Johnson & Johnson’s Janssen Biotech will codevelop Theravance’s TD-1473 and related backup compounds for inflammatory intestinal diseases, including ulcerative colitis and Crohn's disease, the companies said today, through a collaboration that could generate up to $1 billion-plus for Theravance.

TD-1473 is a novel, potent, orally administered, and intestinally restricted pan-Janus kinase (JAK) inhibitor that according to Theravance has the potential to treat a variety of inflammatory intestinal diseases. TD-1473 is specifically designed to act directly at the site of inflammation in the intestinal wall, thereby limiting systemic exposure—an advantage, the company says, over other oral JAK inhibitors being developed for inflammatory bowel disease.

Among those JAK inhibitors is the Gilead Sciences/Galapagos candidate filgotinib, which is in Phase III trials for Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, and AbbVie’s upadacitinib (ABT-494), which is in Phase II studies in Crohn’s and ulcerative colitis, in addition to Phase III in rheumatoid arthritis.

In August, Theravance trumpeted positive Phase Ib data from the first cohort of patients treated with TD-1473. The second and third cohorts are set to be completed in the first half of this year.

In addition to minimal systemic exposure, and clinical response after only four weeks of therapy, Theravance reported:

  • 7 of 10 patients receiving TD-1473 experienced a 1-point or greater reduction in Mayo rectal bleeding subscore, compared to 1 of 3 patients receiving placebo
  • 3 of 10 patients receiving TD-1473 showed a 1-point or greater reduction in Mayo endoscopic subscore, compared to none of the placebo patients.
  • 2 of 10 patients receiving TD-1473 showed evidence of mucosal healing, based on Mayo endoscopic subscore, compared to none of the placebo patients.

“Internally, we have been very excited about the potential of TD-1473 to serve as a transformational medicine designed to offer the proven therapeutic activity of JAK inhibitors without the safety concerns associated with systemic JAK exposure,” Theravance chairman and CEO Rick E Winningham said in his company’s statement on the collaboration.

Studies Set for Second Half of 2018

During the second half of 2018, Theravance plans to launch a Phase II study of TD-1473 in Crohn's disease—these timelines will be accelerated due to the Janssen collaboration, Theravance said in a presentation to investors this morning—and a larger Phase IIb/III adaptive design induction and maintenance study of TD-1473 in ulcerative colitis.

Upon completion of the Phase II Crohn's study and the Phase IIb induction portion of the ulcerative colitis study, Janssen can opt to enter into an exclusive license agreement—in return for paying Theravance $200 million.

Janssen also agreed to pay Theravance up to $700 million in payments tied to achieving development and commercialization milestones, as well as double-digit tiered royalties on ex-U.S. sales, under the companies’ global codevelopment and commercialization agreement.

That agreement gives Janssen a two-thirds share of profits in the U.S. and expenses related to a potential Phase III program (67% to Janssen and 33% to Theravance).  

Janssen would lead later-stage development of TD-1473 in Crohn's disease after Phase II, while Theravance will lead development of TD-1473 in ulcerative colitis through completion of the Phase 2b/3 program.

If TD-1473 reaches the market, Theravance has the option to cocommercialize in the U.S., while Janssen would have sole commercialization responsibilities in the rest of the world. 

“We look forward to advancing this promising, oral, drug candidate through clinical development as we continue to address the significant unmet needs of people living with Crohn's disease and ulcerative colitis around the world,” added Scott E. Plevy, M.D., VP, disease area leader, inflammatory bowel disease, Janssen Research & Development, in a separate Janssen statement. 

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