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He was born in Faenza, the son of Gian Galeazzo I Manfredi, and inherited his lands in Romagna, ruling first in association with his brother, Carlo, and later alone. From 1439 he was also lord of Imola and Modigliana. He was married with Bianchina Trinci, daughter of Niccolò, lord of Foligno, until her assassination in 1441. The following year he remarried with Agnese, daughter of Guidantonio I da Montefeltro, lord of Urbino.