Cheltenham Festival winner Dynaste will miss the 2015 meeting and has been ruled out for the season by trainer David Pipe.
Last year's Ryanair Chase victor strained a hind leg when finishing third at the track last month.
In his absence, Don Cossack is 4-1 favourite for the 12 March race.
Dynaste, aged nine, has won seven of his 23 career starts and was second to Silviniaco Conti in the King George VI Chase at Kempton in December.
"It's nothing serious but he's too good to risk and the chances are good for him to be back for a full season come next autumn," Pipe told the Racing Post.
Pipe's stable jockey Tom Scudamore said: "It's very disappointing and he'll leave a big hole as far as our Cheltenham is concerned, that's for sure."