In 1249, Manuel II was likely involved with the delegation from Pope Innocent IV and led by the Franciscan friar John of Parma, which arrived at the temporary Patriarchal seat in Nymphaeum in 1249 and until 1250, there to debate the Filioque against the Orthodox spokesman Nikephoros Blemmydes.
[1] In 1253, the Emperor and Manuel II sent envoys to Pope Innocent IV to more formally discuss ecclesiastical union, renewing these negotiations.
No further progress was made after 1254, however, as the architects of the entente – Pope Innovent IV, Emperor John III Doukas Vatatzes, and the Patriarch Manuel II – all died within a few months of each other, and the impetus was lost.
[2] In 1247–1248 he wrote to the Armenian Kingdom of Cilicia Hethum I and the Catholicos regarding their relations with the Byzantine Church, and in July 1250 he composed a series of responses to canonical questions.
[4] Manuel II's death is distinctly fixed as having occurred two months before that of Emperor John III Doukas Vatatzes, on 30 October 1255.