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In 2012, at the age of nineteen, she met Jack Spheer and began working with him to try and find a cure for cancer and other diseases using nanotechnology.After three years, Lena and Jack fell in love with each other and started a romantic relationship; Lena was given the opportunity to travel on the suborbital spacecraft Venture but had to back out at the last minute due to an important business meeting regarding the renaming of her company.
However, she urged that she had nothing to do with it, simply wanting to start anew outside of her family, giving the two a flash drive with information on the Venture's destroyed oscillator that a subsidiary of her company had manufactured; she didn’t knew it then, but the words that Lena imparted to the Kryptonian cousins, prior to handing them the stored digital data, will have a lasting effect on Kara herself and influencing the other woman into making a huge decision.
Despite this, she is currently unaware that the two are one-and-the-same.
And in a similar vein, Lena also befriended Samantha Arias, whom she was acquainted to from long prior, and likewise unaware that the latter is also secretly the Worldkiller, Reign.
Later, Lena comes to Cat Co and invites Kara to a charity event to raise funds for a children's hospital as she was practically the only bonafide friend Lena had in National City; and in extending the invite, Lena acquaints herself with Kara’s new co-worker “Mike Matthews”.
The next day, Lena — who presumably deduced a close correspondence between her friend and the city's alien protector after noticing the connection between Supergirl's taking down of Sinclair's fight club operations not long after she herself handed the coordinates to Kara — came to Kara's apartment (where she catches Alex talking with Kara and learning the fact that they are adoptive sisters) and asked her to arrange a meeting with Supergirl, so, in the evening, Kara arrives at Lena's L-Corp office in the guise of Supergirl.