Adam Simon is a poster boy for the career arc that regional leaders are pinning their hopes on to generate new ventures - and eventually new jobs - as the Big Pharma workforce gets smaller.

Laid off by Merck in a global downsizing of 7,200 workers, Simon, 45, a Ph.D. physicist with serious life-science chops, crammed at two business-school boot camps - one at Penn, one at Temple - then went on to form four start-up companies.

One of them, a medical-device operation called Brain Computer Interface, is now dotting the i's and crossing the t's on a federal grant called an SBIR (Small Business Innovation Research) that seeds high-tech start-ups with money to jump-start promising new science.

That first grant, with the Army, is to explore the potential of a device that could help diagnose post-traumatic stress disorder in its earliest stages based on biological "markers" in a soldier's brain (measured noninvasively).

Early this month, BCI filed a second SBIR grant proposal - for seed money from the National Institutes of Health for a different device that would use biomarkers to catch Alzheimer's disease early, potentially before patients even showed symptoms.

The Daily News met Simon at a Bucks County Starbucks - he lives in Yardley and operates out of the Pennsylvania Biotechnology Center, in Doylestown - the day after he filed the NIH grant proposal.

Simon is known internationally for research that detects Alzheimer's biomarkers in cerebrospinal fluid, and he's a lab rat at heart. He e-mailed ahead with a strategy to help us pick him out from the morning hordes in the latte line: "I can wear plaid for both my shirt and sport coat (drives my wife nuts) and look like a scientist."

Letting go after being let go: "In my layoff, or separation, there was a designation: 25 percent upper management," Simon says. "They had cost-cutting reductions. It was a number. It had to be met.

"I was the bottom rung of upper management, leading their biomarker-discovery efforts for neuroscience.

"The day it happened, it felt horrible," he says. "I literally cried. I had seven-year relationships with people who were terminated that day.

"And then it took me about 36 hours to get over it. It was like, okay. I just started thinking about all the possibilities of where to go from there."

With a year's severance, "I had basically a year to get back on my feet - that's generous," he says. "And I have not looked back since. Whoever let me go, put my name on the list, I owe them a huge thank you. I am so much happier now."

Papa's got a brand-new bag: As a budding entrepreneur, "I quickly assessed that I was weak in business planning," he says. "So I immediately started looking around." In January 2009, he signed on for back-to-back classes in strategic business planning at Temple's Fox School of Business and Penn's Wharton Small Business Development Center across town.

"I kind of double-dipped," Simon says. "It just so happened that was Thursday at Fox from 4:30 to 6. Then I would take the train to University City and walk to Wharton," where his night-shift class ran from 6:30 to 9.

"And I had homework," he says. "My wife and kids would laugh, 'Dad's up working on some business plan for his class.'

"You've got to know what you're good at and what you're not," Simon says, "and that was extremely valuable in filling holes in my understanding of the business process."

The hardest hurdle - trust: Brain Computer Interface is one of three start-ups that Simon has launched with various business partners. The others are a biosciences effort called Neuronostics, which draws directly on his expertise in cerebrospinal fluids, and a software-privacy company called ScreenShroud.

He doesn't take a salary from any of them, so he works as a consultant to cover his household bills. (His consulting business is another start-up: AJ Simon Enterprises.)

Surprisingly, it's not the finances that have been the toughest nut to crack. "The hardest thing for me was finding good business partners," he says.

"I have a huge network of scientists, and I didn't have a whole lot of contacts in the entrepreneurial and business space. Those kinds of things don't materialize overnight, so the most important thing was remaining open, networking a lot."

The partnership courtship: Simon prefers collaborating to working alone. "It's much, much easier and much, much more effective if you've got at least two minds around the table," he says.

But it's rare to find a like-minded individual who can collaborate as a full-fledged partner and not just a service provider, he says. "And when you find people who are, you just met them two months ago. What do you know about them?

"It's not quite dating and marriage, but it's got some very long-term implications. Do you have good chemistry? That's irrational and intuitive, and there's no checklist I can provide.

"And then you do due diligence on them and they do due diligence on you."

Sometimes, the relationship just clicks. ScreenShroud had its genesis at the Wachovia Center, Simon says. "I met a guy at a hockey game in one of the lawyer booths - a sort of networking kind of thing - and he made a joke that I misinterpreted as serious.

"I kind of countered with, 'Well you could do this, and this and this. He looked at me and said, 'You're serious?'

"So, back and forth, we've now started a privacy-software company."

Other times, the interpersonal dynamics fall short. "I won't go into any detail," he says, "but I've made some mistakes along the way."

Entrepreneurial infrastructure: In addition to Wharton, Fox and the federal SBIR money, Simon has tapped into a sprawling network of E-Class supports for the life sciences in both Pennsylvania and New Jersey.

He's a big fan of BioStrategy Partners (for helping scientists learn about business), Pennsylvania Bio and BioNJ (for introductions to people of influence in their respective states), the Mid-Atlantic Capital Alliance (for building networks with investors), the Eastern Technology Council (for connecting with the life-sciences community, especially in the western suburbs) and the New Jersey Entrepreneurial Network and New Jersey Technology Council (for connecting with the Garden State crowd).

He positively gushes about Pennsylvania's Innovation Partnership, which offers "microvouchers" that scientists can redeem to pay grant writers for help with their SBIR applications.

For life-sciences incubator space, "the University City Science Center looks fantasic and the Navy Yard has superb facilities," Simon says. He chose the Doylestown biotech center as his base of operations for the shorter, more bucolic commute.

"Sitting in traffic is just a pet peeve of mine," he says. "I just want to avoid it."

Regional life sciences, a love story: Simon grew up in Maryland, earned his Ph.D. at the University of Chicago and did postdoctoral work at Princeton University and in Paris.

But it was neither the Princeton connection nor the Philadelphia region's strength in life sciences that led him to settle here.

"I fell in love in Paris with a woman who lived in Yardley, Pa.," he says. "And I got out my compass, and I drew a one-hour-drive circle around Yardley.

"This is in Paris, at the foot of the pantheon in the Jardin du Luxembourg. And I said, 'I'm going to find a job within one hour of Yardley, Pa.'

"She's now my wife. So there's a good story to that."

His E-Class story, Chapter 1: "I don't want to portray that we're farther out the gate than we are," Simon says. "It's hard work, long hours and we're only at the very beginning.

"My analogy is that getting separated out of Merck, I got thrown into the ocean, and right now I still at least have my head above water. I'm not swimming yet.

"I'm not hitting big milestones. But I am feeling like I am at least successful enough to be treading water, and I'm in the game.

"It's a long process. It's a hard process. But, for me, it's extremely satisfying."