Eddystone Rock will miss the Betfred Cambridgeshire at Newmarket due to an unsatisfactory scope.
The Johnny Murtagh-trained four-year-old had emerged as a leading contender for the first leg of the autumn double after winning three of his last four starts, most recently in the mud at Tipperary.
Murtagh posted on Twitter: " Eddystone Rock non-runner in Cambridgeshire on Saturday unsatisfactory scope this morning #disappointed."
Eddystone Rock was not the only major defector at the declaration stage, with ante-post favourite Sacred Act and Keystroke not among the final field of 35 runners.
Frankie Dettori, who was initially set to ride Sacred Act, has switched to the Jeremy Noseda-trained Bravo Zolo.
The weights are headed by GM Hopkins, the mount of Ryan Moore, and 2013 Cambridgeshire hero Educate.
Bronze Angel, winner in 2012 and 2014, and last year's victor Third Time Lucky also feature.
Other runners include Spark Plug, Very Talented, Banksea and Examiner.