The Ditcheat handler is aiming As De Me at the Randox Health Becher Handicap Chase and Touch Kick for the Virgin Bet Grand Sefton Handicap Chase.
As De Mee, owned by Andy Stewart's family and actress Dame Judi Dench, is proven over the obstacles, having won the Grand Sefton in 2016.
Nicholls expects the nine-year-old to put up a bold display following a prep run over hurdles at Cheltenham last month after being off the track since February.
"As De Mee has won over the fences before. He had a nice run over hurdles the other day. He is a big 33-1 each way shot for the race I would say," he said.
There are two past winners among 26 five-day acceptors - Vieux Lion Rouge (2016) and Walk In The Mill (2018) - plus the 2017 Grand National hero, One For Arthur.
The weights are headed on 11st 12lb by Gordon Elliott's Alpha Des Obeaux, the sole Irish possible, and Ballyoptic from Nigel Twiston-Davies' stable.
Others in the mix include Abolitionist, Le Breuil, Mysteree, Mulcahys Hill, Rathlin Rose, Regal Flow, Vintage Clouds and Wandrin Star.
Nicholls pins his hopes on Touch Kick in the Grand Sefton, for which there were 19 five-day confirmations.
"Touch Kick won nicely at Fakenham the other day and we purposely left him for this race," he said.
"I think he will run really well. I expect him to love those fences and Mr (Trevor) Hemmings (owner) loves to have runners over the Grand National fences there."
The top two in the weights, Casablanca Mix and Gold Present are trained by Nicky Henderson.
Ultragold, winner of the Topham Chase in 2017 and 2018, could bid for another triumph over the big fences.
There is a likely French raider in the Louisa Carberry-trained It's Jennifer while among others of interest are Flying Angel, Kayf Adventure and Killaro Boy.
Native River and Might Bite, who fought out the finish for the Cheltenham Gold Cup in 2018, feature among eight entries for the Virgin Bets Price Boost Many Clouds Chase.
Colin Tizzard's Native River got the verdict over the Henderson runner that day and both could be action for the first time last season's blue riband in which they were fourth and pulled up respectively.
Henderson has also put in Top Notch, a course winner over hurdles last month.
The Brian Ellison-trained Definitly Red could for a third successive win in this race, although he is also still in the Becher at this stage.
Aso, Black Corton, Kildisart and Outlander make up the octet.
