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The Clone Wars have exploded across the galaxy as Republic forces and Separatists struggle to gain the upper hand. But while the Jedi generals work tirelessly to defeat Count Dooku and his rebels, Supreme Chancellor Palpatine is hatching his own dark plans. The Separatists have launched a sneak attack on Coruscant. Obi-Wan Kenobi, wounded in battle, insists that Anakin Skywalker and his rookie Padawan, Ahsoka, leave on a risky mission against General Grievous.

The Lizard is wreaking havoc throughout the Everglades, as he seeks a cure for his dual identity as the reptilian villain and the human scientist Dr. Curt Connors - the result of an experiment gone horribly wrong. Spidey's attempts to halt the Lizard's rampage lead him to a web of intrigue and danger that may spell the destruction of a space-shuttle launch. The action heats up as Venom, the alien symbiote who wants Spider-Man dead, arrives, targets the Lizard for death, and won't let anyone stand in his way!