0206 is an investigational, potent, broad-spectrum antibacterial peptide that has been granted FDA Orphan Drug Designation and Qualified Infectious Disease Product Designation for the treatment of prosthetic joint infection.”

There were 47 participants in this Phase 1 study (6 cohorts of 8 participants receiving escalating single IV infusions of PLG0206 1 mg/kg dose or placebo). Eight participants per cohort were randomized 3:1 to receive either PLG0206 (6 per cohort) or placebo (2 per cohort).

“The systemic safety and tolerability data from our first-in-human trial of PLG0206 intravenously administered are highly encouraging and will inform dosing regimens in future studies of PLG0206 in prosthetic joint infection and other indications,” said. “We remain on track to initiate a first-in-patient clinical study for the treatment of prosthetic joint infection in the first quarter of 2022.”

David Huang, M.D., Ph.D., and chief medical officer of Peptilogics told OTW, “PLG0206 is an investigational, rapidly bactericidal, broad-spectrum anti-infective peptide with potent anti-biofilm activity being developed for rare orthopedic infections. We are currently evaluating its potential in periprosthetic joint infections, a serious complication occurring from joint replacement surgery. PLG0206 has a unique mechanism of action that directly acts on the biofilm-producing bacteria and persistent pathogens that can evade conventional antibiotics, targeting and disrupting bacterial membranes to trigger bacterial cell death.”

“With rapid, bactericidal, broad-spectrum activity including against multidrug resistant pathogens, low rates of resistance, and a favorable safety profile, PLG0206 exemplifies the potential of purposefully designed peptide therapeutics that target the biofilm and the persistent pathogens that make prosthetic joint infection so difficult to treat.”

Importantly, according to Dr. Huang, data from the study indicated that an increase in administered dose of PLF0206 was linearly related to drug exposure within the body. “It’s important for us to predict drug exposure levels based on dose to manage and balance pharmacological effect and toxicity ahead of entering in-patient studies.”

“The next steps are to study PLG0206 in our target population which are patients undergoing debridement, antibiotics, and implant retention for treatment of a periprosthetic joint infection occurring after total knee arthroplasty.”

“This is an indication which has a significant unmet medical need. The outcomes of patients with periprosthetic joint infections are poor, with very few treatment options. Current available systemic and oral antibiotics are often ineffective because of poor biofilm penetration. Despite available antibiotics, there is a 60% failure rate and a five-year mortality of approximately 25%.”

“Because of PLG0206’s favorable profile and the urgent unmet medical need in this area, our next step is to initiate a Phase 1b trial in the U.S. to initiate a study PLG0206 in patients who develop a periprosthetic joint infection of the knee in the first quarter of 2022.”

PLG0206 was invented by Peptilogics CEO Dr. Jonathan Steckbeck based on the hypothesis that anti-infective compounds were an ideal starting point to explore and test his theories about peptide drug design while also treating serious and life-threatening diseases. Importantly, his company developed an artificial intelligence-based discovery platform to study the entire range of peptide based compounds and therapeutics and to do it, of course, at scale.