TRL1068 / Trellis Biosci - LARVOL DELTA

Antibiotics and non-traditional antimicrobial agents for carbapenem-resistant Acinetobacter baumannii in Phase 1, 2, and 3 clinical trials. (PubMed, Expert Opin Investig Drugs) - "Specifically, 9 antibiotics are in Phase 1 (R-327, xeruborbactam/QPX-7728, upleganan/SPR-206, MRX-8, QPX-9003, zifanocycline/KBP-7072, apramycin/EBL-1003, zosurabalpin/RG-6006, and ANT-3310), two in Phase 2 (BV-100, OMN-6), and two in Phase 3 (zidebactam/WCK-5222, funobactam/XNW-4107) clinical trials...In particular, two monoclonal antibodies (TRL-1068, CMTX-101), a phage therapy (Phagebank), an immune-modulating agent (recombinant human plasma gelsolin/Rhu-pGSN), a microbiome-modulating agent (SER-155), and an engineered cationic antibiotic peptide (PLG-0206). Several agents with promising characteristics against CRAB infections are in clinical development (Phases 1, 2, and 3). The urgent need for therapeutic options against CRAB infections necessitates optimizing efforts and time for introducing successfully studied agents into clinical practice."

Journal • Review • Infectious Disease • GSN

Antibiotics and non-traditional antimicrobial agents for pseudomonas aeruginosa in clinical phases 1, 2, and 3 trials. (PubMed, Expert Opin Investig Drugs) - "Traditional agents in clinical development include β-lactam/β-lactamase inhibitors (funobactam, taniborbactam, QPX2014-xeruborbactam), aminoglycosides (apramycin), polymyxin derivatives (upleganan, MRX-8, and SPR741), fluoroquinolones (MP-376), and lipopolysaccharide transport inhibitors (murepavadin). Non-traditional antibiotics in clinical development include anti-virulence agents (fluorothiazinone), monoclonal antibodies (INFEX-702, TRL-1068, and CMTX-101), bacteriophages (AP-PA02, YPT-01, BX004-A, and WRAIR-PAM-CF1), and miscellaneous agents (AR-501, PLG-0206, SNSP-113, OligoG CF-5/20, and ALX-009). A considerable number of antimicrobial agents, some with novel mechanisms of action, are in clinical phases of development for treating Pseudomonas aeruginosa infections. The urgent need for more therapeutic options necessitates the rapid optimization of progress to introduce new agents into clinical practice."

Journal • Review • Infectious Disease

Novel Technologies in Periprosthetic Joint Infections: Emerging Therapeutics. (PubMed, J Arthroplasty) - "Anti-DNA-binding class II human monoclonal antibodies (TRL1068) target bacterial biofilm structures, enhancing antibiotic penetration and immune clearance...Future research should focus on validating their efficacy and safety through large-scale clinical trials and integrating them into existing treatment protocols. By leveraging these advances, the orthopaedic community may markedly enhance infection management strategies, reduce treatment failures, and improve patient outcomes in arthroplasty."

Journal • Review • Infectious Disease • Orthopedics • Targeted Protein Degradation

TRL1068-201: Study to Evaluate the Efficacy and Safety of TRL1068 for the Treatment of Prosthetic Joint Infection (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Trellis Bioscience LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Orthopedics

TRL1068-201: Study to Evaluate the Efficacy and Safety of TRL1068 for the Treatment of Prosthetic Joint Infection (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Trellis Bioscience LLC | Trial completion date: Mar 2027 ➔ Nov 2026 | Trial primary completion date: Mar 2027 ➔ Nov 2026

Trial completion date • Trial primary completion date • Infectious Disease • Orthopedics

Study to Evaluate the Efficacy and Safety of TRL1068 for the Treatment of Prosthetic Joint Infection (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Trellis Bioscience LLC

New P2 trial • Infectious Disease • Orthopedics

Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip. (PubMed, Antimicrob Agents Chemother) - P1 | "None of the patients who received TRL1068 had a relapse of the original infection by the end of the study (day 169). This study is registered with ClinicalTrials.gov as NCT04763759."

Journal • P1 data • PK/PD data • Infectious Disease • Orthopedics

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: Trellis Bioscience LLC | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Orthopedics • IL10 • IL6

Human Monoclonal Antibody TRL1068 Disrupts Bacterial Biofilm for Nonsurgical Treatment of Orthopaedic Infections (AAOS 2024) - "Preclinical study results and preliminary data of the ongoing Phase 1 study warrant design of a Phase 2 study in chronic PJI."

Infectious Disease • Orthopedics

Human Monoclonal Antibody TRL1068 Disrupts Bacterial Biofilm for Nonsurgical Treatment of Orthopaedic Infections (AAOS 2024) - "The combination of extensive preclinical study results and the preliminary data of the ongoing Phase 1 study warrant design of Phase 2 studies in which repeat dosing with TRL1068 (an initial dose of 15 mg/kg and 3 maintenance doses of 7.5 mg/kg every 3 weeks) is combined with targeted antibiotic therapy instead of any surgical intervention. Because TRL1068 is a fully human monoclonal antibody, repeated systemic dosing is expected to be well tolerated. In addition to PJI, this novel approach has promise for treatment of infected spinal implants and as a prophylaxis for high risk patients such as external fixations of complex fractures."

Infectious Disease • Musculoskeletal Diseases • Orthopedics

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Trellis Bioscience LLC

Trial completion date • Trial primary completion date • Infectious Disease • Orthopedics • IL10 • IL6

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Trellis Bioscience LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Orthopedics • IL10 • IL6

Monoclonal Antibody Disrupts Biofilm Structure and Restores Antibiotic Susceptibility in an Orthopedic Implant Infection Model. (PubMed, Antibiotics (Basel)) - "Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection."

Journal • Infectious Disease • Orthopedics

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Trellis Bioscience LLC | Trial completion date: Sep 2023 ➔ Feb 2024 | Trial primary completion date: Apr 2023 ➔ Nov 2023

Trial completion date • Trial primary completion date • Infectious Disease • Orthopedics • IL10 • IL6

Study to Evaluate Safety and Activity of TRL1068 in Chronic Rhinosinusitis (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Trellis Bioscience LLC | Trial completion date: Jan 2024 ➔ Jan 2025 | Initiation date: Jan 2023 ➔ Jan 2024 | Trial primary completion date: Jan 2024 ➔ Jan 2025

Trial completion date • Trial initiation date • Trial primary completion date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Trellis Bioscience LLC | N=28 ➔ 18 | Trial completion date: Mar 2023 ➔ Aug 2023 | Trial primary completion date: Dec 2022 ➔ Mar 2023

Enrollment change • Trial completion date • Trial primary completion date • Infectious Disease • Orthopedics • IL10 • IL6

Study to Evaluate Safety and Activity of TRL1068 in Chronic Rhinosinusitis (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Trellis Bioscience LLC | Initiation date: Sep 2022 ➔ Jan 2023

Trial initiation date • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Study to Evaluate Safety and Activity of TRL1068 in Chronic Rhinosinusitis (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Trellis Bioscience LLC

New P1 trial • Chronic Rhinosinusitis With Nasal Polyps • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

Study to Evaluate Safety and Activity of TRL1068 in Prosthetic Joint Infections (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Trellis Bioscience LLC | Trial completion date: Jul 2022 ➔ Mar 2023 | Trial primary completion date: Feb 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Infectious Disease • Orthopedics • IL10 • IL6