Pittsburgh-based CytoAgents Inc. has announced the successful completion of the first dose cohort in its Phase 1b/2a clinical trial evaluating CTO1681 for the prevention and treatment of Cytokine Release Syndrome (CRS). Following a comprehensive review of safety and efficacy data, the Safety Review Committee (SRC) has approved dose escalation to the next higher planned dose level in Cohort 2.
The initial cohort included patients with Diffuse Large B-Cell Lymphoma (DLBCL) receiving CAR T-Cell Therapy who were at risk for developing CRS. Data from this cohort demonstrated a favorable safety profile, with no dose-limiting toxicities (DLTs) or drug-related serious adverse events (SAEs) observed. Importantly, researchers noted no interference with the CAR T-Cell Therapy itself.
"This milestone marks an important step forward in our mission to deliver a safe, effective therapy for Cytokine Release Syndrome," said Teresa Whalen, RPh, CEO of CytoAgents. "We remain focused on advancing through the next stages of this trial and ultimately delivering a much-needed treatment option for patients facing this life-threatening immune response."
Trial Design and Objectives
The ongoing trial (NCT05905328) is designed as an open-label, dose-escalation, multi-center study evaluating the safety, tolerability, and preliminary efficacy of CTO1681. The study follows a standard rolling six dose-escalation design, with primary objectives of assessing the safety profile and pharmacokinetics of CTO1681, while determining the Recommended Phase 2 Dose (RP2D).
Arthur P. Bertolino, MD, PhD, MBA, Chief Medical Officer of CytoAgents, expressed optimism about the initial findings: "The safety and early efficacy data from the first dose cohort are encouraging. We look forward to evaluating the higher dose cohorts to further study the potential of CTO1681 to prevent and treat CRS, a very significant toxicity of CAR T-Cell Therapy."
Addressing a Critical Unmet Need
Cytokine Release Syndrome represents a significant challenge in cancer immunotherapy, particularly for patients receiving CAR T-Cell Therapy. This potentially life-threatening condition occurs when the immune system overreacts, releasing excessive inflammatory cytokines that can lead to systemic inflammation, organ damage, and in severe cases, death.
The majority of patients undergoing CAR T-Cell Therapy for cancer experience CRS and associated neurotoxicity, highlighting the substantial unmet medical need for effective preventive and treatment options. Current management approaches for CRS are limited and often involve immunosuppressive agents that may compromise the efficacy of the primary cancer therapy.
Novel Mechanism of Action
CTO1681 employs an innovative approach to addressing CRS. Unlike conventional immunosuppressive strategies, this investigational drug uses a host-directed approach that targets the underlying mechanisms of CRS by modulating the body's natural immune response to sickness or disease.
This mechanism potentially offers advantages over existing approaches by specifically targeting the pathways involved in cytokine dysregulation without broadly suppressing immune function, which could preserve the anti-cancer activity of CAR T-Cell Therapy while mitigating its inflammatory side effects.
Broader Applications
While the current trial focuses on CRS in the context of CAR T-Cell Therapy for DLBCL, CytoAgents envisions broader applications for CTO1681. According to company information, they aim to develop treatments for multiple indications with high unmet need, including CRS triggered by bispecific antibody therapies, respiratory epidemics, and autoimmune illnesses.
The company's approach reflects the growing recognition that managing immune-related adverse events is crucial for improving outcomes across various therapeutic modalities, particularly as advanced immunotherapies become more widely used in clinical practice.
About CytoAgents
CytoAgents Inc. is a privately held, clinical-stage biotechnology company focused on developing innovative pharmaceutical products for treating life-threatening symptoms associated with Cytokine Release Syndrome. The company's lead compound, CTO1681, targets the underlying cause of life-threatening CRS through its novel mechanism of action.
Based in Pittsburgh, CytoAgents is committed to developing first-in-class, best-in-class products that address major medical needs in the management of inflammatory conditions resulting from therapeutic interventions and disease processes.
As the trial progresses to higher dose cohorts, the medical and scientific communities will be watching closely to see if CTO1681 can fulfill its promise of providing a safer approach to managing one of the most challenging complications of modern cancer immunotherapy.
