In the wake of the stunning by-election win in Chesham and Amersham, the Lib Dem leader will ignore lowly poll ratings to insist his party holds the key to the next general election result.
Sir Ed will also call for more help for carers, parents, and small businesses, when he makes his first speech in front of a live audience since winning the leadership 13 months ago.
And he will demand tougher UK leadership on the climate emergency, with a ban on new oil, gas and coal companies from the London Stock Exchange.
The mainly online conference has also called for a five-point “Health Data Charter”, to set out key tests for whether data sharing is in the interest of the public and the NHS.
And it has demanded both sanctions and a Winter Olympics boycott on China over its treatment of the Uyghur minority, widely condemned as genocide.
In June, the Lib Dems dealt Boris Johnson a severe blow when they overturned a 16,000 majority in true-blue Chesham and Amersham – raising questions about the foundations of his “blue wall”.
“Make no mistake: the electoral arithmetic is clear. These Conservatives can’t be defeated next time unless we Liberal Democrats win Tory seats,” Sir Ed will tell a 100-strong gathering in London.
“Boris Johnson will stay in Downing Street unless we throw him out. It’s why our victory in Chesham and Amersham was so important.
“We showed – against all the odds – that even in deepest, bluest Buckinghamshire the Tories can be beaten. And we showed Liberal Democrats are the ones to do it.”
On climate action, the leader will say: “The UK should be leading the world on climate action, with a radical new approach.
“To move trillions of dollars, yen, euros and pounds out of fossil fuels and into renewables. By properly holding to account the powerful fossil fuel firms and the powerful in the City of London.
“Banning new oil, gas and coal companies from the London Stock Exchange. Stopping the flow of money from your pension funds into the dirty industries of the past.
“As we host the global climate talks in Glasgow, we should stop London hosting the world’s fossil fuel investments.”
Sir Ed is using the conference to underline his anti-Tory stance, vowing to never help to put Mr Johnson back into No 10.
He has also ruled out a formal alliance with Labour or the Green party, but the traditional policy of equidistance between the big two parties is effectively over.
The leader said he was “genuinely staggered by how many people said that they won’t vote Conservative until Johnson goes”, on doorsteps in Chesham and Amersham.
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