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 20% 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.

A Phase 1 clinical trial of TOP1288 delivered rectally was completed in 2016. This drug was found to be safe and well tolerated in healthy subjects and also in a small cohort of patients with ulcerative colitis. 

TopiVert has initiated a Phase 2a proof-of-concept (POC) study of the rectal formulation in patients with moderate-to-severe UC.  This study is designed to assess the efficacy and safety of the product when presented directly to site of active disease. In parallel, an oral formulation of TOP1288, the intended commercial presentation of the drug, is currently being evaluated in a Phase 1 study. Both studies are expected to report in the second half of 2017.

For more information on the studies, please visit


Upon the successful completion of the POC for the rectal formulation and the Phase 1 data for the oral formulation, TopiVert plans to seek an industry partner to complete the development and commercialisation of TOP1288 worldwide.