Simonsig has been ruled out of the Tingle Creek Chase at Sandown on Saturday with lameness.
The grey, twice a winner at the Cheltenham Festival, was all set for his first run over fences since the 2013 Arkle Trophy having returned from over two years off with a fine run over hurdles at Aintree last month.
Trainer Nicky Henderson said: "Simonsig is not running tomorrow, he's lame.
“He was okay, Barry (Geraghty) came in and rode him and he schooled, but unfortunately he is lame tonight.
“I honestly don’t know why – it is so, so cruel. I’m desperately sorry for Ronnie (Bartlett, owner), he has waited over two years to get him here.
“He schooled this morning and he was fine. It’s horrible, especially given we had got a prep run into him that had gone so well.”
It is a further blow for the race, with Irish star Un De Sceaux ruled out by Willie Mullins on Wednesday, when he was described as a "little flat".
Henderson will still be represented in the Grade One showpiece by Josses Hill.
