Set roughly one year after the events of Pokémon Eclipse, Twilight Sparkle has opened her School of Friendship (SoF) to the creatures of Equestria and beyond. After a successful first year, the school expands to the world of Pokémon in the newly-created commune of Poniose Town outside of Lumiose City in the Kalos region. There, Equestrians can experience the Pokémon world first-hand while humans are able to integrate themselves with their otherworldly neighbors.

Together, Twilight and SoF Pokémon teacher Sam Brier begin inviting select human students to Poniose Town with the intent to enroll them into the school, among whom are teenaged trainers Mikael Wallström and Jacqui Sweeney. The two form a friendship with each other as well as a motley group of Equestrian students and trainers-in-training, all of whom are excited to take part in Chaser Battles, a new, more-extreme style of Pokémon battle that is taking the Pokémon world by storm.

Meanwhile, the Champions of each Pokémon League all over the world, including Alolan champion Alice Brier, are systematically defeated from their titles in quick succession. The newest Champions quickly begin sponsoring select Chaser Battle teams to dominate the Pokémon world and push back against Equestria, whose ideals of love and friendship they believe to be invading on their ideals of power and overwhelming strength. Sam and Alice begin working with Mikael, Jacqui, and their new friends to mold them into the best trainers possible to battle against the new Champions and their chasers and maintain peace between the two worlds.

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