Cobitolimod's Way of Reducing Inflammation in Intestine Revealed

Cobitolimod modifies the immune system in ulcerative colitis by acting on Toll-like receptor 9 (TLR9) and balancing the mucosal Th17/Treg cell response, according to the study in the Journal of Crohns and Colitis (JCC).

The drug has recently met the primary endpoint in the phase IIb dose optimisation study CONDUCT as a novel therapy for moderate to severe ulcerative colitis with an outstanding combination of efficacy and safety.

‘Cobitolimod may benefit patients with ulcerative colitis and crohn's disease by inducing immunomodulatory effects in the colonic mucosa.’
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Ulcerative colitis is a debilitating chronic disease caused by inflammation of the large intestine.

Accumulating evidence indicates that an imbalance between T helper 17 (Th17) and T regulatory (Treg) cells and their associated cytokines creates a pro-inflammatory state in ulcerative colitis.

The scientific data now published in JCC demonstrate that cobitolimod mediates immunomodulatory effects both in an experimental colitis model as well as in blood and tissue samples of ulcerative colitis patients leading to a rebalanced Th17/Treg cell immune response.

"Cobitolimod is an innovative drug candidate with a unique mechanism of action for the treatment of ulcerative colitis. The highly interesting data presented in this paper clearly show that cobitolimod can induce immunomodulatory effects in the colonic mucosa leading to decreased inflammation in a murine model of colitis", said Professor Markus Neurath of the University of Erlangen-Nürnberg.

"The fact that cobitolimod was able to balance the Th17/Treg cell response both in a mouse model, in vitro in cells from UC patients and in patients treated with cobitolimod in a clinical study demonstrates the robustness of the results. Cobitolimod represents a truly exciting first-in-class approach to targeted treatment of colonic inflammation."

Treatment with cobitolimod demonstrated therapeutic efficacy in the standard experimental model of colitis. At the same time, Th17 cells and pro-inflammatory IL17 and IL6 cytokines were significantly decreased, and Treg cells and IL10 positive immune cells were significantly increased after cobitolimod treatment.

In line with these data, cobitolimod significantly decreased IL17 and significantly increased the expression of the anti-inflammatory cytokine IL10 in immune cells from ulcerative colitis patients in vitro.

Ulcerative Colitis
Ulcerative colitis is characterized by bouts of diarrhea, bleeding per rectum and pain, which remits and relapses. Fulminant colitis is a possibility, which may require colectomy.

Furthermore, analysis of colon biopsies of ulcerative colitis patients taken before and four weeks after administration of cobitolimod showed a significant induction of IL10 positive and a pronounced reduction of IL17 positive immune cells after cobitolimod treatment in patients responding to cobitolimod, which was not observed in placebo treated patients.

In addition, Treg cells were significantly increased in the colon upon treatment with cobitolimod. Besides IL10 producing Treg cells, cobitolimod could also induce anti-inflammatory IL10 producing wound healing macrophages in vitro in cells from UC patients.

These data were obtained in collaboration with the University of Erlangen-Nürnberg in Germany, and has previously been presented at the congress of the European Crohn's and Colitis Organisation.

"We are very pleased with the publication of these results, which provide a deeper understanding of how cobitolimod mediates its anti-inflammatory effects.

That JCC also chooses to highlight the data in their podcast, shows that there is a great interest from the scientific community," said Peter Zerhouni, CEO of InDex Pharmaceuticals. "This supporting mechanistic data fits very nicely with the successful clinical results obtained with cobitolimod in our phase IIb study CONDUCT."

Source-Medindia