Theravance Biopharma, Inc. (NASDAQ: TBPH) ("Theravance Biopharma" or the "Company") today announced dosing of the first patient in a Phase 2 clinical trial of TD-1473 in patients with Crohn's disease. TD-1473 is a novel, potent, orally administered and gut-selective pan-Janus kinase (JAK) inhibitor in development as a treatment for multiple inflammatory intestinal diseases. In contrast to other oral JAK inhibitors under development for inflammatory bowel disease, TD-1473 is specifically designed to act locally at the site of inflammation in the intestinal wall with minimal systemic exposure.
The Phase 2 study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of TD-1473 in approximately 160 patients with moderately to severely active Crohn's disease. Patients will be randomized to receive one of two active doses of TD-1473 or placebo once daily for up to 12 weeks. The primary endpoint of the study is improvement in Crohn's Disease Activity Index (CDAI) score measured at 12 weeks. The study also includes an active treatment extension phase that will include those patients who complete the 12-week induction phase.
"We are excited to advance our gut-selective JAK inhibitor program into its first Phase 2 trial as we believe TD-1473 can produce potentially transformative therapeutic activity against inflammatory intestinal diseases. Clinical data generated to date provide us with confidence as we begin a comprehensive late-stage development program for TD-1473, encompassing this study in Crohn's disease and an upcoming Phase 2b/3 trial in patients with ulcerative colitis," said Brett Haumann, MD, Chief Medical Officer at Theravance Biopharma. "We are hopeful that findings from these trials will demonstrate desired therapeutic results in these indications with an acceptable safety profile, and further confirm the localization of biological activity within the intestine with minimal systemic exposure."
Theravance Biopharma previously announced positive results from a Phase 1b clinical trial of TD-1473 in 40 patients with ulcerative colitis, demonstrating localized biological activity and minimal systemic exposure, as well as a favorable safety and tolerability profile. These results formed the basis for progressing TD-1473 into larger clinical trials in Crohn's disease and ulcerative colitis. Based on these positive Phase 1b data and successful dialogues with U.S. Food and Drug Administration (FDA) and European Medicines Authority (EMA) regarding the late-stage development plan, Theravance Biopharma also plans to initiate a Phase 2b/3 induction and maintenance study of TD-1473 in patients with ulcerative colitis in late 2018 or early 2019.
About Theravance Biopharma and Janssen Strategic Collaboration
Theravance Biopharma and Janssen Biotech, Inc. have entered into a global co-development and commercialization agreement for TD-1473 and related back-up compounds for inflammatory intestinal diseases, including ulcerative colitis and Crohn's disease. Under the terms of the agreement, Theravance Biopharma received an upfront payment of $100 million and is eligible to receive up to an additional $900 million in potential payments, if Janssen elects to remain in the collaboration following the completion of certain Phase 2 activities. Theravance Biopharma together with Janssen will jointly develop and commercialize TD-1473 in inflammatory intestinal diseases, with the two companies sharing profits in the US and expenses related to a potential Phase 3 program.
About Gut-Selective Pan-Janus (JAK) Kinase Inhibition
JAK inhibitors function by inhibiting the activity of one or more of the Janus kinase family of enzymes (JAK1, JAK2, JAK3, TYK2) that play a key role in cytokine signaling. Inhibiting these JAK enzymes interferes with the JAK/STAT signaling pathway and, in turn, modulates the activity of a wide range of pro-inflammatory cytokines. JAK inhibitors are currently approved for the treatment of diseases such as rheumatoid arthritis and myelofibrosis, and have demonstrated therapeutic benefit for patients with ulcerative colitis. However, these products are known to have side effects associated with their systemic exposure.
TD-1473 is an internally-discovered JAK inhibitor that has demonstrated a high affinity for each of the JAK family of enzymes. Importantly, TD-1473 is a gut-selective treatment specifically designed to distribute adequately and predominantly to the tissues of the intestinal tract, treating inflammation in those tissues while minimizing its systemic exposure. Theravance Biopharma is focused on utilizing targeted JAK inhibitors for potential treatment of a range of inflammatory intestinal diseases including ulcerative colitis and Crohn's disease, which affect roughly 900,000 and 700,000 patients in the United States, respectively.