The tale of the company’s triumph from that near-death experience is a stunning example of the biotech industry, where noble pursuits to cure diseases collide with financial pressures to strike it rich — and only a fraction of a fraction ever succeed.

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SUNNYVALE, Calif. — Biotech company Pharmacyclics was teetering toward bankruptcy. Its one big product had flopped. Its top chemist, co-founders and entire board resigned, frustrated and disappointed. Its new CEO knew almost nothing about biotech. And then the recession hit.

All it had left was a single chemical, bought for cheap because no one else wanted it.

The tale of the company’s triumph from that near-death experience is a stunning example of the biotech industry, where noble pursuits to cure diseases collide with financial pressures to strike it rich — and only a fraction of a fraction ever succeed.

Inside Pharmacyclics

Pharmacyclics was built by three men personally touched by cancer, but only one was around when the company’s dream was finally realized.

Jonathan Sessler

The Stanford grad student’s cancer prompted him to use his chemistry knowledge to fight the disease while at the University of Texas. The Pharmacyclics co-founder never worked at the company day to day, instead remaining at the Austin-based university.

“One of the things you learn fighting cancer is never give up. If something’s important, you keep fighting,” Sessler said. “This is a company that kept fighting.”

Dr. Richard Miller

Miller was Sessler’s doctor at Stanford, and Pharmacyclics was another in a series of venture-funded biotech startups for the scientist.

Miller first helped found IDEC Pharmaceuticals, which received funding from Kleiner Perkins and was acquired in 2003 for $6.8 billion. Pharmacyclics also received funding from Kleiner Perkins.

Miller has recruited many of the scientists who developed Imbruvica at Celera Genomics and Pharmacyclics for a startup named Corvus Pharmaceuticals. Miller raised $33.5 million in Series A venture funding for the company, led by OrbiMed Advisers.

Bob Duggan

Duggan, who grew up in San Jose, Calif., launched an early Ethernet company and sold it for about $50 million, then helped build Computer Motion, an early surgical-robotics company.

Sunnyvale-based Intuitive Surgical merged with that company in 2003, with Computer Motion receiving one-third of the stock in Intuitive Surgical. Duggan — whose son died of brain cancer — then invested in Pharmacyclics, partly to protect his investment in Intuitive Surgical.

“Biotech was the one thing that could threaten my large asset, Intuitive Surgical, because with biotechnology you may prevent the disease from ever happening or cure it before surgery,” he explained.

Duggan stepped down from his CEO role after the merger with AbbVie was complete.

“We created a legacy,” Duggan said.

Pharmacyclics’ little-known chemical, now a drug called Imbruvica, sent company shares soaring from $2 to $261.25 in one of the largest acquisitions in Silicon Valley history, when pharma giant Abb­Vie bought the Sunnyvale, Calif., firm for $21 billion in 2015.

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Even more profoundly, the drug that saved Pharmacyclics also is aiding once-desperate patients, helping to achieve the founders’ original goal: beating back cancer.

“One of the things you learn fighting cancer is never give up,” said co-founder Jonathan Sessler, a cancer survivor himself. “This is a company that kept fighting.”

Sessler and co-founder Richard Miller did not have grandiose dreams of a billion-dollar biotechnology company when they first met at Stanford University in the late 1970s. They just wanted Sessler to survive.

While studying for a graduate degree in chemistry, Sessler had suffered a relapse of Hodgkin’s disease, a type of lymphoma.

Miller was an oncologist and researcher at Stanford who already was a highly regarded entrepreneur after helping to found the successful San Diego-based IDEC Pharmaceuticals, maker of the billion-dollar drug Rituxan for treating non-Hodgkin’s lymphoma.

Together, they helped Sessler defeat cancer — and wanted to help others, finding molecules that could be turned into new therapeutic drugs.

In 1991, the two men co-founded Pharmacyclics, with financing from Kleiner Perkins. An initial public offering in 1995 brought in more than $25 million, money that helped fund drug development over the next decade.

They pinned their hopes on a drug called Xcytrin, which showed promise in disrupting cancer cells, keeping them from spreading to the brain and making them more sensitive to radiation. The market is large: An estimated half of the 1.3 million people diagnosed with cancer every year are treated with radiation.

To conduct major trials to earn federal Food and Drug Administration approval, Pharmacyclics needed more cash.

Bob Duggan arrived as a major new investor.

An astute businessman who knew nothing about drug-hunting, Duggan had been looking for a new project in 2004 with his windfall from the merger of his surgical-robots company, Computer Motion, to Intuitive Surgical. Like Miller and Sessler, he had a personal interest, witnessing his son’s lost battle against brain cancer.

“I thought, ‘If there’s ever something I can do in that area that would make a difference … ’” Duggan said.

But it soon became clear that Xcytrin wasn’t going to make that difference. As Duggan built his stake in the company and pushed for the drug to be tested on solid tumors, Xcytrin kept getting denied by the FDA. Meanwhile, other approaches from competitors caught and surpassed it.

While the final set of trials showed that patients receiving Xcytrin along with radiation lived longer than those who did not, the few months it gave was deemed statistically insignificant by the FDA.

Frustrated and disappointed, the men conceded by late 2007 that Xcytrin would never measure up.

“We worked it up as completely and thoroughly as you possibly could, but bottom line, it didn’t work well enough,” Miller said. “I knew that dog wouldn’t hunt.”

That’s a common fate for chemicals, no matter how promising. Only 12 percent of drug candidates that enter clinical testing are eventually approved for patient use, according to Andrew Powaleny of the Pharmaceutical Research and Manufacturers of America.

On average, it takes at least 10 years and more than $2.6 billion to bring a chemical from the research pipeline to patients.

Wall Street sent shares in Pharmacyclics plummeting to $2. Then, when it seemed things couldn’t possibly get worse, the recession hit, jeopardizing the chances for new investment.

Duggan, by then a director, decided to exercise a tender offer that pushed his stake to nearly a quarter of the company, and he took the reins as CEO.

With tensions growing, Miller left the company with more than 1.5 million stock options and a one-year severance package, including his $438,000 salary. Then he went to start another biotech company.

Sessler went, too. So did the entire board of directors, en masse. “I didn’t want to stay in that environment,” Miller said.

But he left behind a gift — one of the most lucrative Plan B’s in Silicon Valley history.

In 2006, as hopes for Xcytrin were fading, Miller got a tip that Celera Genomics was looking to sell off some molecules in its research pipeline. He visited the company, famed for its role in sequencing the human genome, to talk about purchasing a few.

One particular chemical caught his eye.

“They sort of glossed over it,” Miller recalled. “But I knew from my background that it was potentially very important.”

While Miller saw promise, Celera saw problems. The chemical inhibits a protein called Bruton’s tyrosine kinase — essential to immune system B cells. So it seemed likely to do more harm than good.

In animal trials, it had been lackluster. While most drugs pass through the system, this chemical is known as “covalent.” It forges a lasting bond and shuts down the protein permanently.

The pharma industry traditionally has steered clear of covalent chemicals, said Lee Greenberger, chief scientific officer of the Leukemia & Lymphoma Society. “It is tried with great trepidation.”

But Miller, an expert in blood cancers, knew something Celera didn’t: In B-cell cancers, this protein is hyperactive — and by inhibiting it, cancer progression might be delayed. And the chemical doesn’t completely knock out the protein, so normal B cells can survive, Greenberger said.

The chemical had been discovered decades earlier, through lab work funded by the society, Greenberger said. But it had languished because its target — the B-cell protein — wasn’t thought to be a big driver of disease.

Miller worked out a deal to buy several of Celera’s pipeline candidates, including this B-cell prospect, for a cost of about $6 million, with $2 million in cash.

Then he recruited about a half-dozen Celera scientists to improve the chemical and better understand its mechanism.

“It was a sleeper,” its potential unrecognized, Greenberger said.

Many drugs are abandoned or forgotten in the pipeline of pharma companies — never reaching patients.

Lipitor, a cholesterol reducer, nearly died at birth. After animal tests showed no benefit over an existing drug, and no process for scaled-up production, maker Warner-Lambert agreed to fund only one human trial. Lipitor went on to become the world’s first $10 billion-a-year drug.

Financial life support

Duggan spent $6 million of his own money to keep Pharmacyclics on life support and get the chemical into human testing.

In 2013, Imbruvica was approved for treatment of chronic lymphocytic leukemia and was later cleared for treatment of other types of cancers. It has been tested on more than 6,000 patients, with more tests under way for a range of other cancers and even solid tumors, Duggan’s original goal.

Annual sales are expected to hit $5 billion; if it earns approval for other types of cancer, sales could reach $7 billion a year.

While Imbruvica doesn’t cure cancer, if taken daily it controls the disease for two to three years, extending the lives of terminal patients. It’s the best hope for those who have failed conventional treatment, or people whose genetics mean they aren’t helped by existing drugs. And it doesn’t suppress production of normal cells.

The first drug of its type to enlist this internal cell-killing approach, it has opened up a whole new area of research. Even after the primary patent expires in 2026, it will be remembered for opening up a broad therapeutic vistas.

“It has a real impact,” Greenberger said. “The company was brave enough to put it in clinical trials and stick with it.”

Company reborn

A phoenix rising from the ashes, Pharmacyclics’ staff swelled to 500. Its sales — and company revenues — skyrocketed. A single pill costs $90, working out to $98,550 to $131,400 per patient every year, depending on the diagnosis. Patients must take it for the rest of their lives, guaranteeing steady demand.

Company revenues more than tripled in 2013 and rose another 180 percent in 2014 to $730 million.

Then, pharmaceutical giants came calling. A bidding war broke out for the Sunnyvale company, and North Chicago, Ill.-based AbbVie won in May with an astounding offer of $261.25 per share, for a total of roughly $21 billion. AbbVie said it expects Imbruvica’s annual sales to reach $5 billion. The acquisition ranks as one of the top 20 pharma deals in history.

Only two Silicon Valley acquisitions involving a company came with a richer price tag, without adjusting for inflation: Genentech, the region’s first biotech effort, was taken over by Roche for $44 billion in 2008, and Hewlett-Packard bought Compaq for more than $25 billion in 2001.

The two men behind the chemical, now estranged, cherish the roles they both played in its unlikely birth.

“The drug is working,” said Duggan, whose stake in the company became a $3 billion fortune. “We had the courage to work the drug and to spend the money necessary to keep trying.”

Miller now uses the drug to treat his cancer patients.

“I am using a drug I helped develop,” he said. “That is very gratifying.”