Trellis Banks on FDA Designations for PJI Antibody as Clinical Evidence Gap Widens Until 2027

Trellis Bioscience Secures $9M Series C for Calpurbatug Phase II PJI Trial

Trellis Bioscience has successfully closed a $9 million Series C funding round, bringing its total equity funding to approximately $35 million. This capital will support the completion of its ongoing Phase II clinical trial for calpurbatug (TRL1068), a monoclonal antibody targeting chronic prosthetic joint infections (PJI). The trial, which is fully enrolled and conducted using a debridement, antibiotics, and implant retention (DAIR) approach, anticipates top-line results in the second quarter of 2027. Calpurbatug has received Orphan Drug, Fast Track, and Qualified Infectious Disease Product designations from the FDA, highlighting its potential in an area with significant unmet medical need.

• Trellis Bioscience's $9 million Series C round was bolstered by continued participation from existing investors New Science Ventures and Easton Capital, alongside new strategic investments from AMR Action Fund (AMRAF), The Doctor Group of Dallas, Texas, and a group of orthopaedic surgeons. This latest infusion brings the company's total equity funding to nearly $35 million, complemented by similar amounts in non-dilutive grants from NIAID and CARB-X, underscoring strong financial backing for its antimicrobial development.
• The funding is specifically earmarked for the completion of the ongoing Phase II clinical trial of calpurbatug (TRL1068), a monoclonal antibody designed to treat chronic prosthetic joint infections. This trial is fully enrolled and follows a debridement, antibiotics, and implant retention (DAIR) approach. Calpurbatug has already demonstrated initial safety and biofilm-disrupting activity in a Phase I trial and has received significant regulatory support from the FDA, including Orphan Drug, Fast Track, and Qualified Infectious Disease Product designations.
• Calpurbatug represents a novel class of agents that disrupt bacterial biofilm, offering a new approach to treating antibiotic-resistant infections, particularly chronic PJI. This condition is a serious complication of joint replacements, currently lacking approved therapeutic options and often requiring challenging two-stage surgeries with high failure rates and increased mortality risk. The drug's mechanism of action and regulatory designations highlight its potential to address a critical unmet medical need in infectious disease.

Addressing the Critical Unmet Needs in Chronic PJI Treatment

Chronic prosthetic joint infections (PJI) remain among the most difficult complications in orthopedic care, driven by biofilm biology, diagnostic uncertainty, and the physical and psychosocial toll of prolonged treatment regimens. Current management strategies—largely reliant on surgical intervention paired with extended antimicrobial therapy—face significant limitations in efficacy, standardization, and patient tolerability. These challenges are further compounded by rising rates of antimicrobial resistance and gaps in joint-specific treatment algorithms.

• Biofilm-mediated resistance and delayed detection: Limited bone vascularization, intracellular bacterial persistence, and dysregulated host immune responses facilitate biofilm formation, which confers resistance to conventional antimicrobials. Delayed diagnosis allows infections to progress into robust, treatment-resistant biofilms, and current diagnostic tests often fail to identify infection at the early stages when intervention is most effective.

• Lack of standardized diagnostic criteria: No universally accepted "gold standard" exists for PJI diagnosis using serum biomarker thresholds. Existing criteria fail to differentiate acute from chronic infections and do not account for time elapsed since the index surgery, complicating consistent clinical decision-making.

• Surgical treatment burden and failure rates: Standard management typically requires two-stage revision surgery combined with rigorous antibiotic therapy, which is physically and psychologically taxing for patients and increases demand for socioeconomic support. Despite optimal care, a subset of patients experience treatment failure, necessitating resection, fusion, or amputation, with some cases requiring multiple revision surgeries.

• Rising antimicrobial resistance: Prolonged antibiotic courses commonly lead to resistance, and outcomes are notably worse in extensively drug-resistant (XDR) versus multidrug-resistant (MDR) cases. Debridement, antibiotics, and implant retention (DAIR) is associated with significantly higher failure rates compared to implant removal, even in early MDR/XDR Gram-negative PJIs (OR = 3.57, 95% CI 1.68–7.58; P < 0.001). Additionally, rifamycin-class agents are prone to rapid resistance development, limiting their use to combination regimens.

• Joint-specific treatment gaps: Management algorithms developed for hip and knee PJI may not be directly applicable to other joints, such as the ankle, where soft tissue quality requires distinct grading considerations. In ankle PJI cases with component retention, cure rates were only 66.7% (14 of 21), with relapses involving both the original and new infecting organisms.

• Complex, individualized decision-making: Optimal management must account for multiple variables—including infection type and duration, pathogen antimicrobial susceptibility, condition of infected tissue and bone stock, patient preferences, and functional status—underscoring the absence of a one-size-fits-all treatment pathway for chronic PJI.

Biofilm-Disrupting Antibody Advances in Chronic PJI

Chronic prosthetic joint infections (PJI) represent a formidable challenge in orthopedic surgery, inflicting substantial morbidity on patients and imposing immense costs on healthcare systems. Despite advancements, current treatment strategies, particularly debridement, antibiotics, and implant retention (DAIR), often yield variable and suboptimal outcomes, especially in chronic cases. This is largely due to the tenacious nature of bacterial biofilms, which shield pathogens from antibiotics and host immune responses, making eradication exceedingly difficult.

The progress of Trellis Bioscience's calpurbatug (TRL1068) into a fully enrolled Phase II trial offers a beacon of hope. As a biofilm-disrupting monoclonal antibody, calpurbatug targets the very mechanism that underpins treatment resistance in PJI. Early Phase I data demonstrated its ability to penetrate synovial fluid and eliminate implant bacteria, suggesting a powerful adjunctive role to DAIR. The FDA's recognition through Orphan Drug, Fast Track, and Qualified Infectious Disease Product designations further underscores the critical unmet need and the potential for an expedited path to market.

However, the journey ahead is not without its complexities. The success of DAIR itself is highly heterogeneous, influenced by factors such as the specific causative organism, the duration of symptoms, and patient-specific comorbidities. For instance, the presence of osteomyelitis in the surrounding bone, a common finding in chronic PJI, significantly lowers success rates. Calpurbatug will need to demonstrate a robust and consistent improvement over these inherent challenges. Furthermore, the landscape of PJI management is continuously evolving, with optimized antibiotic regimens and multidisciplinary care pathways showing improved outcomes. Trellis Bioscience must clearly articulate and prove the additive value of calpurbatug within this dynamic environment. If successful, this novel agent could fundamentally reshape the treatment paradigm for chronic PJI, offering a much-needed solution to a persistent and debilitating condition.