Novel Oral Drug Candidate Reduces Disease Activity and Lowers Inflammation in Pre-Clinical Models of Colitis

A new study published in Science Translational Medicine announced the preclinical development of a novel oral drug candidate, (S)-IBD3540, which has been shown to reduce the severity of colitis through a novel mode of action not previously targeted by currently available therapies. With support and funding from the Crohn’s & Colitis Foundation, researchers designed this drug to inhibit the function of an enzyme called gastrointestinal glutamate carboxypeptidase II (GCPII), which is increased in IBD patients. The drug would bind to GCPII in the gut and reduce the likelihood of developing adverse effects in other parts of the body. Findings from the study confirm (S)-IBD3540 can reduce disease severity and gut inflammation and protect the lining of the gut establishing the drug as a promising future novel clinical treatment of IBD patients.

This pre-clinical research will help set the path for future testing for efficacy and safety in humans.

The full study is available here.

In the study, a team led by researchers at Johns Hopkins University synthesized a novel class of GCPII inhibitors, most notably (S)-IBD354, which was found to remain gut-restricted in both normal and disease states. While the drug candidate is not yet ready for clinical use, the study results suggest that (S)-IBD3540 has the potential to reduce the symptoms of IBD, improving the quality of life for those affected by the disease.

“The robust preclinical results of (S)-IBD3540 are exciting and suggest it can reduce disease severity and inflammation, establishing this gut-restricted compound as the first GCPII inhibitor suitable for IBD clinical development,” said the research lead Barbara Slusher, Ph.D., Professor and Director of Johns Hopkins Drug Discovery. “Today’s findings bring us one step closer to developing a mechanistically novel treatment for IBD. The Crohn's & Colitis Foundation's IBD Ventures has been an invaluable partner supporting this discovery, and we look forward to their continued support.”

“This study is an important advancement that shows promising results of a potential first-in-class therapy that may enable precision medicine by using it on patients who present high levels of this enzyme,” said Andrés Hurtado-Lorenzo Ph.D.., Vice President of Translational Research & IBD Ventures at the Crohn’s & Colitis Foundation. “The Foundation’s IBD Ventures program supports and invests in novel product-oriented research and development, ultimately accelerating the development of clinical solutions for patients. The preclinical evaluation of (S)-IBD3540 shows encouraging potential, and we are excited about its potential to advance to clinical development stage.”

The Johns Hopkins University team was the first to identify GCPII inhibition as a therapeutic target for IBD in 2016. The study establishes the efficacy of lead compound (S)-IBD3540 in treating preclinical colitis models and as a highly potent GCPII inhibitor. GCPII is an enzyme minimally expressed in normal ileums and colons but markedly increased in IBD patient biopsies and preclinical rodent colitis models.

IBD Ventures was developed by the Crohn’s & Colitis Foundation to accelerate research and development of novel and differentiated products that aim to improve the quality of life for patients with IBD. Companies and academic investigators can apply. Funding up to $500,000 per project per year will be considered. In addition, funded programs will be offered accelerator resources and advising.

Contact:

Rachel Peifer

[email protected] 

About the Crohn’s & Colitis Foundation

The Crohn's & Colitis Foundation is the leading nonprofit organization focused on both research and patient support for inflammatory bowel disease (IBD), with the mission of curing Crohn's disease and ulcerative colitis and improving quality of life for the millions of Americans living with IBD. The Foundation’s work is dramatically accelerating the research process, while also providing extensive educational and support resources for patients and their families, medical professionals, and the public. For more information, visit crohnscolitisfoundation.org, call 888-694-8872, or email [email protected].