ADS051 is the first and only MRP2 / FPR1 inhibitor to demonstrate favorable safety and tolerability with signals of clinical efficacy with relief from disruptive symptoms of inflammatory bowel disease in a multiple ascending dose (MAD) study of moderately to severely active Ulcerative Colitis (UC) patients in relapse
ADS051 was demonstrated to be safe in a single ascending dose (SAD) study in healthy volunteers across five dosing cohorts
CONCORD, Mass., March 6, 2025 /PRNewswire/ — Adiso Therapeutics, Inc. announced the publication of the results of two Phase 1 studies, which showed that healthy subjects and ulcerative colitis (UC) patients given oral doses of ADS051, a novel modulator of neutrophils being developed for Inflammatory Bowel Disease (IBD), could be safely administered and well-tolerated in IBD patients. These studies showed consistent safety and tolerability of ADS051 with highly encouraging signals of clinical response as determined by Mayo Endoscopic Scoring blinded to the investigator. Data from the two trials has been published in the American Journal of Gastroenterology, the official journal of the American College of Gastroenterology (ACG).
The first of the two publications presents the results from the single ascending dose (SAD) trial of ADS051. This trial was the intensive first in human study of ADS051 across five (5) dosing cohorts of healthy subjects and included a deep-reaching pharmacokinetic analysis of this first and only modulator of neutrophils. There were no dose-limiting toxicities, serious adverse events (AEs), or trial discontinuation due to AEs. Pharmacokinetic data demonstrated minimal systemic absorption of ADS051, with the majority of drug excreted in the stool as expected. There was no clinical evidence of adverse immunosuppressive activity.
The second publication presents the results of a multiple ascending dose (MAD) study of ADS051 in patients with moderately to severely active UC. The MAD study included three (3) placebo controlled dosing cohorts, measuring signals of clinical response using assessments typical for later stage studies, such as Mayo Endoscopic Scoring which included Clinical Remission (CR), Endoscopic Improvement (EI), and Endoscopic Response (ER). The study also looked at neutrophil-related markers of inflammation and histologic assessment. As detailed in the publication, this study achieved its primary endpoint of safety and tolerability with encouraging signs of efficacy across multiple outcome measures.
“The SAD publication documents the successful completion of a very important first step in establishing patient safety. The completion of the study provided an understanding and foundation for safe dosing of ADS051 prior to exposure in patients with IBD,” said Adam Cheifetz, M.D., Director, Center for Inflammatory Bowel Disease, Beth Israel Lahey Health, Beth Israel Deaconess Medical Center, Harvard Medical School Teaching Hospital.
“UC is an inflammatory disease with complex underlying biology. We are now amid a rapidly expanding therapeutic landscape of treatment options for individuals with IBD, yet ADS051 is different and represents a unique therapeutic approach of neutrophil modulation,” said Jessica Allegretti, MD, MPH., Crohn’s and Colitis Center, Associate Professor of Medicine, Harvard Medical School, Gastroenterology, Hepatology and Endoscopy, Internal Medicine, Brigham and Women’s Hospital. “Participants in the multiple ascending dose (MAD) trial with moderately to severely active UC were repeatedly dosed with ADS051. Highly favorable signals of pharmacologic activity and clinical benefit were seen over a relatively short 28-day period. These Phase 1b MAD data indicate that ADS051 may represent an important therapeutic advancement as a safe and effective, once-daily oral therapy for patients with UC.” ADS051 is a novel, oral, gut-restricted, small molecule consisting of an active moiety or warhead, covalently linked to a 2,000 molecular weight polyethylene glycol (PEG). ADS051 inhibits two neutrophil-related receptors, multidrug resistant protein 2 (MRP2) which activates hepoxilin A3 (HXA3) neutrophil recruitment or transmigration and formyl peptide receptor 1 (FPR1), a known GPCR found on the surface of neutrophils, important for activation and signaling recruitment. Due to the design of ADS051, it largely remains in the colonic lumen, avoiding wide-spread systemic exposure and subsequent T-cell activation or general immunosuppression. Unlike currently available therapies, ADS051 is intended to positively affect neutrophil-mediated tissue damage, a hallmark of IBD pathology.
The ADS051 data generated from these two studies has been submitted to the United States (U.S.) Food and Drug Administration (FDA) within an end-of-Phase 1 meeting. Adiso is currently planning a Phase 2 trial for the treatment of moderately to severely active UC in adults.
Publication Links: Small-Molecule Neutrophil Modulator ADS051 is Safe and Well-Tolerated in a Phase 1 Single Ascending Dose Study (Open Press), Safety, Pharmacokinetics, and Clinical Efficacy of ADS051, a Neutrophil Modulator, in Ulcerative Colitis: Results of a Randomized Phase 1b Trial (Open Press)
About ADS051
ADS051 is a novel, oral, gut-restricted, small molecule that blocks multidrug resistant protein 2 (MRP2)/hepoxilin A3 (HXA3) and formyl peptide receptor 1 (FPR1) mediated neutrophil epithelial transmigration and activation in human cell-based systems. Its lack of both systemic exposure and blockage of T cell activation is intended to limit general immunosuppression. Unlike currently available therapies, it addresses neutrophil-mediated tissue damage, a hallmark of UC pathology. In a Phase 1b MAD study in patients with moderate to severe ulcerative colitis, ADS051 demonstrated favorable safety and tolerability administered orally, once daily, in patients with moderate-to-severe UC. PK data demonstrated that ADS051 is gut-restricted, as designed, with minimal systemic drug exposure. ADS051 efficacy measures indicate encouraging signals of pharmacologic activity and clinical benefit versus placebo after 28 days of treatment. The Phase 1b MAD data indicate that ADS051 may be an important therapeutic advancement as a safe and effective, once-daily oral therapy for patients with UC. Adiso is currently pursuing additional investigation of ADS051 in a larger Phase 2 clinical study.
About Adiso
Adiso is a clinical-stage biopharmaceutical company dedicated to improving the health of patients suffering from debilitating inflammatory diseases. This dedication is epitomized by our lead clinical candidates, ADS051, an oral gut-restricted modulator of neutrophil trafficking and activation via inhibition of MRP2 and FPR1 for the treatment of inflammatory bowel disease; and ADS032, a dual NLRP1/NLRP3 inflammasome inhibitor initially being developed for inflammatory diseases of the lung. Adiso has built these development programs upon a rich history of institutional and academic collaboration, including the University of Massachusetts Chan Medical School, the Hudson Institute of Medical Sciences Centre for Innate Immunity and Infectious Diseases in Australia, the University of Edinburgh Centre for Inflammation Research and the University College Cork, Ireland, the APC Microbiome Institute. For more information, please visit www.adisotx.com or our LinkedIn page www.linkedin.com/company/adisotx/
Refer to: Scott Megaffin; pr@adisotx.com (media)
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