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Almost two decades after the underwater carnage in Deep Blue Sea (1999), the shark conservationist, Misty Calhoun, accepts the pharmaceutical billionaire Carl Durant's invitation to join his team of marine biologists in the Akhelios Complex: a sophisticated research facility in the middle of the ocean. Intent on succeeding where the ambitious Aquatica Project has failed, instead, Durant makes the same mistake, and genetically enhances the brains of his bull shark specimens with a highly experimental formula, transforming them into smarter and deadlier predators. Now, one of them is pregnant. Can the team survive the onslaught of the super-sharks?