• 8 January 2018
    TopiVert announces positive results from the Phase 1 study with its oral formulation of TOP1288 for the treatment of ulcerative colitis

    TopiVert Pharma Ltd (“TopiVert” or the “Company”), a clinical-stage biotechnology company developing Narrow Spectrum Kinase Inhibitors (NSKIs) as novel, locally-acting medicines for the treatment of chronic inflammatory gastrointestinal and ocular diseases, today announces positive data from its Phase 1 study (TV03) with its oral formulation of TOP1288 for the treatment of ulcerative colitis (UC).

    UC is a form of inflammatory bowel disease (IBD) affecting the colon. As many as 40% of patients fail to respond to current drug therapy, which is also often poorly tolerated, and around 15% of patients may still require surgical removal of the colon to manage the disease. TOP1288 is a NSKI developed by TopiVert that targets several important kinases in inflammatory cells, leading to synergistic inhibition of key signalling pathways involved in innate and adaptive immunity. TOP1288 also has very low systemic bioavailability such that its activity is confined to the site of active disease in UC patients and thus provides an improved safety and tolerability profile.

    TV03 was a randomised, double-blind, placebo-controlled Phase 1 study to assess safety, tolerability, pharmacokinetics and pharmacodynamic responses to single and multiple oral doses of TOP1288. Employing an innovative trial design, individual subjects received serial sigmoidoscopies so that multiple colon biopsies could be obtained to allow the direct measurement of tissue drug concentrations, as well as markers of target engagement and pharmacodynamic responses, from colon tissue.

    The results demonstrated that TOP1288 was being delivered to the colon with drug detected in tissue biopsies up to 36 hours after last dose. In addition, dose-dependent positive effects on markers of target engagement and biomarker responses were seen (in cells taken from colon tissue), indicating that the measured concentrations were pharmacologically relevant. TOP1288 was also found to be safe and well tolerated when administered orally with minimal systemic absorption being noted, confirming results from prior studies.

    In parallel, a proof of mechanism study in UC patients comparing TOP1288 and placebo, both delivered as a liquid enema, has also reported. Clinically relevant changes from baseline were seen in the TOP1288 arm for all endpoints but due to a large response in the placebo arm, including for centrally read endoscopic endpoints, the efficacy assessment was uninterpretable.

    Based upon the strong data from the TV03 study, TopiVert is preparing to progress the oral TOP1288 formulation into a proof of concept study in UC. 

    Ajay Duggal, TopiVert’s Chief Medical Officer, commented: “We are delighted with the clinical progress made with our TOP1630 and TOP1288 NSKI programmes in ophthalmology and IBD respectively. Our recently reported strong proof of concept data for TOP1630 in dry eye syndrome validates our NSKI technology in the treatment of inflammatory disease. For our IBD program, using an innovative trial design, we have successfully demonstrated that drug can be delivered into the colon tissue at pharmacologically relevant concentrations. This is an exciting time for TopiVert as we look forward to progressing the clinical development of both our lead programmes in areas of high unmet medical need.”

    Professor Simon Travis, (Professor of Clinical Gastroenterology, University of Oxford), commented: “These results put TopiVert in a unique position in the development of oral topical anti-inflammatories for treatment of IBD. The colon biomarker and PK data generated with the oral formulation of TOP1288, together with the fact that there was minimal systemic absorption, demonstrate effects through truly local action. This phenomenon has not been demonstrated before. Although efficacy still needs to be established, the results obtained strongly support progression to the next stages of development”