A day after clashing with Russian President Vladimir Putin over how to handle the crisis in Syria, Obama hosted a counter-terrorism summit at the United Nations to take stock of the one-year air war against IS fighters in Iraq and Syria.
"In Syria (...) defeating ISIL requires, I believe, a new leader," Obama told the gathering of some 100 leaders, held on the sidelines of the UN General Assembly.
Assad's fate is the key bone of contention between Washington and the Syrian leader's Russian and Iranian allies amid intense diplomacy over the way forward to end the four-year war that has killed more than 240,000 people.
At the summit, Obama said the United States was ready to work with Russia and Iran to "find a political mechanism in which it is possible to begin a transition process."
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The United States has long insisted that Assad must leave power, but Obama did not specify in his remarks whether the Syrian leader could take part in a transition in an interim role.
Russia is to host a special UN Security Council meeting tomorrow on the same issue -- an event bound to highlight sharp differences in approach.
French Foreign Minister Laurent Fabius accused Russia of displaying bravado on the Syria crisis that had yet to be backed up with action against the IS group.
"You have to look at who is doing what. The international community is striking Daesh. France is striking Daesh. The Russians, for the time being, are not at all," Fabius told a news conference, using the Arabic acronym for IS.
The counter-terrorism summit takes place a year after Obama stole the limelight at the last UN gathering when he vowed to crush IS and called on countries to join the United States in the campaign.