Delayed-release oral tablets of brilacidin for ulcerative colitis (UC) was found delivered and dispersed into the colon, and was well-tolerated in healthy volunteers in a Phase 1 trial, announced the treatment’s developer, Innovation Pharmaceuticals.

Brilacidin is a small molecule that belongs to a new class of compounds known as defensin-mimetics. It mimics antimicrobial peptides (small proteins) that are naturally produced in the body and serve as the “front-line” defence, or innate immune system, against harmful microbes. For this reason, brilacidin can kill microbes quickly, decreasing the likelihood of drug resistance, and also has immunomodulatory properties that lessen inflammation and promote wound healing.

Of note, some studies have suggested that patients with inflammatory bowel disease (IBD) are deficient in antimicrobial peptides called defensins and other proteins called mucins, which are important for the body’s natural barrier in the gastrointestinal tract. Therefore, brilacidin is thought to potentially compensate for this deficiency.

The Phase 1 trial (NCT04240223), launched in January this year, enrolled nine healthy volunteers, six of whom received brilacidin and three took a placebo. Participants were divided into three dosing groups, within which two participants received one of three doses of brilacidin (50 mg, 100 mg, or 200 mg), and one subject received a placebo.

The study was the first to test delayed-release tablets of brilacidin for colonic delivery — a formulation based on BDD Pharma‘s OralogiK technology — in collaboration with Innovation.

In addition to assessing brilacidin’s safety, tolerability, and pharmacokinetic properties (the availability and elimination of the therapy from the body), the investigators traced the compound delivery to the colon using an advanced imaging technology based on gamma scintigraphy, which was developed by BDD Pharma.

This technique requires brilacidin to be radio-labeled, allowing researchers to follow the tablet through the gastrointestinal tract and see how it is released in the colon. The method can also measure how long a compound stays in the colon, and how fast it disintegrates, adding to the information about brilacidin pharmacokinetic properties.

Using this technique, brilacidin was seen to be released at the initial (ascending) part of the colon in four of the six subjects, and in the portion of the small intestine that communicates with the colon (terminal ileum and ileocecal junction) in the remaining two patients. Following the release, the compound was dispersed throughout the colon.

Blood samples taken over the first 24 hours after dosing showed no traces of brilacidin absorption into the blood, indicating that it stays contained within the colon, Innovation stated. More analyses are ongoing to confirm this finding.

In a prior Phase 2 study, brilacidin, which was delivered into the rectum through an enema, led to clinical or partial disease remission in most patients included in the study who had ulcerative proctitis/ulcerative proctosigmoiditis, a type of ulcerative colitis.

Now, preliminary results from the oral brilacifin trial suggest that dosing can be safely increased if the therapy is delivered via targeted release tablets.

“BDD are delighted to have successfully completed the first oral dosing study of brilacidin, which has demonstrated the capability of its OralogiK Technology to deliver a brilacidin formulation to the colon,” Howard Stevens, PhD, the study’s principal investigator and chairman of BDD Pharma, said in a press release.

“The treatments were well-tolerated with no treatment related adverse events,” he added. “Although absorption of brilacidin was not observed from analysis of plasma concentrations, this was not unexpected and may indeed be a desirable attribute for a drug that acts by virtue of its local effect on inflamed mucosal surfaces within the lower GI [gastrintestinal] tract. We look forward to further collaboration with Innovation Pharma as this exciting drug progresses through development.”

In addition, Innovation plans to develop foam and/or gel formulations of brilacidin to treat ulcerative proctitis/ulcerative proctosigmoiditis.