Trellis Bioscience's TRL1068 Study Published in AAC: A Breakthrough in AMR
Trellis Bioscience Inc
4 min read
REDWOOD CITY, CA / ACCESSWIRE / July 16, 2024 / Trellis Bioscience, Inc. is excited to announce the peer-reviewed publication of the results of a landmark clinical study in a leading infectious disease journal, Antimicrobial Agents and Chemotherapy (AAC), from the American Society of Microbiology on July 16, 2024. The study highlights significant advancements in treating biofilm-associated infections using TRL1068, a human monoclonal antibody that disrupts bacterial biofilm. The results highlight the potential impact of this innovative agent in combating antimicrobial resistance (AMR).
The article, entitled "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" shows that TRL1068 is well tolerated, with favorable biodistribution. In addition, the study showed substantial reductions in biofilm in treated patients, including the complete elimination from the infected prostheses of three patients. Biofilms, complex and naturally occurring communities of bacteria protected by an extracellular matrix, are a major obstacle in treating drug-resistant bacterial infections. Conventional antibiotics typically fail against biofilm-embedded bacteria due to reduced access and altered bacterial physiology.
TRL1068 is a monoclonal antibody targeting the DNABII protein family that is important for biofilm stability. The study showed that it effectively disrupted biofilm in chronic prosthetic joint infection (PJI). Consistent with previously published data in animal models, this disruption facilitated the efficacy of antibiotics against diverse bacterial pathogens, leading to a substantial reduction in infection recurrence compared to control patients.
TRL1068's high efficacy across a wide spectrum of bacterial pathogens included polymicrobial infections. By altering the biofilm environment, TRL1068 enables antibiotics to regain effectiveness against previously resistant bacteria. This approach holds promise for enhancing treatment outcomes well beyond chronic PJI. The study also confirmed TRL1068's excellent safety profile. No significant adverse events were attributed to the treatment, indicating that it is well tolerated for therapeutic use.
TRL1068's mechanism targets a wide range of bacterial species, including all of the priority pathogens identified by the World Health Organization (WHO). These findings pave the way for further clinical development of TRL1068, potentially transforming the management of biofilm-related infections across multiple indications.
Stefan Ryser, PhD., CEO at Trellis Bioscience, commented, "We can no longer ignore that biofilm plays an important role in antimicrobial resistance (AMR) and that disrupting biofilm is a useful strategy to overcome this threat. Historically, all commercially available antibiotics were discovered using planktonic (freely growing) bacteria without regard to their efficacy against bacteria within the biofilm, their natural state of growth. This systematic discovery bias has resulted in significant limitations on the clinical utility of current antibiotics. TRL1068 renders bacteria planktonic, making conventional antibiotics work again."
These clinical study results mark a significant advancement in combating AMR. Trellis CEO also said, "AMR cannot be resolved with one new magic antibiotic. However, this single new mechanism of action has the potential to make a broad range of antibiotics effective against AMR."
Trellis CEO further elaborated, "We have an agreement with the FDA on the design of a Phase 2 study whose goal is to eliminate the need for a 2-stage surgery, the standard of care in PJI. We are also exploring other indications, such as bloodstream infections and bronchial infections, for which published work has shown that biofilm is present in both acute and chronic infections."
About Trellis Bioscience:
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
About Clinical TRL1068: 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.
Contact Information
Company: Trellis Bioscience Inc Address: 702 Marshall Street, Suite 301, Redwood City, CA 94063 Email: info@trellisbio.com Website: trellisbio.com
