James Grayson will make his first Saints start when he lines up at fly-half in the clash with Sale Sharks at the AJ Bell Stadium on Saturday evening (kick-off 5.30pm).
The 19-year-old made his debut from the bench in the opening-day defeat to Saracens back in September and has gone on to make a further five appearances as a replacement.
But he gets the nod from the off at Sale, coming into the team in place of Stephen Myler, who is on the bench.
There are several further changes to the back line after last Saturday's 30-15 defeat at Worcester Warriors, with JP Estelles and Ben Foden coming in on the wing.
They replace Ken Pisi and Tom Collins, who is on the bench, while Tom Stephenson and Rory Hutchinson are selected at centre with Luther Burrell (concussion) and Rob Horne (suspended) missing.
In the pack, Jamal Ford-Robinson comes in for Kieran Brookes, who has been ruled out for six weeks after fracturing his hand at Sixways last Saturday.
Paul Hill takes Ford-Robinson's place on the bench.
Sam Dickinson again skippers the side from the second row.
Sale Sharks: Haley; Solomona, James, Jennings, Yarde; O'Connor, De Klerk; Harrison, Webber, John; Evans, Ostrikov; Ross (c), B Curry, Strauss.
Replacements: Jones, Flynn, Aulika, Nott, Neild, Van Rensburg, Cliff, Addison.
Saints: Mallinder; Estelles, Hutchinson, Stephenson, Foden; Grayson, Reinach; Waller, Haywood, Ford-Robinson; Paterson, Dickinson(c); Wood, Gibson, Harrison.
Replacements: Marshall, Van Wyk, Hill, Moon, Eadie, Groom, Myler, Collins.