The Knights are coming off a win in round 12 and a bye in round 13 so they should be refreshed and ready to take the game up to the premiers.
Penrith went about their business in clinical fashion against the Bulldogs and got the job done even without six of their big-name stars on Origin duty.
How many of those players back up after Wednesday's series opener remains to be seen but such is the Panthers' depth that they will go in as clear favourites to rack up a 13th win of the season.
The Knights have Kalyn Ponga and Dane Gagai on show for Queensland and both are likely to back up should they get through the game with a clean bill of health.
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The Rundown
Team news
Knights: The Knights are 1-17 with no late changes. A boost for Newcastle with utility Kurt Mann returning from an ankle injury for his first game since round seven, pushing Phoenix Crossland to the reserves. Jacob Saifiti moves into the starting side to replace his brother Daniel, who is out with a knee injury. Leo Thompson comes onto the bench.
Skipper Kalyn Ponga and Dane Gagai will back up from Wednesday night's Origin opener.
Panthers: Coach Ivan Cleary will miss the match for medical reasons but there are no late changes on the field on game day. Nathan Cleary, Liam Martin, Stephen Crichton, Brian To'o and Jarome Luai will all back up from Origin but Isaah Yeo will be rested, with Matt Eisenhuth taking his spot in the starting side and Spencer Leniu joining the bench. Robert Jennings is 18th man.
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Key match-up
Jacob Saifiti v James Fisher-Harris: Having earned selection in Brad Fittler's NSW squad, Saifiti should be walking taller as he returns to his club team for a showdown with the competition's benchmark team. Now a veteran of 110 games in the NRL, Saifiti knows what is required to take the fight up to Fisher-Harris, Moses Leota and co. In 12 appearances this year, JFH has churned out 147 metres per game, 15 tackle breaks and made 30 tackles a game, emphasising his importance to the premiers with a string of high-quality performances.
Stat Attack
The Knights have won just one of five games at McDonald Jones Stadium this season and been outscored 159 to 48 across those five matches. The losses came against Manly (30-6), Parramatta (39-2), Melbourne (50-2) and Brisbane (36-12). The Knights won five of nine games at McDonald Jones last season.
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