Last year's winner Le Beau Bai has been ruled out of next week's Coral Welsh National after suffering an injury in routine work on the gallops.
Richard Lee's nine-year-old looked set to return to Chepstow with a major chance after enjoying a fine preparation for the Grade Three marathon, including a win over hurdles at Ffos Las.
Le Beau Bai was also set to get his favoured heavy conditions following the rain that has swept the country this week, making his injury a bitter pill to swallow for his connections.
Lee said: "It's hugely disappointing but these things happen unfortunately and the sooner it becomes public knowledge the better.
"I don't know how bad the injury is as I'm at Towcester at the moment, but it's a high hind limb injury of some sort.
"Hopefully he can be saved, but how bad it is I just don't know."