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The Penrith Panthers' horror run of injuries to start the season has continued with halfback Nathan Cleary set to spend 10 weeks on the sidelines after scans revealed grade three medial ligament damage on Saturday.

Cleary failed to return to the paddock after half-time in Friday night's two-point loss to the Canterbury-Bankstown Bulldogs with initial fears the injury was only a minor 2-4 week setback for the 20-year-old.

The promising No.7 is now all but ruled out of State of Origin I contention with limited game time leading into the three-game series set to affect his chances of a representative debut.

The news comes as the Panthers battle an injury crisis early in the season having lost Sam McKendry (ACL), Tim Browne (bowel) and Dallin Watene-Zelezniak (jaw) in the past week.

Panthers utility Tyrone Peachey could replace Cleary in the halves, while Tyrone May is close to a return from a knee reconstruction in the off season.

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