The CIA lost trace of Jason Bourne’s whereabouts in Moscow six weeks ago. Meanwhile, Aaron Cross is a government operative assigned to Operation Outcome, a Department of Defense black operation program using experimental pills known as “chems” to enhance the physical and mental abilities of their users. Aaron is assigned to Alaska for a training exercise, where he must survive weather extremes and traverse rugged terrain in order to arrive at a remote cabin. The cabin is operated by an exiled Outcome operative, Number Three, who informs Aaron that he has broken the mission record by two days. Reporter Simon Ross of The Guardian, who has been investigating the CIA programs Treadstone and Blackbriar, is assassinated at London Waterloo station. When the illegal adaptation of the programs is exposed by Jason, the FBI and the Senate Select Committee on Intelligence investigate CIA Director Ezra Kramer, Deputy Director Pamela Landy, Blackbriar supervisor Noah Vosen and Treadstone medical director Dr. Albert Hirsch. After the mayhem in New York and Jason’s escape, Kramer requests help from Mark Turso, a retired United States Navy admiral, who runs the National Research Assay Group (NRAG). Turso informs Eric Byer, a retired Air Force colonel overseeing NRAG’s research and development of various clandestine enhancement programs used by the CIA and Defense. Byer discovers a potentially scandalous video on the Internet showing Hirsch socializing with Dr. Dan Hillcott, Outcome’s medical director. To prevent the Senate investigation from learning about Outcome, Byer orders everyone associated with the program killed. He sees the sacrifice as acceptable in order to protect NRAG’s next-generation “Beta programs”, including the supersoldier program LARX. Predator, an unmanned aerial vehicle (UAV) like the one featured in Legacy Byer deploys a drone to eliminate Outcome agents Number Three and Five (Aaron) in Alaska. Aaron hears the drone’s approach and leaves moments before a missile destroys the cabin with Number Three inside. Aaron removes the Radio-frequency identification implanted in his thigh and force-feeds it to a wolf which is then blown up by a missile, tricking Byer into believing Aaron is dead. Hirsch dies of an apparent heart attack before he can testify before the Senate. Dr. Donald Foite, a researcher at a bio-genetics laboratory, uses a pistol to kill all but one of his top-level colleagues employed by Outcome. When security guards enter his lab, Foite turns his gun on himself, leaving biochemist Dr. Marta Shearing as the sole survivor. Meanwhile, other Outcome agents are eliminated when their handlers give them poisoned chems. When four elite “D-Track” assassins ambush Marta at her country house and attempt to fake her suicide, they are eliminated by Aaron. He saves her life as she is his last link to the chems so that he can retain his enhanced capabilities and avoid withdrawal symptoms. Marta reveals that Cross has been genetically modified by a tailored virus to retain the physical benefits without needing the green chems anymore. He still requires regular doses of blue chems to maintain his intelligence, but he is running out. Aaron confides to her that he is Private First Class Kenneth J. Kitsom (reportedly killed by a roadside bomb in the Iraq War) and that his recruiter added 12 points to his IQ, enabling Aaron to meet the United States Army’s requirements. Without his enhanced intelligence, Aaron believes they stand no chance of survival. Aaron and Marta travel to Manila, where the chems are manufactured, to try to infect him with another virus so he will not need the blue chems. Aaron and Marta bluff their way into the chem factory. Marta injects Aaron with the live virus stems. Byer alerts the factory security, but Aaron and Marta evade capture. Byer orders LARX-03, a chemically-brainwashed supersoldier, to track down and kill them. Aaron recovers from the flu-like symptoms but hallucinates about his Outcome training. Police surround their shelter while Marta is buying medicine; she warns Aaron by screaming. Aaron rescues her and steals a motorbike. They are pursued by both the police and LARX-03. After a lengthy chase through the streets and marketplaces of Manila to Marikina, they lose the police, but not the assassin. Both Aaron and LARX-03 are wounded by bullets. LARX-03 is killed when Marta causes his motorcycle to crash into a pillar. Marta persuades a Filipino boatman to help them escape by sea. They sail away, while back in New York, Vosen lies to the Senate that Landy committed treason by trying to sell Treadstone secrets to the press and by assisting Jason, the only reason why Blackbriar existed.
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