So impressive when beating last year's Arc winner Torquator Tasso at Ascot in the summer highlight, a soft tissue problem means trainers William Muir and Chris Grassick will not be able to get the required work into the five-year-old.
Also the winner of last year's Coronation Cup at Epsom, Pyledriver had been around the 14/1 mark for the ParisLongchamp showpiece.
"He's had a slight setback and we're gutted," said Muir.
"I can't gallop him tomorrow or next week, we can keep going but I can't gallop him, otherwise he could end up being off for longer.
"It's very minor and it's a toss of a coin, but we had to make the decision. If I can't have him at 100 per cent like he was for the King George, there's no point in going for a race like the Arc.
"We're distraught, as we wanted to be in there, but that's life and we have to get on with it, we have to do right by him."
He went on: "It's very minor and my vet said this time next week he could be 100 per cent.
"The plan now will be to see if we can still go for the Breeders' Cup or the Japan Cup, whichever one, and then Hong Kong and the Sheema Classic.
"You don't get many good horses like this but he hasn't missed many (races). This is not like his last problem when he was sore, this is very small and as long as it goes the right way, we are in business - just not in time for the Arc."