TOP1288 targets several important enzymes including P38, Src, Lck and Syk — all of which are involved in the underlying molecular process of inflammatory diseases. Preclinical studies have demonstrated that TOP1228 is effective in mice models of human disease, and can block key pathways involved in immunity.
Due to its specific structure, this investigative therapy targets the gastrointestinal tract with limited off-target effects. This makes it more efficient, safe and tolerable than currently available therapies.
The TV03 Phase 1 study (NCT03071081) evaluated the safety and tolerability in healthy volunteers of an oral formulation of TOP1288, as well as its availability and distribution in the body.
Researchers divided 36 participants into six groups to receive either a single dose of TOP1288 (200mg or 1g), seven-day dosing of TOP1288 (1g or less), or placebo. They then collected tissue samples from the colon to directly measure drug delivery. Finally, they analyzed biomarkers to target specificity and determine how the therapy affected participants.
The scientists found that TOP1288 goes directly and specifically to the colon, with little systemic drug dispersion in the body. It also significnaty changed several biomarker responses; overall, researchers found the therapy safe and well tolerated when administered orally, confirming data of previous studies.
“Using an innovative trial design, we have successfully demonstrated that the investigative drug can be delivered into the colon tissue at pharmacologically relevant concentrations,” Ajay Duggal, TopiVert’s chief medical officer, said in a press release.
In a parallel, proof-of-mechanism study (NCT02463045) in ulcerative colitis patients, researchers evaluated TOP1288’s effects compared to placebo when administrated as a liquid enema. Clinically relevant changes from baseline were reported in those patients who received TOP1288. But those results were inconclusive, due to a large response in the placebo arm.
Based on these findings, TopiVert plans to move the oral TOP1288 into a proof-of-concept study in ulcerative colitis.
“These results put TopiVert in a unique position in the development of oral topical anti-inflammatories for treatment of IBD,” said Simon Travis, professor of clinical gastroenterology at England’s University of Oxford. “Although efficacy still needs to be established, the results obtained strongly support progression to the next stages of development.”