Adiso Therapeutics, Inc. today announced a publication in FEBS Open Bio describing preclinical characterization of ADS051, a first-in-class, oral, gut-restricted, small molecule modulator of neutrophil trafficking and activation.
| Company plans to initiate Phase 2a dose ranging clinical trial for patients with ulcerative colitis in 4Q 2023 CONCORD, Mass., July 13, 2023 /PRNewswire/ -- Adiso Therapeutics, Inc., a clinical-stage biotechnology company creating medicines to treat inflammatory diseases, today announced a publication in FEBS Open Bio describing preclinical characterization of ADS051, a first-in-class, oral, gut-restricted, small molecule modulator of neutrophil trafficking and activation.
An improved understanding of the mechanisms by which epithelial cells control neutrophil migration has long been a goal of researchers. Neutrophil modulation holds the promise of tremendous patient benefit in the understanding of biological processes and development of new therapeutic agents. The extent of neutrophil infiltration is a hallmark in the pathogenesis and clinical course of inflammatory disorders of the gastrointestinal tract. Clinical development of ADS051 in neutrophil-mediated disorders, particularly ulcerative colitis, is supported by its ability to modulate neutrophil trafficking and activation as described in the publication. Adiso designed ADS051 to specifically target two proteins in the colonic lumen: MRP2 and FPR1. MRP2 (multi drug resistance protein 2) effluxes the potent neutrophil chemoattractant, hepoxilin A3 (HXA3) into the lumen during episodes of inflammation in the gut, resulting in recruitment of neutrophils into the colonic lumen. In addition to modulating the trafficking of neutrophils, ADS051 also modulates activation of neutrophils via the second targeted protein, FPR1 (formyl peptide receptor 1). FPR1 is a G-protein-coupled receptor (GPCR) expressed on the surface of neutrophils that, when exposed to formylated peptides derived from resident bacteria or mitochondria released from damaged tissue, results in their activation. Activated neutrophils degranulate, resulting in the release of pro-inflammatory cytokines and tissue damaging factors. Due to its ability to block both neutrophil accumulation and activation in the colonic lumen, ADS051 represents a novel therapeutic approach to reducing the colonic inflammation in diseases such as ulcerative colitis (UC). This publication describes the rational design of ADS051, its activity in human cell-based assays and its gut restriction and safety when dosed orally in animal studies. “Intestinal neutrophil activity increases substantially in active ulcerative colitis, driving tissue damage in the colon. To date, neutrophil modulation has been largely overlooked as a therapeutic goal. We believe that targeting neutrophils and their inflammatory mediators is an opportunity that should be explored to identify new effective medicines. ADS051 is a mechanistically differentiated small molecule with the potential to modulate neutrophil activity in UC, thereby abolishing the destructive inflammation with associated acute and chronic tissue damage without compromising host-defense. Many current UC therapies can result in systemic immunosuppression and unwanted side-effects. We are excited to advance clinical development of ADS051, an oral, first-in-class, gut-restricted therapeutic to address the neutrophilic inflammation associated with UC,” said Chris Murphy, Vice President of R&D at Adiso. ADS051 gut restriction, safety and tolerability after oral dosing has been demonstrated in a healthy subject Phase 1a clinical study. Results from a recently completed Phase 1b multiple ascending dose trial in UC patients will be presented at an upcoming major medical conference. The combined Phase 1a/1b data packages have enabled Adiso to submit an End of Phase 1 meeting request to the Food and Drug Administration, as the Company intends to pursue a Phase 2 development program in patients with moderate to severe ulcerate colitis in 4Q 2023. The FEBS Open Bio article can be found here: Development of ADS051, an oral, gut‐restricted, small molecule neutrophil modulator for the treatment of neutrophil‐mediated inflammatory diseases - Murphy - FEBS Open Bio - Wiley Online Library About ADS051 ADS051 is an oral, gut-restricted, small molecule modulator of neutrophil trafficking and activation for the treatment of moderate-to-severe ulcerative colitis. Unlike currently available therapies, it addresses neutrophil-mediated tissue damage, a hallmark of UC pathology. In a healthy volunteer SAD study, and in a Phase 1b MAD study, oral doses of ADS051 were safe and well-tolerated and largely restricted to the gut with limited systemic exposure. About Adiso: Adiso Therapeutics, Inc. is a clinical-stage biopharmaceutical company dedicated to improving the lives of patients and their families by creating novel and differentiated medicines to treat inflammatory diseases. The company’s lead programs exemplify ‘healthruption’ (disruption in healthcare and drug development) with novel mechanisms of action and a distinct approach to precision treatment of inflammatory diseases. ADS051 is an oral, gut-restricted modulator of neutrophil trafficking and activation for the treatment of ulcerative colitis that has just completed a Phase 1b MAD clinical trial and will be moving into Phase 2 development later this year. Adiso is also developing ADS032, a novel small molecule that acts as a dual inflammasome inhibitor (NLRP3 & NLRP1) and is in advanced pre-clinical development for the treatment of respiratory and dermal inflammation. For more information, please visit www.adisotx.com or our LinkedIn page. Contacts Adiso Therapeutics, Inc.
SOURCE Adiso Therapeutics |
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