Her role has been split into two, creating the jobs of a senior marketing manager and head of PR, although no one has yet been appointed for either post.
The region, which covers the cities of Nottingham, Derby, Lincoln and Leicester, was home to 30,000 new businesses last year, but must increase the number by 4,000 every year to meet its target of becoming one of the top 20 European Union regions for GDP and 'gross value added', said O'Reilly.
The agency is charged with helping to improve the region's GDP, attracting inward investment, regenerating local communities, and encouraging businesses and their staff to take up training opportunities.
Industries prominent in the area include engineering, textile technology and food technology, with a fifth of England's food produced in the region, according to the EMDA.
The new head of PR will report to strategy and comms director Abby Johnson-Brennan and will manage a team of four.
O'Reilly, who has been at the agency for four years, said: 'The role has grown. You cannot do both roles effectively.'
The senior marketing manager will report to the head of PR.
The agency appointed former Toyota chairman Brian Jackson to its chairman role in December, and previous deputy CEO Jeff Moore has been promoted to chief executive, starting in the job two weeks ago.