US-based Theravance Biopharma has started a Phase I clinical trial of TD-1473, a potent, orally administered GI-targeted pan-Janus kinase (JAK) inhibitor, to treat inflammatory intestinal diseases.

TD-1473 is an internally discovered JAK inhibitor that has showed a high affinity for each of the JAK family of enzymes: JAK1, JAK2, JAK3 and TYK2.

In inhibiting these enzymes, TD-1473 interferes with the JAK / STAT signaling pathway, and modulates the activity of a range of pro-inflammatory cytokines.

"Our targeted approach seeks to maximise the therapeutic potential of JAK inhibition."

TD-1473 is primarily a GI-targeted treatment, designed to be distributed adequately and exclusively to GI tract tissues, and minimise systemic exposure.

The primary objective of the Phase I trial is to evaluate the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of TD-1473 in healthy subjects.

The trial’s secondary objective will be the characterisation of pharmacokinetics related to TD-1473, which will help determine the amount of TD-1473 that enters systemic circulation after administration.

Theravance Research and Development senior vice-president Mathai Mammen said: "In the past month we have advanced two novel, potentially best-in-class programmes from our internal discovery and research engine into Phase I clinical trials.

"Our targeted approach seeks to maximise the therapeutic potential of JAK inhibition in the affected areas of the gastrointestinal tract, while minimising the safety and tolerability concerns associated with systemic JAK blockade.

"Our ability to create a pan-JAK inhibitor that is targeted specifically to the GI tract may enable us to offer patients with ulcerative colitis and other inflammatory intestinal diseases a treatment option that significantly improves upon currently available therapeutics."

Findings from a preclinical trial evaluating TD-1473 and tofacitinib showed that both compounds significantly reduced colitis manifestations.