Safety and Anti-Inflammatory Effects of Engineered Extracellular Vesicles (ILB-202) for NF-κB Inhibition: A...

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• Dysregulated nuclear factor-kappa B (NF-κB) signaling drives inflammatory and autoimmune diseases.
• Current NF-κB inhibitors risk broad immunosuppression.
• Extracellular vesicles (EVs) offer a safer alternative for therapeutic delivery.

Purpose of the Study:

• To evaluate the safety, tolerability, and preliminary pharmacodynamic effects of ILB-202, an engineered EV loaded with super-repressor IκBα.
• To assess ILB-202's potential immunomodulatory activity in a phase 1 clinical trial.

Main Methods:

• A single-center, randomized, double-blind, placebo-controlled phase 1 trial.
• Administered single ascending intravenous doses of ILB-202 to 18 healthy volunteers.
• Assessed safety, tolerability, and pharmacodynamics using laboratory tests, vital signs, cytokine profiling, and single-cell RNA sequencing.

Main Results:

• ILB-202 was well-tolerated across all doses with no serious adverse events.
• Observed minor adverse events included transient NK cell reduction and mild neutropenia.
• Single-cell RNA sequencing indicated a shift towards an anti-inflammatory state, with modulated NF-κB, enhanced TGF-β and visfatin, and reduced TNF signaling.

Conclusions:

• ILB-202 demonstrates a favorable safety profile and potential immunomodulatory effects.
• These findings support further investigation of ILB-202 for diseases involving aberrant NF-κB activation.