Denali Therapeutics will use F-star’s Modular Antibody Technology™ to develop antibodies for delivering drugs across the blood–brain barrier into the central nervous system (CNS), the companies said today, through a collaboration that could generate up to $1 billion-plus for F-star.

The collaboration is intended to generate constant Fc domains with antigen-binding activity (Fcabs™) that can bind to transporters in the blood–brain barrier.

Through the platform, the companies said, Fcabs can be inserted rapidly into any existing antibody to generate a full-sized bispecific antibody (mAb² ™) that can both cross the blood–brain barrier and bind to specific CNS targets. Denali and F-star reason that the mechanism could treat neurological diseases by acting on specific targets in the brain.

Denali has agreed to pay an F-star asset-centric vehicle $6 million upfront and has the option to nominate a prespecified number of Fcab targets for development. F-star Gamma Ltd. will also receive research funding and unspecified technical milestone payments from Denali.

Denali also has the option to acquire F-star Gamma before the launch of the first Phase I clinical trial in return for aggregate exercise and milestone payments to F-star Gamma shareholders of up to $450 million, the companies said.

If Denali elects not to exercise its option to acquire F-star Gamma, it can license an undisclosed prespecified number of mAb² based on each Fcab generated by F-star Gamma. In return, F-star would receive license fees, development, regulatory, and commercial milestones payments totalling $1 billion—as well as tiered royalties on product sales.

The deal is F-star's second option-to-buy, asset-centric deal. The first deal came in 2014, when Bristol-Myers Squibb signed an exclusive option for up to $475 million to acquire another F-star entity, F-star Alpha, and gain worldwide rights to its lead asset and first clinical compound, the human epidermal growth factor receptor 2 (HER2)-positive breast cancer candidate FS102, indicated for patients refractory or unresponsive to HER2 treatments. F-star could generate a potential $475 million upon the start of Phase IIb studies for FS102.

Headquartered in Cambridge, U.K., F-star specializes in developing immuno-oncology bispecific antibody therapeutics selected for their potential to transform the treatment of cancer.

The collaboration was one in a series of alliances and other actions disclosed today by Denali. The company said that it closed in June on a $130 million Series B equity financing, and also:

  • Acquired Incro Pharmaceuticals to gain access to its receptor interacting protein kinase 1 (RIP1) inhibitor program, developed through a license and collaboration agreement with Harvard University.
  • Signed a license agreement with Genentech, a member of the Roche group, for exclusive global rights to develop and commercialize leucine-rich repeat kinase 2 (LRRK2) inhibitors for the treatment of Parkinson's disease.
  • Inked a research collaboration and exclusive license agreement with Washington University School of Medicine in St. Louis to develop and commercialize antibodies targeting apolipoprotein E (ApoE), a neurodegeneration-causing protein and genetic risk factor for Alzheimer's disease.
  • Signed a collaboration and option agreement with Blaze Bioscience for research on and discovery of novel blood–brain barrier-crossing therapeutics at the Fred Hutchinson Cancer Research Center.