Accelerating Breakthrough Discoveries into Medicines

BioMotiv Blog

Koutif Therapeutics: Exploring a Novel Approach to Treating IBD

By: Leen Ajlouni

 According to the Crohn’s and Colitis Foundation, about 1.6 million Americans have inflammatory bowel disease (IBD). Crohn’s disease and ulcerative colitis are the most common types of IBD and are characterized by chronic inflammation of the gastrointestinal (GI) tract.

The GI tract makes up part of the human digestive system. A healthy digestive system allows for food to move smoothly through and out of the body, so that the body absorbs the nutrients it needs from the food and the rest is excreted. However, in IBD patients, the GI tract is inflamed, and over time, the inflammation causes severe pain, diarrhea, and sometimes bloody stool. Because of the inflammation, the IBD patient’s body cannot absorb all the nutrients it needs, which can lead to malnutrition and other health problems like anemia.

The reason IBD patients experience constant inflammation is because of abnormal response by their body’s immune system. Normally, the cells and proteins that make up the immune system protect the body from infections caused by viruses or bacteria.  In people with IBD, however, the immune system can treat food or bacteria as foreign substances. When this happens, the body sends white blood cells and inflammatory mediators into the lining of the intestines, where they produce chronic inflammation and ulcerations. Researchers believe that once the IBD patient’s immune system is “turned on,” it does not know how to properly “turn off” at the right time. As a result, inflammation damages the intestine and causes the symptoms of IBD.

Current treatments for Crohn’s disease and ulcerative colitis primarily neutralize the inflammatory mediators produced during disease pathogenesis to reduce symptoms. Treatments include an acute intervention, followed by maintenance therapy to keep symptoms in check. Despite the advances in diagnosis and treatment, at least two-thirds of patients develop a complication requiring surgical intervention, and about 50% experience clinical relapse requiring the use of powerful drugs (such as corticosteroids). Current drugs are associated with several safety concerns such as the risk for additional infections and cancers, highlighting the large unmet medical for more innovative approaches to targeting the inflammation pathway in IBD. This is where Koutif Therapeutics steps in.

Koutif Therapeutics is changing the way inflammatory diseases are treated through the unique process of protein degradation. Protein degradation, the process that breaks down key proteins responsible for activating the inflammatory response, is one way to control inflammation. A critical step in protein degradation is the “tagging” of proteins to be degraded by enzymes called ubiquitin ligases.  Drs. Mallampalli and Chen, the founders of Koutif, have identified one of these ligases called Fbxo3, which acts to regulate the degradation of the key protein that is involved in several pro-inflammatory pathways. By regulating Fbxo3, we can break down several potent, pro-inflammatory mediators that are keeping the immune system “turned on.” This represents a novel mechanism that has the potential to treat IBD and other inflammatory conditions.

Fbxo3 has never been targeted before and represents a truly breakthrough method for treating a variety of conditions. Koutif Therapeutics filed for an investigational new drug application in January 2019 for its lead compound, and after FDA review, permission was granted to begin enrollment for clinical studies.

To learn more about Koutif and the work it’s doing to fight IBD and other diseases, including bronchiolitis obliterans syndrome, chronic obstructive pulmonary disease, acute long injury and rheumatoid arthritis, click here.


Erin Reese