We have nonexclusive clinical collaboration agreements with all manufacturers of direct Factor Xa inhibitors, in which they provide cash payments, as well as input on the development and regulatory approval of andexanet as an antidote to their direct Factor Xa inhibitors in the U.S., E.U., and Japan. Excluding Japan, Portola has retained all commercial rights to andexanet alfa on a worldwide basis.
As part of our Phase 2 proof-of-concept studies, we entered into three separate agreements to include cohorts dosed with the approved Factor Xa inhibitors apixaban (Eliquis®, Bristol-Myers Squibb and Pfizer), rivaroxaban (XARELTO®, Bayer and Janssen) and edoxaban (Savaysa®, Daiichi-Sankyo). New agreements covering Phase 3 development through U.S. and E.U. regulatory approvals for each agent were entered into after the completion of the Phase 2 studies. In addition, we have also entered into an agreement with Daiichi Sankyo in Germany focused on the expansion of the ANNEXA-4 study in bleeding patients.
Development and commercialization of andexanet alfa as a universal antidote for Factor Xa inhibitors in Japan is fully supported by collaboration partners. Specifically, Bristol-Myers Squibb and Pfizer are responsible for development, regulatory and commercial activities in Japan. Separately, we entered clinical collaboration agreements with Bayer and Daiichi Sankyo to include their Factor Xa inhibitors, rivaroxaban and edoxaban, respectively, in the Japanese clinical development program.
In December 2016, we licensed worldwide rights for the development and commercialization of cerdulatinib in topical applications beyond oncology to Dermavant Sciences. We retain full rights to all nontopical formulations, including oral formulations.
Syk Selective Inhibitors
In May 2015, we announced a collaboration with Ora, Inc. for the development of our highly selective Syk inhibitor PRT2761 in ophthalmic diseases.