Chimica Oggi-Chemistry Today
Agro FOOD Industry Hi Tech
Clinical development of the toll-like receptor 9 agonist DIMS0150 in chronic active ulcerative colitis patients
Chief Medical Officer, InDex Pharmaceuticals AB

KEYWORDS: Toll-like receptors, ulcerative colitis, therapy, oligonucleotide.


Ulcerative colitis (UC) is an immune-mediated condition characterized by a continuous mucosal inflammation of the colon, which might be caused from the dysregulated balance between commensal enteric flora and the gut-associated immune system. A proportion of patients do not respond to available therapies becoming treatment refractory and requiring surgical intervention and therefore novel treatment strategies are needed (1-3).
One of the ways that host discerns foreign from self-antigen is through pattern recognition receptors (PRRs), which recognize specific molecular patterns of pathogens. One group of PRRs consists of Toll-like receptors (TLRs) with variable specificities for sensing microbial products. One of these receptors, TLR-9, recognizes exclusively bacterial DNA and has over the years received growing interest as a potential target for therapeutic intervention in the treatment of UC. It could be shown that TLR-9 activation prevents development of mucosal inflammation and promotes wound healing in several models of experimental colitis (4-6).


DIMS0150 is a fully synthetic DNA based 19 mer oligodeoxyribonucleotide that acts as a TLR-9 agonist, developed by our company. This DNA sequence elicits its immunomodulatory effects through specific target cells, i.e., antigen presenting cells such as dendritic cells and B cells, as well as intestinal epithelial cells. A large number of in vitro and in vivo studies have shown that DIMS0150 exerts immunomodulatory as well as anti-inflammatory effects. The immunomodulating effects of DIMS0150 are accomplished through the induction of e.g. interferons type I and Interleukin 10 (IL-10) from these target cells.
DIMS0150 is currently under clinical evaluation in the indication ulcerative colitis (UC) for its potential ability to induce clinical remission in UC patients who are chronic active treatment refractory. DIMS0150 has been assessed in a total of four clinical trials and under named patient use, comprising a total of 249 patients that have received at least one dose. Local administration of DIMS0150 onto the colonic mucosa has shown positive effects in chronic active ulcerative colitis patients with respect to efficacy and safety.
In the latest clinical study the efficacy of DIMS0150 was evaluated in a randomized, double blind, placebo-controlled, multicentre, pan-european trial (the “COLLECT” study) in 131 patients with moderate to severe active ulcerative. Patients were randomly assigned to receive two single doses of DIMS0150 (30 mg) or placebo (in a 2:1 ratio) administered topically to the inflamed mucosa at baseline and after 4 weeks. Already at week 4 significantly more DIMS0150 treated patients achieved symptomatic remission compared to placebo. Furthermore, the proportion of patients in clinical remission with mucosal healing at week 4 was also higher in the DIMS0150 group versus the placebo group. At later time points e.g. at week 8 or 12 sustained efficacy was observed. In this clinical study a total of 13.8% SAEs were reported across both treatment groups with 18.6% of patients in the placebo group and 11.5% patients in the Kappaproct group reporting...In order to continue reading this article please register to our website – registration is for free and no fees will be applied afterwards to download contents.

Teknoscienza Mobile
Teknoscienze - Viale Brianza 22, Milano - ITALY - P.IVA 06817720151
Teknoscienze S.r.l. © 2012 - tutti i diritti riservati - web terms & conditions - privacy - Credits