- Clinical proof-of-concept has been achieved for TRL1068 in a planned interim analysis based on completion of the second of three escalating dose groups
- 75% of chronic PJI patients treated with a single dose of TRL1068 and standard antibiotics had a bacterial biofilm burden below 100 CFU/mL sonication fluid after only 7 days of treatment. Although the sample size is small (n=8), this finding compares very favorably to historical data where only 15% of PJI patients are below that mark
- Remarkably, in a quarter of the TRL1068-treated patients, biofilm was removed below the limit of detection after only 7 days of treatment
- TRL1068 is well-tolerated across both dose groups with no drug-related adverse events
REDWOOD CITY, CA, USA I May 4, 2023 I Trellis Bioscience Inc, a clinical stage privately held biotechnology company focused on the discovery and development of native human monoclonal antibodies, today announced a clinical proof-of-concept milestone from a planned interim analysis of the company’s Phase 1 trial of its lead antibody, TRL1068 (calpurbatug), in patients with prosthetic joint infections (PJI). TRL1068 has the potential to disrupt bacterial biofilm and thereby enable difficult-to-treat bacterial infections to be treated with standard antibiotics.
Six of 8 PJI patients (75%) treated with a single dose of TRL1068 and standard antibiotics had a bacterial biofilm burden below 100 CFU/mL sonication fluid after only 7 days of treatment. This compares very favorably to historical data where only 15% of PJI patients are below 100 CFU/mL sonication fluid. Remarkably, in two of the TRL1068-treated patients, biofilm was removed below the limit of detection. As these are novel findings, Trellis Bioscience is the first company to define the 100 CFU/mL mark to differentiate between high and low bacterial biofilm load on surgically extracted prostheses, and to use historical data of sonication fluid CFU counts as an efficacy measure in PJI.
Positive safety and clear trends of efficacy were demonstrated in the first 11 patients randomized across two of three escalating dose groups.
“Although the number of TRL1068-treated PJI patients to date is small and the study was not intended to achieve statistical significance for efficacy, the total removal of bacterial biofilm burden in two patients and the trend toward lower biofilm burden in other treated patients after only 7 days of treatment as compared to robust historical data, are very encouraging. Long experience has established that antibiotics alone cannot remove the biofilm burden. At study entry we confirmed the presence of an infection for each subject by growing a culture of a needle aspirate of the joint synovial fluid, a very robust test,” said Stefan Ryser, Ph.D, Trellis CEO.
These remarkable outcomes provide a foundation for the design of a Phase 2 study aimed at demonstrating that treatment with TRL1068 over a longer time period, in conjunction with standard antibiotic care, can eliminate the infection and thus preserve the original prosthetic joint in patients with PJI. This has the potential to replace the current standard of care, a highly burdensome 2-stage surgical replacement process, with a non-surgical intervention.
TRL1068 was well tolerated across both dose groups (6mg/kg and 15mg/kg). No drug-related adverse events were reported, and no dose-limiting toxicities were identified. Enrollment into the third and last dose cohort (30 mg/kg) is in progress.
“We are excited about these unexpected positive results. As a physician I would have never thought we would observe eradication of biofilm-embedded bacterial pathogens after only 7 days of treatment in a bacterial biofilm that may have grown over a period of years. Based on our currently available preclinical and clinical data we have the expectation of successfully treating, without the need for surgery, chronic prosthetic joint infections and other infections of implanted medical devices and opening a pathway for the treatment of diabetic foot, pulmonary and many other difficult to eradicate biofilm-associated infections,” said Anton Leighton, M.D., Trellis CMO.
“I want to thank the patients and their families, the treating physicians and clinical staff, our employees and consultants, and our funders for bringing us to this exciting milestone and for their continued efforts on the study. We are looking forward to completing the ongoing Phase 1 study and continuing clinical development with a novel Phase 2 study design, where we will evaluate the capacity of TRL1068 to spare patients from surgery. Once we can eliminate the biofilm “shield”, wherein bacteria are highly resistant to antibiotic treatment, standard antibiotics will become substantially more effective in eliminating this difficult-to-treat disease without the need for surgery,” said Trellis CEO, Stefan Ryser, Ph.D.
“A further advantage of TRL1068 is that we expect this native human antibody can be administered multiple times without causing neutralizing antibodies. Due to its phenomenal broad-spectrum activity, we should be able to not only treat staphylococcus infections, but the entire gamut of bacterial infections, including enterobacter, enterococcus, streptococcus, propionibacterium, pseudomonas and others that plague PJI patients,” said Trellis CSO and founder Larry Kauvar, Ph.D.
About Prosthetic Joint Infections
The treatment of bacterial infection of implanted medical devices represents a growing unmet need due to the rapidly increasing number of such implants, with over 1 million hip and knee replacements performed each year in the U.S. alone. While these procedures may improve mobility and quality of life, they are associated with complications, including chronic prosthetic joint infections (PJI). Pathogenic bacteria associated with PJI often form biofilms on the prosthesis, thereby shielding the bacteria from eradication by antibiotics, resulting in PJI becoming a difficult-to-treat disease. As biofilm cannot be removed by antibiotics, the current standard treatment of chronic PJI is a two-stage surgical procedure consisting of removal of the infected prosthesis, implant of an antibiotic eluting spacer for several months, and an additional extensive surgical operation to remove the spacer and implant a new prosthesis. This costly and invasive two-stage process substantially and adversely affects quality of life, with increased immobility and morbidity in addition to decreased 5-year survival rates in patients with PJI when compared with noninfected patients that receive a joint replacement.
About Clinical Study TRL1068-101
Trellis’ clinical study TRL1068-101 is a first-in-human Phase 1, double-blinded, randomized, placebo-controlled single ascending dose study designed to evaluate safety, pharmacokinetics and activity of TRL1068 in subjects with PJI of the knee or hip (ClinicalTrials.gov Identifier: NCT04763759). Subjects are treated with a single infusion of TRL1068 in conjunction with standard antibiotic care for 7 days, prior to receiving primary two-stage exchange arthroplasty, a surgical procedure which is the current standard of care for the treatment of chronic PJI. The study aims to randomize 18 patients across three dose groups. Although designed primarily as a safety clinical trial, the study in infected patients provides an opportunity to gain insight into efficacy.
About Trellis Bioscience Inc.
Trellis Bioscience is a clinical stage privately held company focused on discovering and developing native human monoclonal antibodies for the treatment and prevention of 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 has reduced likelihood of toxicity arising from off-target reactivity and increased likelihood of efficacy arising from the selection of elite antibodies from donors who have successfully overcome the disease.
SOURCE: Trellis Bioscience
Post Views: 487
- Clinical proof-of-concept has been achieved for TRL1068 in a planned interim analysis based on completion of the second of three escalating dose groups
- 75% of chronic PJI patients treated with a single dose of TRL1068 and standard antibiotics had a bacterial biofilm burden below 100 CFU/mL sonication fluid after only 7 days of treatment. Although the sample size is small (n=8), this finding compares very favorably to historical data where only 15% of PJI patients are below that mark
- Remarkably, in a quarter of the TRL1068-treated patients, biofilm was removed below the limit of detection after only 7 days of treatment
- TRL1068 is well-tolerated across both dose groups with no drug-related adverse events
REDWOOD CITY, CA, USA I May 4, 2023 I Trellis Bioscience Inc, a clinical stage privately held biotechnology company focused on the discovery and development of native human monoclonal antibodies, today announced a clinical proof-of-concept milestone from a planned interim analysis of the company’s Phase 1 trial of its lead antibody, TRL1068 (calpurbatug), in patients with prosthetic joint infections (PJI). TRL1068 has the potential to disrupt bacterial biofilm and thereby enable difficult-to-treat bacterial infections to be treated with standard antibiotics.
Six of 8 PJI patients (75%) treated with a single dose of TRL1068 and standard antibiotics had a bacterial biofilm burden below 100 CFU/mL sonication fluid after only 7 days of treatment. This compares very favorably to historical data where only 15% of PJI patients are below 100 CFU/mL sonication fluid. Remarkably, in two of the TRL1068-treated patients, biofilm was removed below the limit of detection. As these are novel findings, Trellis Bioscience is the first company to define the 100 CFU/mL mark to differentiate between high and low bacterial biofilm load on surgically extracted prostheses, and to use historical data of sonication fluid CFU counts as an efficacy measure in PJI.
Positive safety and clear trends of efficacy were demonstrated in the first 11 patients randomized across two of three escalating dose groups.
“Although the number of TRL1068-treated PJI patients to date is small and the study was not intended to achieve statistical significance for efficacy, the total removal of bacterial biofilm burden in two patients and the trend toward lower biofilm burden in other treated patients after only 7 days of treatment as compared to robust historical data, are very encouraging. Long experience has established that antibiotics alone cannot remove the biofilm burden. At study entry we confirmed the presence of an infection for each subject by growing a culture of a needle aspirate of the joint synovial fluid, a very robust test,” said Stefan Ryser, Ph.D, Trellis CEO.
These remarkable outcomes provide a foundation for the design of a Phase 2 study aimed at demonstrating that treatment with TRL1068 over a longer time period, in conjunction with standard antibiotic care, can eliminate the infection and thus preserve the original prosthetic joint in patients with PJI. This has the potential to replace the current standard of care, a highly burdensome 2-stage surgical replacement process, with a non-surgical intervention.
TRL1068 was well tolerated across both dose groups (6mg/kg and 15mg/kg). No drug-related adverse events were reported, and no dose-limiting toxicities were identified. Enrollment into the third and last dose cohort (30 mg/kg) is in progress.
“We are excited about these unexpected positive results. As a physician I would have never thought we would observe eradication of biofilm-embedded bacterial pathogens after only 7 days of treatment in a bacterial biofilm that may have grown over a period of years. Based on our currently available preclinical and clinical data we have the expectation of successfully treating, without the need for surgery, chronic prosthetic joint infections and other infections of implanted medical devices and opening a pathway for the treatment of diabetic foot, pulmonary and many other difficult to eradicate biofilm-associated infections,” said Anton Leighton, M.D., Trellis CMO.
“I want to thank the patients and their families, the treating physicians and clinical staff, our employees and consultants, and our funders for bringing us to this exciting milestone and for their continued efforts on the study. We are looking forward to completing the ongoing Phase 1 study and continuing clinical development with a novel Phase 2 study design, where we will evaluate the capacity of TRL1068 to spare patients from surgery. Once we can eliminate the biofilm “shield”, wherein bacteria are highly resistant to antibiotic treatment, standard antibiotics will become substantially more effective in eliminating this difficult-to-treat disease without the need for surgery,” said Trellis CEO, Stefan Ryser, Ph.D.
“A further advantage of TRL1068 is that we expect this native human antibody can be administered multiple times without causing neutralizing antibodies. Due to its phenomenal broad-spectrum activity, we should be able to not only treat staphylococcus infections, but the entire gamut of bacterial infections, including enterobacter, enterococcus, streptococcus, propionibacterium, pseudomonas and others that plague PJI patients,” said Trellis CSO and founder Larry Kauvar, Ph.D.
About Prosthetic Joint Infections
The treatment of bacterial infection of implanted medical devices represents a growing unmet need due to the rapidly increasing number of such implants, with over 1 million hip and knee replacements performed each year in the U.S. alone. While these procedures may improve mobility and quality of life, they are associated with complications, including chronic prosthetic joint infections (PJI). Pathogenic bacteria associated with PJI often form biofilms on the prosthesis, thereby shielding the bacteria from eradication by antibiotics, resulting in PJI becoming a difficult-to-treat disease. As biofilm cannot be removed by antibiotics, the current standard treatment of chronic PJI is a two-stage surgical procedure consisting of removal of the infected prosthesis, implant of an antibiotic eluting spacer for several months, and an additional extensive surgical operation to remove the spacer and implant a new prosthesis. This costly and invasive two-stage process substantially and adversely affects quality of life, with increased immobility and morbidity in addition to decreased 5-year survival rates in patients with PJI when compared with noninfected patients that receive a joint replacement.
About Clinical Study TRL1068-101
Trellis’ clinical study TRL1068-101 is a first-in-human Phase 1, double-blinded, randomized, placebo-controlled single ascending dose study designed to evaluate safety, pharmacokinetics and activity of TRL1068 in subjects with PJI of the knee or hip (ClinicalTrials.gov Identifier: NCT04763759). Subjects are treated with a single infusion of TRL1068 in conjunction with standard antibiotic care for 7 days, prior to receiving primary two-stage exchange arthroplasty, a surgical procedure which is the current standard of care for the treatment of chronic PJI. The study aims to randomize 18 patients across three dose groups. Although designed primarily as a safety clinical trial, the study in infected patients provides an opportunity to gain insight into efficacy.
About Trellis Bioscience Inc.
Trellis Bioscience is a clinical stage privately held company focused on discovering and developing native human monoclonal antibodies for the treatment and prevention of 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 has reduced likelihood of toxicity arising from off-target reactivity and increased likelihood of efficacy arising from the selection of elite antibodies from donors who have successfully overcome the disease.
SOURCE: Trellis Bioscience
Post Views: 487
