Conan's place on the bench has been taken by Cian Prendergast, who started in Ireland's tournament-opening loss to champions France.
Ireland coach Andy Farrell had already responded to last week's unconvincing 20-13 win over Italy by making several changes to his starting side, with Jack Crowley picked at fly-half in place of Sam Prendergast.
Tadhg Furlong, Jamison Gibson-Park, Tadhg Beirne and Josh van der Flier have also been brought into the starting line-up.
Both England and Ireland have won one and lost one of their opening two matches, with England now looking to bounce back from last week's 31-20 defeat by Scotland at Murrayfield that ended their 12-game winning streak.
England captain Maro Itoje wins his 100th cap on Saturday, with back-row forward Henry Pollock making his first Test start.
Revised teams for the Six Nations international between England and Ireland at Twickenham, London, on Saturday (kick-off 14:10 GMT):
Teams (15-1)
England
Freddie Steward; Tommy Freeman, Ollie Lawrence, Fraser Dingwall, Henry Arundell; George Ford, Alex Mitchell; Henry Pollock, Ben Earl, Tom Curry; Ollie Chessum, Maro Itoje (capt); Joe Heyes, Luke Cowan-Dickie, Ellis Genge
Replacements: Jamie George, Bevan Rodd, Trevor Davison, Alex Coles, Guy Pepper, Sam Underhill, Jack van Poortvliet, Marcus Smith
Coach: Steve Borthwick (ENG)
Ireland
Jamie Osborne; Robert Baloucoune, Garry Ringrose, Stuart McCloskey, James Lowe; Jack Crowley, Jamison Gibson-Park; Caelan Doris (capt), Josh van der Flier, Tadhg Beirne; James Ryan, Joe McCarthy; Tadhg Furlong, Dan Sheehan, Jeremy Loughman
Replacements: Ronan Kelleher, Tom O'Toole, Finlay Bealham, Nick Timoney, Cian Prendergast, Craig Casey, Ciaran Frawley, Tommy O'Brien
Coach: Andy Farrell (ENG)
Referee: Andrea Piardi (ITA)