TOP1288 in UC

TOP1288 is our lead candidate for the treatment of ulcerative colitis (UC), a chronic, relapsing inflammatory condition effecting over 2 million people worldwide. It usually manifests with bloody diarrhoea and abdominal pain while in the long-term it increases the risk of developing colorectal cancer.  First-line therapy fails in an estimated 50% of patients and despite current treatments, approximately 15% of patients end up requiring a partial or total colectomy (surgical removal of the colon). Please see our Disease Focus section for more information on this disease.

Better by design

Our approach has been to develop TOP1288, a relatively large ‘small molecule’ which targets several important kinases (P38, Src family kinases (Src & Lck) and Syk) involved in the signalling cascade in inflammatory diseases. TOP1228 has demonstrated an excellent activity profile in vitro and in vivo, including in models of human disease, and it has been shown to synergistically inhibit key pathways involved in innate and adaptive immunity.

Through its specific structural properties, TOP1288 has been designed to act locally in the gastrointestinal (GI) tract when given either orally or rectally, with only limited systemic absorption. This means that the body’s exposure to the drug is minimized, thereby avoiding or reducing the side-effects seen with currently available treatments. As a result, we anticipate that the product could be can used both in the short-term to achieve disease emission and also in the long term as a maintenance therapy.

Clinical development

UC provides an ideal opportunity for the delivery of topical treatments to the site of the disease, as agents can be administered either by rectal or oral delivery although the latter has much greater patient acceptance and convenience. Our development strategy is to demonstrate proof of concept for TOP1288 via rectal administration to determine the effect the drug has on the disease when administered directly to the colon. In parallel, we are developing an oral formulation of TOP1288, as the intended commercial presentation.

An oral formulation of TOP1288, the intended commercial presentation of the drug, has completed a successful Phase 1 study. The trial was a randomised, double-blind, placebo-controlled 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.

TopiVert also recently completed a Phase 2a proof-of-concept (POC) study of the rectal formulation in patients with moderate-to-severe UC.  High response rates were seen in both active and placebo arms such that the results are uninterpretable.

For more information on the studies, please visit


TopiVert is now planning a Phase 2 POC study with the oral formulation, and will seek an industry partner to complete the development and commercialisation of TOP1288 worldwide.