Tackling Alzheimer's and its kinfolk

OSAKA, Japan & SOUTH SAN FRANCISCO, Calif.—A deal announced Jan. 5 between Takeda Pharmaceutical Co. Ltd. and Denali Therapeutics will put Denali’s Antibody Transport Vehicle platform, which is designed to enhance blood-brain barrier penetration for neurological therapeutics, to work on three specified product candidates for treating neurodegenerative diseases. Each program in the strategic option and collaboration agreement is directed to a genetically validated target for neurodegenerative disorders, including Alzheimer’s disease and other indications.

Under the terms of the deal, Takeda will make an initial payment to Denali of $150 million, consisting of a mix of upfront cash payments and the purchase of Denali equity. In addition, Denali is eligible to receive development and commercial milestone payments, including potentially $90 million in preclinical milestones and opt-in payments.

“This partnership further exemplifies Takeda’s continued commitment to developing genetically validated therapies for neurodegenerative diseases through an enhanced portfolio comprised of new modalities,” said Emiliangelo Ratti, head of the Neuroscience Therapy Area at Takeda. “We are excited to partner with the Denali team, whose innovative technology is uniquely poised to deliver the next generation of antibody therapeutics for patients.”

Denali will be responsible for all development activities and costs prior to the filing of an Investigational New Drug application for each of the three programs. Takeda has the option to co-develop and co-commercialize each of the three programs. If Takeda exercises that option, the parties will then jointly conduct clinical development and share all costs equally, with Denali leading early clinical development activities and Takeda taking the lead on late-stage clinical development activities.

“We are impressed with Takeda’s commitment to developing treatments for difficult-to-treat neurodegenerative diseases and look forward to partnering with them to bring medicines to patients,” said Denali CEO Dr. Ryan Watts. “Takeda has a great track record of partnering with biotech firms in addition to unique development expertise and a strong global commercial presence.”

If any of the products gain regulatory approval, Takeda and Denali will jointly commercialize those products in the United States and China, while Takeda will enjoy exclusive commercialization rights in all other markets—both parties will share global profits equally.

On the same day the deal with Denali was announced, Takeda also released news that it intends to acquire TiGenix NV, a biopharmaceutical company developing novel stem cell therapies for serious medical conditions. The acquisition agreement has the unanimous support of the TiGenix board of directors, including its CEO, and is said to be “a natural extension of an existing partnership agreement between Takeda and TiGenix, which aims to bring new treatment options to patients with gastrointestinal disorders.”

The transaction value would be approximately €520 million on a fully diluted basis, or about $620.3 million.

“As a leader in gastroenterology, Takeda recognizes the complex physical, emotional and social barriers that people living with fistulizing Crohn’s disease experience,” said Andrew Plump, chief medical and scientific officer for Takeda. “Limited treatment options exist today, and I believe we can be most effective in serving this population by working in collaboration with partners whose unique skill sets allow us to more efficiently explore innovative approaches, including stem cell therapies. I have had the opportunity to work alongside the TiGenix team throughout our collaboration and know that we have shared goals and varied but complementary expertise. I am thrilled at the prospect of welcoming them as part of our organization.”

In July 2016, Takeda and TiGenix entered into an exclusive ex-U.S. license, development and commercialization agreement for Cx601, the leading investigational therapy in TiGenix’s pipeline. Cx601 is a suspension of allogeneic expanded adipose-derived stem cells locally administered for the treatment of complex perianal fistulas in patients with non-active/mildly active luminal Crohn’s disease, who have had an inadequate response to at least one conventional or biologic therapy.

A decision from the European Medicines Agency on the marketing authorization for Cx601 in the European Union is expected in the first half of this year.

A global, pivotal Phase 3 trial investigating Cx601 for the treatment of complex perianal fistulas in patients with non-active/mildly active luminal Crohn’s disease has been initiated for U.S. registration. Takeda is also exploring the steps required for regulatory filing of Cx601 for patients in Japan, Canada and emerging markets.