FDA Grants Orphan Drug Designation for Prosthetic Joint Infections Treatment

Peptilogics has announced that the US Food and Drug Administration (FDA) has granted Orphan Drug Designation for PLG0206, the company's first-in-class, broad-spectrum antibiotic peptide, for the treatment of prosthetic joint infections (PJI), a rare life-threatening condition that may result from arthroplasty or joint replacement procedures.

"PLG0206 is the first novel anti-infective to be granted Orphan Drug Designation, confirmation that we are advancing a meaningful therapy that can address an unmet medical need, beginning with PJI," said Jonathan Steckbeck, PhD, Founder and CEO of Peptilogics. "This advance, combined with recent enhancements to our discovery platform, are enabling faster development of novel peptide therapies against any targets of interest, putting Peptilogics in a unique position to respond to the evolving landscape of infectious pathogens as well as other diseases worldwide."

"This is a great accomplishment for Peptilogics and for the orthopedic community," said Javad Parvizi, MD, James Edwards Professor of Orthopaedic Surgery, Sidney Kimmel School of Medicine, Rothman Institute at Thomas Jefferson University. "Orthopedic infections cause an immense psychological and financial burden on our patients. Many endure multiple operations, receive long-term antimicrobial treatment with significant adverse events, and at the conclusion of this long and tumultuous journey, joint failure still occurs. Patients are desperate for a novel treatment strategy for PJI, and we are excited that PLG0206 is on track to be the first treatment to fill that clinical void."

The Orphan Drug Designation program grants orphan status to drugs intended for the treatment of a rare disease that affects fewer than 200,000 people in the US. Programs with Orphan Drug status may receive partial tax credit for clinical trial expenditures, waived user fees and eligibility for seven years of marketing exclusivity. The granting of an orphan designation request does not alter the standard regulatory requirements for obtaining marketing approval.

"Peptilogics' technology is moving closer to approval for its first indication, serving a significant unmet need," said Jason Camm, Managing Director and Chief Medical Officer of Thiel Capital and Peptilogics Board Director. "This marks a promising regulatory milestone for Peptilogics' lead program, and I'm equally as excited to see Peptilogics continue to expand its computational discovery platform to advance their approach to rapid peptide drug discovery."

More than 1 million total joint replacements are performed annually in the U.S., a number that is expected to grow to 4 million annual procedures by 2030 due to an aging and growing population. Following joint replacement, patients who develop a PJI face a serious life-threatening condition with few to no effective treatment options available and often require major surgery in an attempt to resolve the infection. These additional follow-on surgical procedures result in substantial numbers of patient deaths, evidenced by a 20% 5-year mortality rate, higher than that found in either breast or prostate cancers.

This current treatment standard has a high failure rate predominantly due to the presence of biofilm bacteria which makes the eradication of the infecting pathogen extremely difficult. Biofilms are a matrix composed of polysaccharides, extracellular DNA, proteins, and lipids that allow certain bacteria known as "persister" pathogens to avoid standard antibiotics. Unfortunately, the most common bacteria in PJI is a prolific biofilm producer.

Peptilogics discovered a new class of anti-infectives, using their proprietary algorithmic design process, which have applications across multiple industries and a broad spectrum of resistant bacteria. Their lead candidate, PLG0206, has a novel mechanism of action that works by targeting and disrupting bacterial membranes leading to the death of bacterial cells. PLG0206 has demonstrated best-in-class, broad-spectrum activity against pathogens identified by the WHO and the CDC as critical, urgent, or high priority targets.

PLG0206, unlike standard antibiotics, directly addresses the biofilm and the persister pathogens commonly present in PJI. PLG0206 is an engineered, cationic antibiotic peptide, and is a next generation agent based on the principles found in naturally occurring antimicrobial peptides (AMPs). AMPs serve as a first line of defense against invading pathogens, have activity over a wide variety of pathogens, and exhibit potent activity in eliminating biofilms. Despite AMPs' potential as antibacterials, traditional approaches to discovery have been unable to overcome challenges of toxicity. Unlike other AMPs, PLG0206 was designed to maximize safety while keeping the broad spectrum activity as well as the unique ability to eliminate biofilms.