Adiso Therapeutics, Inc., a clinical-stage biotechnology company committed to creating medicines that treat inflammatory diseases and improve the lives of patients and their families, today announced positive topline data from its Phase 1b multiple ascending dose (MAD) clinical trial evaluating ADS051 (BT051) in patients with moderate-to-severe ulcerative colitis (UC). The data were presented today at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting being held October 20-25, in Vancouver, Canada.
ADS051 is a first-in-class, oral, gut-restricted, small molecule modulator of neutrophil trafficking and activation via inhibition of MRP2 and FPR1. Unlike currently available therapies, ADS051 addresses neutrophil-mediated tissue damage, a hallmark of UC pathology.
The randomized, double-blind, placebo-controlled, MAD Phase 1b study enrolled 24 moderately-to-severely active UC patients, all of whom completed the trial as planned over the 28-day treatment period (NCT05084261). ADS051 was found to be safe and well-tolerated at three dose levels (200, 800, and 3200 mg) administered orally, once daily for 28 days. PK data demonstrate that ADS051 was restricted to the gut with limited systemic exposure.
On Day 28, for pooled ADS051 participants vs. pooled placebo participants, clinical remission was achieved in 22.2% vs. 0%, endoscopic improvement (investigator blinded, centrally-read) in 33.3% vs 0%, and endoscopic response (centrally-read) (UCEIS) was achieved in 50% vs. 17%.
“We are very pleased with these positive results indicating that ADS051 clearly attained the objectives of this Phase 1b trial and may be an important therapeutic advancement as a safe and effective, once-daily oral therapy for patients with ulcerative colitis,” said Scott Megaffin, Chief Executive Officer of Adiso. “ADS051 efficacy measures reveal encouraging signals of pharmacologic activity and clinical benefit versus placebo, after 28 days of treatment. Given these findings and a recently completed positive end-of-Phase 1 FDA interaction, we plan to advance ADS051 in a Phase 2 clinical study in early 2024.”
“Despite recent therapeutic advancements in the treatment of UC, there still remains a significant unmet need for safe and efficacious therapeutic options,” said Jessica Allegretti, M.D., M.P.H Medical Director, Crohn’s and Colitis Center, Brigham & Women’s Hospital Boston and Associate Professor of Medicine, Harvard Medical School. “The results of this Phase 1b study demonstrate that not only is ADS051 safe and well-tolerated, it also may offer a potentially efficacious solution for patients with moderate-to-severe UC. I look forward to assessing this therapy further in a Phase 2 clinical study.”
The MAD clinical trial followed a healthy subject Phase 1a single ascending dose (SAD) study which demonstrated ADS051 was gut-restricted with minimal systemic drug exposure, with no dose-limiting toxicities or serious adverse events. One treatment-emergent adverse event was reported in 16.7% of patients in the pooled ADS051 group vs. 66.7% in the pooled placebo group. Safety and tolerability of the 3200-mg dose group were equivalent to the lower dose cohorts with substantially higher fecal concentrations of ADS051.
The poster detailing these findings #P0172: ADS051, an Oral, Gut-Restricted, Small Molecule Neutrophil Modulator in Patients With Moderate-To-Severe Ulcerative Colitis: Results From a Multiple Ascending Dose Study, was presented at the ACG 2023 Annual Scientific Meeting, October 22, 2023, and will be available on the Company’s website.