He was elected Bishop of Mileto on September 18, 1411. He was transferred to the see of Ravello on February 15, 1413; to the see of Melfi on January 25, 1418; and then to the see of Ancona on March 6, 1419. On October 19, 1422, the see of Umana was united to that of Ancona.
Agnensi then moved to Rome, becoming apostolic treasurer. From August 1426 to April 1427, he was the papal governor of the Duchy of Spoleto and the March of Ancona. He and Barthélémy Texier, Master of the Order of Preachers, were sent to the see of Iesi to deal with the heretics of the Fraticelli. 
On March 26, 1442, Pope Eugene IV named him his vicar in spiritualibus and governor of Rome, a post he held until 1447. He was also the apostolic administrator of the see of Canna from June 16, 1445 until May 25, 1449. In September 1447, he became governor of Bologna. He was Vice-Chancellor of the Holy Roman Church during the papacy of Eugene IV.
Pope Nicholas V made him a cardinal in the consistory of December 20, 1448. He received the titular church of Sant'Eusebio on January 3, 1449, and the red hat on January 6, 1449. He was Camerlengo of the Sacred College of Cardinals from October 27, 1449 until 1450.
|Catholic Church titles|
|Camerlengo of the Sacred College of Cardinals
Isidore of Kiev