Kathy Najimy and Annette O’Toole are among the thesps lined up to star in the world preem production of A.R. Gurney’s “Heresy,” set to bow in an Off Broadway run at downtown Gotham’s Flea Theater.

Najimy (“King of the Hill”) and O’Toole (“Smallville”) are joined by a cast that includes Reg E. Cathey (“The Wire”), Ariel Woodiwiss, Steve Mellor and two members of the Flea’s acting company, Tommy Crawford and Danny Rivera. Flea a.d. Jim Simpson directs.

In the play, set in the near future, Najimy and Mellor portray parents whose son, a protestor, has been taken into custody by Homeland Security, pleading their case with Pontius Pilate (Cathey).

“Heresy” reps the latest of several plays by Gurney (“Love Letters,” “Sylvia”) to debut at the Flea, including “Mrs. Farnsworth,” “Office Hours” and “O Jerusalem.”

“Heresy” begins previews Sept. 29 ahead of an Oct. 11 opening. Flea season also will include a stint by Alan Rickman in the Beckett-inspired “Krapp Hour” as well as a potential stage outing for helmer Joel Schumacher, directing a new play by Beau Willimon.