https://lnkd.in/db6a9nHp Significance of Biofilm Disruption — Trellis Bioscience's TRL1068: Advancing a New Class of Anti-Infective Drugs David Thompson Aug 04, 2024 In the natural world, biofilm is a complex aggregate of bacteria and a bacterially produced extracellular matrix that provides a protective environment for the microorganisms, shielding them from natural antibiotics and acute environmental stressors such as nutrient restriction, desiccation, UV radiation, extreme temperature, and pressure, and high alkalinity or acidity. Biofilms affect industrial pipes and underwater structures and are ubiquitous in soil [1]. In the human body, bacteria in biofilms are protected from attack by pharmaceutical antibiotics and by the immune system, allowing persistence even in hostile conditions. Within the biofilm matrix, bacterial cells adopt a defensive physiological state that includes coordinated expression of multiple resistance genes [2]. Trellis Bioscience's TRL1068 is the first clinical-stage agent for a new class of drugs called biofilm disruptors [6]. Clinical proof-of-concept for TRL1068 was achieved in patients with periprosthetic joint infections (PJI) [7]. Lower extremity (knee and hip) total joint arthroplasties are among the most commonly performed surgical procedures in the USA, providing a substantially improved quality of life for most patients. However, despite advances in perioperative antiseptic protocols, surgical technique, and operating room sterility, infection remains the most common cause of prosthetic joint failure within the first year after primary arthroplasty [8], affecting ~2% of patients.
Trellis Bioscience Inc.
Biotechnology Research
Redwood City, California 457 followers
Our human mAb TRL1068 disrupts bacterial biofilm and makes traditional antibiotics work again overcoming drug resistance
About us
Trellis Bioscience is a clinical-stage company focused on discovering and developing native human monoclonal antibodies to treat and prevent drug-resistant, life-threatening infectious diseases. Antibodies are the immune system's most potent natural weapon against disease. Trellis's innovative proprietary technology CellSpot™ overcomes technical obstacles that have long hindered exploiting the full human antibody repertoire. This ideal source of drugs focuses on the selection of elite antibodies that bind highly conserved target epitopes with high affinity. TRL1068 is a native human monoclonal antibody (for intravenous delivery) whose target is a family of bacterial proteins (DNABII) that play a critical role in maintaining the structural integrity of biofilms by anchoring extracellular bacterial DNA (eDNA) from dead bacteria within the biofilm matrix. TRL1068 binds at high affinity (Kd ~50 pM) to a highly conserved epitope found in nearly all medically significant bacteria, including both Gram-positive and Gram-negative species. High affinity binding to DNABII ensures that the protein is eliminated from the body and thus prevents its deposition elsewhere in the body, where it could form biofilm metastases. Because the bacterial target is only exposed to the antibody after the producing bacterial cell is dead, resistance to this novel intervention is expected to be rare. The FDA granted Fast Track, QIDP (qualified infectious disease product), and Orphan Drug designations for TRL1068.
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Trellis Bioscience Inc. reposted this
Clinical proof-of-concept in a landmark trial in AMR to disrupt biofilm in patients with chronic periprosthetic joint infections.
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 | Antimicrobial Agents and Chemotherapy
journals.asm.org
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Clinical proof-of-concept in a landmark trial in AMR to disrupt biofilm in patients with chronic periprosthetic joint infections.
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 | Antimicrobial Agents and Chemotherapy
journals.asm.org