PIPELINE
Designing and Advancing Peptide Therapeutics with Purpose
Peptilogics is creating novel therapeutics to transform the treatment and prevention of serious medical device-related infections
Drug & Formulation
Treatment/Prevention
Disease Area
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
Treatment: PLG0206 Irrigation
Treatment/Prevention:
Treatment
Disease Area:
Prosthetic Joint Infections
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
Treatment/Prevention:
Treatment
Disease Area:
Fracture/ Trauma Infections*
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
Treatment/Prevention:
Treatment
Disease Area:
Spine Infections*
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
Treatment/Prevention:
Treatment
Disease Area:
Medical Device Infections
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
Prevention: PLG0206 Controlled Release
Treatment/Prevention:
Prevention
Disease Area:
Fracture/ Trauma Infections**
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
Treatment/Prevention:
Prevention
Disease Area:
Medical Device Infections
Preclinical
Phase 1
Phase 1b (POC)
Phase 2/3 (Pivotal)
*Directly into Phase 2 or 3
**Funded by CARB-X
Lead PROGRAM: PLG0206
PLG0206 is a novel engineered cationic antimicrobial peptide (eCAP) based on naturally occurring antimicrobial peptides (AMPs). AMPs are key components of the immune system that provide first-line defense against pathogens and modulate immune responses. Although natural AMPs can possess potent anti-biofilm activity, their clinical use has been limited by systemic toxicity, rapid degradation leading to short in-vivo half-life, and loss of efficacy under bodily conditions. PLG0206 was rationally designed to overcome these limitations, resulting in a novel broad-spectrum, rapid-acting agent, active against planktonic and biofilm-embedded ‘persister’ organisms, including multidrug-resistant pathogens. By acting through direct membrane disruption rather than metabolic inhibition, PLG0206 kills planktonic bacteria within seconds and eliminates biofilm within minutes of exposure, while retaining activity in complex biological fluids. PLG0206 is a novel rapid-acting ‘biofilm buster’ with potential utility across surgical settings. Local intra-articular irrigation delivers high bactericidal concentrations of PLG0206 at the infection site with minimal systemic absorption, providing a mechanistically novel first-line treatment for periprosthetic joint infections (PJI) and other medical device-related infections (MDRIs).
Based on preclinical and clinical studies, Peptilogics has received multiple regulatory designations that support the development pathway for PLG0206, including:
- QIDP (Qualified Infectious Disease Product) designation, which provides 5 additional years of market exclusivity upon approval
- Orphan Drug Designation for the treatment of PJI
- Fast Track Designation to facilitate development and expedite FDA review
Clinical Program:
PLG0206 was first studied for systemic safety in humans as an intravenous (IV) formulation. Subsequent and ongoing trials are being conducted with PLG0206 Irrigation Solution (IRR) for use by orthopedic surgeons to treat PJI.
More information regarding prior and ongoing trials
Phase 1:
PLG0206 Intravenous: In a randomized, placebo-controlled, ascending dose study in healthy volunteers, PLG0206 was safe and well tolerated when administered intravenously at single doses up to 1 mg/kg over 1 to 4 hours (Huang 2022). Following 1 mg/kg PLG0206, the mean Cmax was 2653 ng/mL. PLG0206 exhibited linear pharmacokinetics over the dose range, with a median terminal half-life ranging from 7 to 20 hours.
Phase 1b (POC):
PLG0206 Irrigation Solution was studied in a prospective, open-label, non-randomized, interventional trial conducted in patients across seven US-based orthopedic surgical centers, adult patients with well-fixed prosthesis undergoing DAIR (Debridement, Antibiotics, Implant Retention) for confirmed Total Knee Arthroplasty (TKA) associated Periprosthetic Joint Infection (PJI) were studied. A single intra-articular irrigation with 500 mL PLG0206 solution at 3 or 10 mg/mL was administered by the investigator orthopedic surgeon for 15–18 minutes at the end of a DAIR procedure irrigation, just prior to closure. Patients also received standard systemic antibiotics after surgery. Fourteen patients (9 males, 5 females) were treated, with a median (range) age of 68 (53-78) years and time from index TKA to reported PJI of 78 (4-278) months.
Common comorbidities were cardiac disorders (64.3%), gastrointestinal disorders (64.3%), and diabetes (28.6%); 43% had a body mass index ≥30 kg/m2. PLG0206 was safe and well tolerated. No specific safety signals were identified. Most adverse experiences occurred after Day 5 and were mild/moderate in severity. Systemic exposure was minimal and undetectable by 24 hours. At 12 months, 12/14 patients (85.7%) remained infection-free with prosthesis retained. One patient (7.1%) had PJI recurrence at Day 169 requiring revision surgery. One patient had an indeterminate outcome, being lost to follow-up after Day 21. Investigators concluded that irrigation with PLG0206 during DAIR was safe, well tolerated, and associated with favorable clinical outcomes in this small early-phase study. These data supported further development of PLG0206 as a treatment for PJI and advancement to a pivotal Phase 2b/3 trial.
Phase 2/3 (PIVOTAL):
The RETAIN trial is an ongoing Phase 2b/3 randomized, placebo-controlled study to evaluate the efficacy of PLG0206 in prevention of recurrent infection in patients undergoing debridement, antibiotics, and implant retention (DAIR) for treatment of an active periprosthetic joint infection (PJI) following total knee arthroplasty (TKA), also known as a knee joint replacement. The trial will also assess the safety of PLG0206 when used as an irrigation solution during the DAIR procedure.
Eligible participants will undergo a DAIR procedure according to the treating hospital’s standard of care (SOC). Participant eligibility will be based on clinical and diagnostic assessments, including laboratory results.
Once debridement during DAIR is complete, the Investigator will follow a standardized irrigation protocol, with the final irrigation step being administration of a single dose of blinded study drug (PLG0206 or matching placebo). Following study drug administration, all participants will receive standard post-operative care per institutional guidelines and will be discharged from the hospital in accordance with local standards. Participants may receive IV/oral antimicrobial therapy, as part of post-operative SOC. Participants will be monitored for safety and signs of PJI recurrence or persistent infection for 365 days post study drug administration.
The RETAIN trial is a superiority trial, expected to enroll 240 patients, with the primary endpoint measuring the reduction in clinical failure rates. The study will also evaluate health economics measures including hospitalization duration, readmission rates, and additional surgical procedures to quantify potential cost savings for hospitals, health systems, and payers.
For more information please visit: https://clinicaltrials.gov/study/NCT07214311
*PLG0206 and other product candidates described on this website are investigational and have not been approved by the FDA or any other regulatory authority for commercial use.
What is a Periprosthetic Joint Infection (PJI) and What is the Unmet Need?
Prosthetic Joint Infection (PJI): a growing, under-recognized crisis
Total joint replacement is now the most common major surgical procedure performed worldwide, with volumes accelerating as populations age and obesity, diabetes, and other chronic conditions rise1. While joint replacement outcomes are typically excellent, prosthetic joint infection (PJI) remains the most devastating complication, capable of turning a successful joint replacement into a patient’s and surgeon’s worst nightmare. At any time following surgery—months or even years later—patients can develop a PJI, a serious and potentially life-threatening condition. PJI patients frequently experience severe morbidity, prolonged immobility, loss of independence and productivity, and a five-year mortality rate approaching 25%2, rivaling many cancers. Despite this impact, there are no approved therapeutics in the U.S. specifically indicated for PJI, leaving patients with limited and often unsuccessful treatment options.
Biofilm is the common enemy—and the reason current treatments fail. Hardware-associated infections are uniquely difficult to eradicate because bacteria adhere to implant surfaces and surrounding tissues, forming difficult-to treat-biofilms. These biofilms can block antibiotic penetration and protect dormant bacteria that can persist, despite aggressive therapy. As a result, standard-of-care approaches frequently fail, forcing patients into cycles of repeated surgeries, loss of mobility, hospitalizations, and prolonged antibiotic exposure.
How Often PJI Occurs: PJI occurs in approximately 2.3% and 2.1% of total knee and total hip replacements respectively3, but the risk is two- to three-fold higher (3–5% or more) in patients with high-risk co-morbidities such as obesity, diabetes, renal disease, immune suppression, or prior joint surgery. In the U.S. alone, ~45,000 PJI cases occur each year, and this number is expected to grow substantially as procedure volumes increase. Importantly, PJI is widely underreported in registries and administrative datasets, particularly late-onset and recurrent infections, meaning the true burden is likely significantly higher than reported figures suggest. The problem is accelerating. By 2030, annual volume of knee and hip replacements across the U.S. and Europe is projected to be over 5 million4, each carrying a PJI risk that current medicine cannot reliably prevent or cure. As procedure volumes rise and patient risk profiles worsen, the absolute number of infections—and failures—will continue to climb.
The Burden of PJI: Current treatment pathways demand unacceptable trade-offs. Implant-preserving procedures such as DAIR (debridement, antibiotics, and implant retention) report failure rates of 35-55% in the published literature5. Two-stage revision—the most aggressive surgical option—requires multiple major operations, extended hospitalization, and months of disability, yet still fails 15–25% of the time. The economic impact mirrors the clinical burden: total costs for a single PJI episode often exceed $390,000 per patient, according to data published by Hany Bedair, MD in Clinical Orthopaedics and Related Research.
The implications extend far beyond individual patients. Healthcare systems face mounting pressure from longer hospital stays, repeat surgeries, antibiotic toxicity, and complex care coordination. PJI represents a large, growing, and underserved market—one where effective, biofilm-targeted therapies could fundamentally change outcomes while delivering meaningful value to patients, providers, and payers alike.
*Citations
4SmartTRAK 2025, projection
Resources for Healthcare Professionals
Trial Inquiries
clinicaltrials@peptilogics.com
Clinical Guidelines
Clinical Guidelines & Standards for the Management of Prosthetic Joint Infection
The management of prosthetic joint infection (PJI) is guided by established professional society recommendations developed by orthopedic surgeons and infectious disease experts. Current standards of care draw from the following leading clinical guidelines:
AAOS – Diagnosis and Prevention of Periprosthetic Joint Infections (CPG)
Clinical practice guideline for PJI prevention and diagnosis from the American Academy of Orthopaedic Surgeons.
https://www.aaos.org/globalassets/quality-and-practice-resources/pji/pji-clinical-practice-guideline-final-2-17-21.pdf
American Academy of Orthopaedic Surgeons
MSIS – Musculoskeletal Infection Society (society reference page)
MSIS is the primary authority on PJI diagnostic criteria, definitions, and expert consensus (diagnostic standards widely used in practice and research).
https://pmc.ncbi.nlm.nih.gov/articles/PMC12604139/
These guidelines inform current standards of care; however, treatment outcomes remain suboptimal, highlighting the need for improved, targeted therapeutic approaches.