Senate Republican leaders are struggling to win support from holdouts in their party for what may be their last chance for a long time to pass a GOP-only repeal of Obamacare.

Sen. Susan Collins of Maine said Friday she’s leaning against the bill because among other things it undermines protection for people with pre-existing medical conditions. “The premiums would be so high they would be unaffordable,” she said.The Senate needs to act by Sept. 30 to use a fast-track procedure to keep Democrats from blocking the proposal by Republicans Lindsey Graham of South Carolina and Bill Cassidy of Louisiana. But a cluster of GOP senators haven’t committed to the bill, which would send federal Obamacare money to the states in block grants to create their own health programs, cut funding to most states, and potentially let insurers charge sick people more.

Republicans control the Senate 52-48, meaning they can afford to lose no more than two votes among the following senators who stand out as the most likely to defy party leaders. They include the three who killed Majority Leader Mitch McConnell’s health plan in July — Susan Collins of Maine, Lisa Murkowski of Alaska and John McCain of Arizona. The fourth, Rand Paul of Kentucky, says he’s a “no” vote and won’t change his mind.

President Donald Trump warned on Twitter on Friday, “Rand Paul, or whoever votes against Hcare Bill, will forever (future political campaigns) be known as ‘the Republican who saved ObamaCare.'” The president is working the phone on the issue and is “open to having face-to-face meetings,” adviser Kellyanne Conway said on Fox News. “The president is leaning in all the way.”

The Brookings Institution estimated Friday that the Graham-Cassidy plan would reduce the number of people with health coverage by about 21 million a year from 2020 through 2026. The number may be larger, it said, because of difficulties in setting up state health systems by 2020 and possible market turmoil in the final years. “What is clear, however, is that the legislation would result in very large reductions in insurance coverage,” Brookings said.

The Center on Budget and Policy Priorities said Medicaid funding cuts would equal 16 percent of projected state budgets in 2027. “That’s more than what states provide for higher education,” it said.

Susan Collins

A leader of GOP moderates, Collins’s stated concerns about the Graham-Cassidy plan are similar to those she had about McConnell’s earlier proposal: She is alarmed at the possible effect of cuts to Medicaid and the potential impact on the chronically ill. This week, she voiced concern that the measure doesn’t continue Obamacare’s protection against higher insurance rates for people with pre-existing medical conditions — even though the bill’s sponsors say they would still be shielded.

Maine could lose $1 billion over 10 years under the new health measure, Collins said she learned from the state hospital association. Changes of that magnitude are being proposed while “short-circuiting the process” by not waiting for a full Congressional Budget Office analysis of the plan’s likely effects, she said.

There has been little sign of an effort by party leaders to win her vote. Senate Finance Committee Chairman Orrin Hatch said in an interview Thursday that many in the party view Maine, which has an aging population and struggling rural hospitals, as having unique challenges.

Lisa Murkowski

The Alaskan is probably the most independent-minded Senate Republican, winning re-election in 2010 as a write-in candidate against a Tea Party challenger who beat her in the GOP primary. Her state has its own difficulties — it’s a vast, low-density place with the nation’s highest health-care costs.

Murkowski opposed the McConnell bill because she said her constituents would be hurt by Medicaid cuts and high premiums in the individual market. She hasn’t announced her position on the Graham-Cassidy measure, saying she’s still studying it.

The lobbying for Murkowski’s vote is the most intense among all the holdouts. After Graham and Cassidy met with McConnell Wednesday to discuss plans for a floor vote, they moved quickly into discussions with Murkowski and Alaska’s other senator, Republican Dan Sullivan. Graham said backers of his bill are well aware the state has added challenges, and talks appear to be continuing on Medicaid provisions that might lure her support. Yet in July, a special Alaska provision wasn’t enough to snag it.

John McCain:

McCain cast a surprise vote against McConnell’s bill when he returned to Washington in July after a brain-cancer diagnosis. He lambasted the final proposal and faulted the partisan process of writing and voting on the bill while bypassing the “regular order” of committee hearings and debate.

This time, Republican leaders are trying to assuage him with a single hearing before the Senate Finance Committee on Monday. Yet there’s no plan for a committee vote, and the Sept. 30 deadline means there won’t be a full CBO analysis of the plan’s effect on health coverage and costs.

Republican leaders are banking on a personal connection to change McCain’s mind. He is Graham’s best friend, and the South Carolina Republican is leaning hard on his chum to back the health proposal. Arizona Governor Doug Ducey, a Republican, has also endorsed the bill.

McCain hasn’t said publicly how he’ll vote, though he complained again about the speedy process.

“Regular order is about having legislation, having hearings, having debate, having amendments, turning out a product,” he told reporters Tuesday.

Rand Paul

The small-government conservative from Kentucky says he is a hard “no” vote against the Graham-Cassidy bill. The notion of more flexibility for states doesn’t mask the massive government spending, he says, and it avoids what he really wants to do: repeal Obamacare altogether.

“It’s another incarnation of replace” instead of a repeal of the Affordable Care Act, he told reporters this week. “I won’t support it.”

He insisted Wednesday there’s no way he’ll change his mind. Still, he’s from McConnell’s home state of Kentucky and he voted in July for the party leader’s bill, so leaders are holding out hope that if Paul’s vote is needed, he’ll have a change of heart.

Some additional Senate Republicans haven’t committed to vote for the Graham-Cassidy bill, though they supported the McConnell measure in July. They include Rob Portman of Ohio and Shelley Moore Capito of West Virginia, from states that took advantage of Obamacare’s Medicaid expansion, as well as conservative Ted Cruz, the Tea Party Texan who continues to press for looser rules for insurers.