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Despite preliminary observations by long-range probes, the first-manned expedition by the Federation was conducted by the Cleopatra's Needle, a vessel chartered by the University of Alpha Centauri in the late 2350s. Shortly afterwards, the USS Mary Kingsley, under the command of Captain Onna Karapleedeez, was the first Starfleet vessel to enter the region. Captain Donald Varley was also somewhat familiar with the region, and provided maps of the Reach to his friend Jean-Luc Picard. (TNG novel: The Buried Age)
The Scorpius Reach remained largely unexplored into the 2370s. In 2383, the region was one of several considered by Captain Timothy Sinclair as the target of the USS Pendragon's new exploration directive. Ultimately, however, the Pendragon was embarked on a survey of the Great Rift and the galactic rim. (Star Trek: Pendragon: "Not Home Yet)