Oral medications added

The pipeline has grown broader in recent years with the introduction of drugs that can be delivered in pills instead of by injection.

Paul Reider, vice president of chemical research, was hired away from Merck & Co. Inc. to bring that expertise once limited to pharmaceutical firms to Amgen.

His group is divided between Thousand Oaks and Cambridge, Mass., one of Amgen's research and development locations. A room near Reider's office is set up for videoconferencing and employees travel a lot between the coasts to share ideas.

After all, he said, much of discovery is serendipitous.

"We're working very hard to make sure we do not stretch the framework too much," Reider said. "We have to get big, but we have to feel small. No company has done that."

Amgen is capitalizing on the resources it has from being big while trying to avoid the pitfalls of bureaucracy that come with being a large company.

Company officials said they are most excited by the drugs Amgen has just on the horizon — drugs to treat osteoporosis or directly target cancer cells.

"I've never been, in this 18 years, as excited about what is coming out of the pipeline as I am now," said Caroline Jewitt, who oversees the production and development of the company's drugs for inflammation. "We are changing the way people think about medicine."

| Growth and criticism

Recent growth has included the acquisition of Immunex for about $17.7 billion. Amgen obtained Immunex's Enbrel, a treatment for inflammation used for rheumatoid arthritis and later approved for use against four other diseases. In 2004, Amgen acquired Tularik Inc., which provided new research capabilities and a presence in South San Francisco, a hub for small start-up biotech firms.

Amgen officials said the Immunex acquisition diversified its lineup of drugs. The company quickly made changes to increase the production of Enbrel to meet demand, something Immunex had been unable to do.

But the Immunex deal drew some heat.

Steve Silverman, who directs a private family trust with millions of dollars in Amgen stock, was one of the most vocal opponents. He said all Immunex brought to Amgen was Enbrel, calling it a "one-trick pony."

Because he does not like how the company is being run, Silverman plans to call for a "no" vote when Sharer and other directors are up for re-election on the company's board May 11 at a shareholders' meeting.

Sharer, who became CEO in 2000, has made across-the-board changes with new top management.

Some employees chafed at the changes, which created more structure and accountability, according to Amgen spokesmen. And some analysts and investors are worried the company is getting too big.

Amgen officials said the company has to stay competitive. "Growth is not an option, it's a necessity," Sharer said.

Amgen is developing into what might be called a biopharma — looking more like an established company like Pfizer, said Gary Clark, founder of biotech networking group VC Bio. They have passed the stage of exploding growth that happens with a start-up.

Biopharma is a somewhat new industry term, a hybrid of a biotech company and big pharmaceutical corporation such as Pfizer. It reported fiscal 2004 revenue of $52.5 billion — five times as much as Amgen, according to the Securities and Exchange Commission.

"Possibly the returns aren't going to continue at the same rate, but certainly they are going to be a survivor," Clark said.

Small companies have "unbounded innovation," he added, but they don't have the finances or maturity to find the right compound efficiently.

"The key to successful drug discovery is eliminating drug compounds as quickly as possible and for as little money as possible," he said.

Company has needed clout

Amgen, with market capitalization in the neighborhood of $74 billion, has the financial strength that allows the best minds to sort through the compounds efficiently.

Amgen "now has that financial war chest that makes them such a dominant player," he said.

Amgen has more than 40 research and development projects in clinical testing. But its pipeline, though broad, is immature, said Henry Dummett, senior analyst with London-based World Markets Research Centre.

It has enough promising drugs in development to ensure long-term growth, but the short term is heavily reliant on the success of AMG162, a new drug that treats osteoporosis, he said.Agreement led to problem

In 1985, to get Epogen through human trials, Amgen signed an agreement that allowed Johnson & Johnson to sell the product as Procrit for anemia not related to dialysis in the United States and most foreign countries.

In 1997, Johnson & Johnson tried to claim rights to Aranesp, a longer-lasting product based on the same gene as Epogen. Amgen won in court arbitration.

Like any large company, Amgen has faced these types of legal battles, but it has generally fared well.

The company also has not run into problems with the Food and Drug Administration on any of its approved drugs. The FDA did make the company pull ads on treating psoriasis with Enbrel, stating that the company did not do enough to show the treatment was for moderate to severe cases and carried risks.

Amgen also has dealt with the common challenge of having to yank a promising drug out of clinical trials. The company decided this past fall to stop trials of GDNF, used to treat patients with advanced Parkinson's disease, because of harmful side effects.Securing secrets

One of Pearl's jobs is to keep the 3.5 million square feet of buildings up and running.

"It's a city, when you think about 10,000 people on 150 acres of land, roughly," he said.

To keep all of those bright minds feeling safe, Amgen has a team that is a little less visible — unless someone wanders onto campus without an Amgen badge.

Every day, there are about 3,000 visitors on campus and security has to keep track of them. A visitor's badge requires a scan of the person's driver's license. After 24 hours, the badge turns red, indicating the visitor's time on campus has "expired." Most doors can be opened only with an employee ID card.

Security extends beyond an individual's movements to a strict control of information. Maps of the campus are restricted, no photos can be taken anywhere without express written approval, and a security guard, in uniform or out, is generally visible at the entrance of every building on campus.

There is concern about protecting trade secrets, ensuring the safety of employees and guarding against "certain outside groups that might not agree with what we do," Pearl said.

Amgen's success has helped the entire biotech industry grow, said Jim Greenwood, president of the Biotechnology Industry Organization, or BIO.

"Twenty-five years ago, Amgen was a biotech start-up, a fledgling pioneer in an infant industry," Greenwood said. "Ten years ago, Amgen was one of just a handful of profitable biotechs. Today, Amgen is the largest biotechnology company in the world, a leader in a $50 billion-a-year industry, and a sought-after partner for emerging biotechs."

Amgen has more than 100 partnerships and half its pipeline has come from them, said CEO Sharer.

"We must be alert to things outside of the company and be a good partner and be able to take a risk," he said. "You can't succeed in this business without casting a broad net for where innovation might reside."

The company has learned from its own experiences when it was a small company.Diversity a driving force

Amgen prides itself on diversity. Vice President for Human Resources Ted Bagley said it has been a driving force in the company's progress.

Employees with common interests have even formed groups on campus to help promote the company. Bagley was unwilling to put numbers on the company's diversity, calling it a "moving target," but he noted that the largest groups in order of size are for Asians, African-Americans and Hispanics. These and other groups such as one for women work together in shaping the company's culture, recruitment and community relations, Bagley said.

The campus is practically self-contained, with perks such as an on-campus gym that has more classes and equipment than some top health clubs, holiday package shipping at the gift shop, and a day-care center with capacity for up to 400 children.

"We try to make it as comfortable as possible for employees so they can be productive here," Bagley said. "They can stay here as long as they need to."Sought-after employer

Students at California Polytechnic University, San Luis Obispo, are always excited when Amgen comes to the annual biotechnology event, said Susan Elrod, a professor in the biological sciences department. There are students who eschew the corporate environment, but as a major employer with a good reputation, Amgen is the target for many graduates.

"They see it as a place where they might be able to grow and change and still be with the same company," she said.

Amgen is highly respected in the industry, and a leader in the development of therapeutics, Elrod said. It dwarfs most companies with the number of drugs on the market.

"One is a huge number, to have eight is amazing," she said. "Small companies are banking on one product."

On Fortune magazine's list of 100 Best Companies to Work For, Amgen has settled into spot No. 33 for the past two years.

The magazine cited the "fabulous" 401(k) retirement plan as a main factor. The company contributes 5 percent of a full-time employee's salary to the plan, as well as matches an employee's contribution up to another 5 percent. The benefit begins on the first day of employment.

Fortune reported that the most common salaried job at Amgen is a sales representative earning $137,490 per year, and the most common hourly job is a research assistant II, averaging $76,844 per year. The company reports annual turnover is about 5.5 percent.Dishwasher became millionaire

Other employees have also done well. The company's first dishwasher, who is now head of landscaping, is a millionaire. When he happens to see her on the campus, Fenton asks her what she's still doing at Amgen. "She asks me the same thing," he said.

"There are a number of us 'volunteers,' " he said. "We come to work not so much for the salary but for the gratification of working in an organization that really does help people."

As the company ballooned, the challenge became how to retain the sense of community and core values established as a start-up.

Fenton calls it an "informal, intense place."

It seems no employee ever wears a tie. And even CEO Sharer wore a dark-blue pullover sweater over an open-collared shirt when interviewed by The Star.

Pearl said the company still has teams of employees make decisions.

"Decisions get made and executives, I think, sometimes are a servant to make sure those decisions get carried out rather than someone who tries to get in the way of that decision," he said.

But there are the hallmarks of a big corporation. Steering everyone in the same direction is more difficult than it was when then-CEO Rathmann poured Pearl a cup of coffee one morning just because they were in the same building.

With such bulk, the worry is that the company will lose its nimbleness. It goes back to the motto: think big, act small.

Pearl said the opportunities afforded within a company come from growth. Young scientists coming out of graduate school see opportunities and comforts of working for a large corporation.

"They should dream of Amgen," he said.

A corner in the fourth deck of the campus parking structure tells what kind of rewards are lined up: Lexus, Mercedes, BMW, BMW Coupe. There, on the backside of cars, are emblems of financial comforts.

The human resources department gets thousands of resumes every day. Three hundred will make it to a staffing manager handling 40 job openings at a time.First success

The company became more focused with the discovery of its first marketable drug. Scientist Fu-Kuen Lin successfully cloned a gene in 1983 that would lead to the anemia treatment Epogen, which became a bigger success than company officials had imagined.

Amgen sells Epogen to treat anemia in patients undergoing dialysis and licensed the product to other companies to sell for treatment of anemia caused by other things, such as chemotherapy.

The initial discovery was followed a few years later by another breakthrough with Neupogen, a drug used to help prevent infections in patients undergoing chemotherapy. Amgen now has five blockbusters, an industry term for drugs that generate sales of more than $1 billion a year.

Amgen's initial public stock offering occurred in 1983, a few months before the Epogen breakthrough. Though offered at $18 a share, the stock closed at $16.75 a share the first day.

Through several stock splits over the years, one share has multiplied to 48. One share purchased for $16.75 that day would be worth about $2,784 today.

Fenton has the IPO certificate hanging over his desk, a reminder that he could have stopped working years ago. In 2004 alone, he received an annual salary of $767,755, plus a $1.21 million bonus.In the beginning

Company founder Bill Bowes, a venture capitalist, first hatched the idea that would lead to Amgen in 1979 after seeing the success of future competitor Genentech, a South San Francisco biotech firm founded in 1976, according to Amgen's records.

Bowes and a few other venture capitalists created a scientific advisory board and incorporated Applied Molecular Genetics on April 8, 1980. After starting the company, Bowes formed U.S. Venture Partners, which later helped establish companies such as Sun Microsystems and Applied Biosystems, according to Amgen's records.

There wasn't much science that went into selecting Amgen's location.

Some members of the scientific advisory board were located at California Institute of Technology in Pasadena; University of California, Santa Barbara; and University of California, Los Angeles. Thousand Oaks was right in the middle, Fenton said. And housing was inexpensive in the area at the time.

In the 1980s, Wayne Pearl moved to the city for the sunshine.

"If Amgen had been in Chicago, I don't know if I would have come to Amgen," Pearl said. "Amgen in Southern California was a dream come true, at least for a New Jersey guy."

Since joining the company, Pearl has been tapped over and over again for new assignments. He never thought of leaving because he was never bored.

"It must have been 17, 18 years ago, my boss, Dennis Fenton, came up to me one day and said, 'Wayne, we would like you to design a plant.' I said, 'I've never designed a plant before,' and he said, 'Neither have I.' "

As vice president of Thousand Oaks operations, Pearl now manages the plants he designed.

The biggest challenge early on was making Amgen a viable company. No one knew how recombinant DNA technology would translate into a business, Fenton said.

In addition to looking for human drugs, the company was researching diagnostics, animal growth hormones and extraction of oil from shale — anything that might be profitable.

"The thought was some of the other things might generate revenue faster," Fenton said.After reporting revenue of $10.6 billion in 2004, a 26 percent gain from the previous year, Amgen is forecasting a more conservative outlook this year with growth from the single digits to low teens.

The projection is a little troubling to some shareholders and Wall Street analysts, who have come to expect annual revenue growth in the 20 percent range.

Still, Amgen, now driven by board Chairman, CEO and President Kevin Sharer, is committed to going its own way.

Some worry the company has become too large and too beholden to investors to continue going after the long shots that marked its early discoveries. But company officials maintain the next 25 years will be marked by the same values, work ethic and commitment to patients that drove it as a start-up.promise of success and Southern California sunshine, Fenton ended up accepting a job as a research scientist, becoming one of the first 15 employees.

Today, the company is called Amgen Inc., the world's largest biotech firm in terms of revenue, with eight drugs on the market and a pipeline of 40 compounds being tested as possible new treatments.

Fenton, now executive vice president of operations, can view the company's sprawling campus through his fifth-floor office window. There are 44 buildings and about 6,600 employees at the Thousand Oaks headquarters, with another 7,800 workers at company operations in several other U.S. cities and abroad.

On Friday, Amgen will mark its 25th anniversary since founder Bill Bowes teamed with a few other venture capitalists to form the company. Despite its tremendous growth, Amgen aspires to "think big, act small."Dennis Fenton remembers arriving in Thousand Oaks more than 20 years ago to interview for a job with a small start-up firm called Applied Molecular Genetics.

The company shared a small building with a ball-bearing manufacturer and a choral group. Fenton was greeted by a secretary and then-CEO George Rathmann.

Rathmann promised him the company would one day be bigger and better than pharmaceutical giant Pfizer Inc. — Fenton's employer. Lured by the