Favourite Pether's Moon won the Glorious Stakes at Goodwood as 2012 St Leger victor Encke finished second in his first race since a doping ban.
Pether's Moon (11-10), under Richard Hughes for trainer Richard Hannon, scored by one and a quarter lengths.
Encke was the most high-profile of 22 horses suspended from running for six months in the Godolphin scandal.
Jimmy Fortune got Ed Dunlop's 12-1 shot Red Avenger up to beat Heavy Metal in a photo finish to win the Betfred Mile.
Fortune was given a nine-day ban for excessive use of the whip.
Heavy Metal, trained by Mark Johnston, was just denied another success after winning at Ascot on Saturday.
Hannon's fast-finishing Magic City was third under Hughes, with Steeler fourth.
Steeler is another of the Godolphin 22 back in racing with Appleby after being given banned anabolic steroids under their previous trainer.
Encke had not run for 685 days and Appleby said the Irish St Leger was an option for the five-year-old, who denied Camelot the Triple Crown when winning the English version at odds of 25-1.
Hannon indicated afterwards that Pether's Moon could head for the Caulfield Cup in Australia or the Japan Cup later in the year.