Small-Molecule Neutrophil Modulator ADS051 is Safe and Well-Tolerated in a Phase 1 Single Ascending Dose Study

Area of Science:

• Gastroenterology
• Pharmacology
• Immunology

Background:

• Current ulcerative colitis (UC) treatments have limitations in efficacy and safety.
• Neutrophil transmigration and activation are implicated in UC pathogenesis and symptoms.
• ADS051 is a novel small molecule designed to inhibit neutrophil migration and activation.

Purpose of the Study:

• To evaluate the safety, tolerability, and pharmacokinetics of ADS051 in healthy volunteers.
• To assess ADS051's potential as a therapeutic agent for UC by examining its local action in the gastrointestinal tract.

Main Methods:

• A Phase 1, single ascending dose study involving 50 healthy adults.
• Participants were randomized into 5 cohorts receiving oral doses of ADS051 (100 mg to 3,500 mg) or placebo.
• Safety, tolerability, and pharmacokinetics in stool, blood, and urine were monitored for 30 days post-dosing.

Main Results:

• ADS051 was found to be safe and well-tolerated across all dose groups.
• The most common adverse event was constipation, reported by 5.0% of participants at the 1,500 mg dose.
• High concentrations of ADS051 were recovered in stool (10%-24% of dose), with minimal systemic absorption (quantifiable in only 2 blood samples) and low urinary excretion (<0.035% of dose).

Conclusions:

• ADS051 demonstrated a favorable safety and tolerability profile in healthy volunteers.
• The drug achieved high concentrations in stool with limited systemic exposure, suggesting local action in the gut.
• ADS051 holds potential as a safe and effective locally acting, neutrophil-targeting therapy for ulcerative colitis.