Detroit - The scientist widely credited with co-discovering the best-selling drug in U.S. history - cholesterol-lowering Lipitor - is quietly back at it.

After reviving Esperion Therapeutics in 2008 - just a year after Pfizer had closed the first version of the biotech company - Roger Newton is once again taking aim at cholesterol.

This time he's taking a different approach: Seeking to create a drug that reduces so-called bad LDL cholesterol in people whose bodies don't respond well to statins.

The irony is not lost on biotech industry observers. Where Lipitor, his first creation, falls short, Newton now sees a huge opportunity.

"Roger is the quintessential entrepreneur and innovator in the heart disease space," said Stephen Rapundalo, CEO of MichBio, Michigan's life sciences association. "You can't beat his credentials in terms of being the father of Lipitor. His commitment to finding treatments for patients is second to none."

But before he could target a drug at patients who have poor tolerance for statins, which help inhibit an enzyme that fosters the buildup of cholesterol, Newton had to first identify the market opportunity.

Only within the last several years have scientists recognized that about 1 in 5 patients are affected by statin intolerance, which often manifests itself as muscle pain or weakness.

"When Lipitor first came out, there was no real knowledge of this," Newton said.

A few months after Newton handed off the CEO reins to his executive partner in the first Esperion, Tim Mayleben, the company filed for an initial public offering and went public on the Nasdaq stock exchange in June 2013.

Since then, the stock has more than quadrupled from its IPO price of $14. Shares hovered around $64 on Monday of last week.

Investors seem to believe that Newton may have discovered the elusive formula to help fight cholesterol without using statins.

"It was not obvious to anybody except perhaps to Roger that the world needed another small-molecule LDL-lowering drug," Mayleben said. "It turns out this is a target that nobody in the world knows better than Roger does."

In November, Esperion reported positive results from a Phase 2 clinical study for its primary drug, called ETC-1002. By the end of 2015, the company expects to begin Phase 3 trials - the final phase of testing required by the U.S. Food and Drug Administration - to determine the drug's safety and efficacy before asking regulators to approve the drug for sale.

Mayleben said Esperion's target is to put the oral pill on the market by 2018 or 2019.

"It has the potential to be a multibillion-dollar drug," he said. "We're not shy about saying that."

It would be the second global megahit for Newton, who helped invent Lipitor as a scientist for Parke-Davis, which was later acquired by Warner-Lambert.

After hitting the market in 1997, the drug's sales topped more than $125 billion in its first 15 years. It was a profit giant for global pharmaceutical firm Pfizer, which had acquired the drug when it bought Warner-Lambert in 2000, before its patent expired in 2011.

Newton cemented his status as a rock star in the biotech world by launching the first version of Esperion in 1998 and selling it to Pfizer for $1.3 billion in 2004.

Then, in a shocking move, Pfizer shuttered its entire Ann Arbor campus in 2007, including the Esperion division. The company offloaded the Esperion unit's intellectual property to Newton in exchange for equity in his new company and today Pfizer retains a 4.5 percent stake in the firm.

Newton restarted Esperion in 2008, securing venture capital investors amid the global financial crisis and arranging a deal to transform the division's old R&D laboratory into a biotech incubator.

In the biotech world, it typically takes about a decade to incubate a new drug and bring it to the market, a tremendously difficult feat amid enormous regulatory scrutiny, a stiff fundraising environment and a saturated market for drugs.

But investors have given Esperion the cash it needs. After raising $91.6 million through a sale of shares to investors in October, the company ended the year with about $140 million in cash.

Mayleben said that's enough cash for the company to launch and finish its Phase 3 trials without raising another dime.

The company has taken a disciplined approach to growth. The first Esperion grew too quickly and had to lay off employees after 9/11 in what Newton has described as one of the most difficult moments of his professional career.

This time around, Esperion is operating with a smaller workforce of 21 employees, a figure that will grow gradually as Phase 3 trials begin. The company is relying heavily on consultants specializing in clinical services to conduct some of its work.

That partially reflects the experience gleaned by the company's employees, about 70 percent of whom worked in the original Esperion.

"It's a different global economy and we've been very disciplined," Newton said. "I promised myself we'd never go through what we went through."

Esperion leases lab space at the Michigan Life Science and Innovation Center, a 57,000-square-foot facility that once housed the original Esperion and is now an incubator run by the Michigan Economic Development Corp. Esperion's corporate headquarters is south of Ann Arbor.

As the company continues making clinical progress, it has received considerable "inbound interest" from prospective pharmaceutical partners, Mayleben said.

But he said the company is keeping its options open. An acquisition is possible at some point, or the company could continue to develop the drug and build its own sales force when it hits the market. It's unlikely that the company would have a huge local presence.

"Their success is significant because they've always been the poster child for Michigan's entrepreneurial community in the biosciences," MichBio's Rapundalo said. "They've had a first round of success - huge success - that really put Michigan on the map. And here they are doing it all over again, albeit in a somewhat different manner in a far more challenging environment, and succeeding once again. Whether the ultimate payoff will be similar, time will tell."

ESPERION THERAPEUTICS

Corporate headquarters: Ann Arbor, Mich., area

CEO: Tim Mayleben

Founder: Roger Newton, coinventor of Lipitor, the best-selling drug in the U.S.

Technology: Esperion is developing a pill that would help lower bad LDL cholesterol in the 20 percent of patients whose bodies don't respond well to statins such as Lipitor.

Redux: Newton founded the first company called Esperion Therapeutics in 1998 and sold it to Pfizer for $1.3 billion in 2004. Pfizer closed the company in 2007 and sold the intellectual property to Newton, who restarted the company in 2008.

IPO: Went public in June 2013