A middle of the night arrival by unmarked helicopters with secret cargo from the Middle East places the facility on high alert. When the unspeakable happens and the mysterious Subject Alpha escapes with Dr. Kathryn Ryan as a hostage, the military is forced to work with Indian Affairs agent Frank Ironhorse Whitman and his team to track the dangerous creature through Crow territory. Archaeological evidence suggests their adversary is an aged old enemy...

Van Etten, a pharmaceutical entrepreneur, tests drugs on bull sharks in hopes to extract their antibodies to cure human diseases. Before he can continue with his experiment, he tries to enlist Misty Calhoun, a shark conservationist, and other scientists to lead and endorse this project. The drug-enhanced sharks quickly begin to adapt and learn new hunting skills. The humans lost control over the laboratory and now they have to fight to survive.