Jul 5, 2016

http://www.genengnews.com/gen-news-h...ment/81252910/

TiGenix has sold to Takeda ex-U.S. rights to its stem cell treatment Cx601 for complex perianal fistulas in patients with Crohn's disease—an up-to-€390 million ($435 million)-plus deal reflecting what the Belgian biotech called a shift of resources toward its allogeneic stem cell platforms.

As part of that shift, TiGenix said, it was withdrawing its European marketing authorization application for ChondroCelect®, an autologous cell therapy product for cartilage repair of the knee. Instead, TiGenix will refocus on its upcoming Phase III U.S. trial for Cx601, as well as its other clinical stage assets.

Cx601 is a suspension of allogeneic adipose-derived stem cells (eASC) injected intralesionally. In March, TiGenix submitted a marketing authorization application to the European Medicines Agency for Cx601, based on positive 24-week results of the ADMIRE-CD Phase III clinical trial. More recently, TiGenix announced top-line 52-week data that it said confirmed the efficacy and safety of a single injection of Cx601.

Following marketing authorization in Europe, Takeda will become the marketing authorization holder and will oversee all commercialization and regulatory activities. Takeda will also be responsible for additional development activities of Cx601 for the indication of complex perianal fistulas in Crohn’s disease.

TiGenix will retain the rights to develop Cx601 in new indications—and will continue to hold U.S. rights to the allogenic stem cell therapy.

"This agreement further provides TiGenix with the financial strength to move forward with the clinical development of Cx601 in the U.S.,” TiGenix CEO Eduardo Bravo said in a statement, adding that the U.S. represents approximately half of the world’s Crohn’s market.

Added Marc Princen, Takeda’s president of Europe and Canada: “This collaboration and the addition of Cx601 to our portfolio highlights Takeda’s commitment to the development of treatments to improve the health of people living with gastroenterological disorders, leveraging our expertise in inflammatory bowel disease and Crohn’s specifically.”

Takeda’s therapeutic areas include gastrointestinal as well as “general medicine,” including oncology, cardiovascular and metabolic, central nervous system, respiratory and immunology, and vaccines.

The licensing deal with TiGenix is Takeda’s second gastrointestinal-focused initiative in less than a month. On June 8, Takeda inked a global license, development and commercialization agreement to develop Theravance Biopharma’s TD-8954, a Phase II drug candidate for gastrointestinal motility disorders, including enteral feeding intolerance (EFI). The transaction could generate up to $125 million-plus for Theravance.

In return for ex-U.S. rights to Cx601, Takeda agreed to pay TiGenix €25 million ($28 million) cash upfront, up to €355 million ($396 million) in payments tied to achieving regulatory and sales milestones, and double-digit royalties on net sales by Takeda. In addition, Takeda agreed to make an equity investment of €10 million ($11 million) in the share capital of TiGenix within the next 12 months.

The first anticipated milestone payment TiGenix would receive is €15 million ($16.7 million) upon obtaining marketing authorization of Cx601 in the European Economic Area.

TiGenix blamed “a difficult competitive landscape” due to a chilly regulatory environment in Europe for autologous chondrocyte-based cell therapy products, as well as a lack of reimbursement in key European countries, for its decision to withdraw its marketing application for ChondroCelect, which has been approved for reimbursement in The Netherlands and Spain.

The company said it has agreed with Sobi to an early termination of their existing commercial relationship, which in 2014 entailed the licensing by TiGenix of exclusive marketing and distribution rights for ChondroCelect in Europe (excluding Finland), the Middle East, and North Africa to Sobi. TiGenix also said it will end a ChondroCelect-related manufacturing agreement with PharmaCell.