The dramatic gains marked an inflection point in Syria’s nearly 6-year-old conflict, threatening to dislodge armed opponents of Assad from their last major urban stronghold.

Syrian government forces captured more than a third of opposition-held eastern Aleppo on Monday, touching off a wave of panic and flight from the besieged enclave as rebel defenses in the country’s largest city rapidly collapsed.

The dramatic gains marked an inflection point in Syria’s nearly 6-year-old conflict, threatening to dislodge armed opponents of President Bashar Assad from their last major urban stronghold.

Reclaiming all of Aleppo, Syria’s former commercial capital, would be the biggest prize of the war for Assad. It would put his forces in control of the country’s four largest cities as well as the coastal region, and cap a year of steady government advances.

It also would bolster his position and momentum just as a new US administration is taking hold, freeing thousands of his troops and allied militiamen to move on to other battles around the country.

Charles Lister, a senior fellow at the Washington-based Middle East Institute, said the opposition’s losses in Aleppo are the biggest since 2012.

“Aleppo city itself has also been a consistent base of moderate opposition activity, so its collapse spells what could be an existential blow to the moderate opposition from which it’ll likely struggle to recover,” he said.

Ever since it joined the uprising four years ago, eastern Aleppo tried to make itself a model for a Syria without Assad. It elected local leaders, ran its own education system and built an economy trading with the rebel-held countryside and neighboring Turkey.

Its residents kept life going amid ferocious fighting with the pro-government western districts, but four years of battles and airstrikes have reduced entire blocks in the territory to rubble.

Helped by massive Russian air power and thousands of Iranian-backed Shiite militia fighters from Lebanon, Iraq and Iran, Assad renewed his push for Aleppo this month. The besieged eastern districts came under intense airstrikes that killed hundreds in the past two weeks.

More than 250,000 people are believed trapped there with limited access to food, water and medical supplies. They include more than 100,000 children, the UN says.

“It is stinging cold, food is scarce and people are shaken in the streets,” Mohammad Zein Khandaqani, a member of the Medical Council in Aleppo, told The Associated Press in a text message from eastern Aleppo.

Some are taking refuge in mosques while others moved to homes of displaced people in safer areas, he added.

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