Heal Thyself

issue 04 | winter 2019
Winter 2019 – Heal Thyself

Jonathan Silverstein ‘89 keeps a framed photo on the sill of his 54th-floor window in his midtown-Manhattan office. The picture is of a woman with red hair holding an infant girl.

Silverstein is a managing partner at OrbiMed, a leading global medical investment firm with approximately $14 billion in assets and has, for the past seven years, been named to the Forbes Midas List, which annually ranks the top 100 venture capitalists in the world. He’s at the very top of his profession.

But the photo, he says, leaning over to pick it up off the sill, is a reminder of his favorite part of the job—finding cures. The child in the photo suffers from hypophosphatasia, a rare disease—estimated to impact one in every 100,000 births—which leaves sufferers unable to produce a necessary molecular building block of bones. At birth, the baby had only three bones in her hands and multiple fractures. She couldn’t lift her arms and legs and would moan constantly; there was a 75 percent chance she’d die within the first year, and even if she did survive, she would suffer a shortened life filled with crippling fractures and pain. “Many of the kids with the disease suffocate because their ribs aren’t developed enough,” says Silverstein.

But the baby survived. Treated with an experimental drug from a company called Enobia, her bone structure began to normalize. She’s now 10 years old and enjoying a normal, healthy childhood in Ireland.  

Silverstein led a major investment in Enobia, helping fund the fledgling company and later guided it as chairman of the board. “I want to be very clear: I did not develop the drug. I’m not the scientist behind it,” he says. “We visited the company in Montreal and reviewed mouse data. They had bred mice to have the same disease and then treated them with the experimental drug, and the data showed that the drug normalized their skeletal structure. We concluded that the drug had a chance to work in humans.”

Winter 2019 – Heal Thyself

Silverstein helped reshape the company, says the company’s former CEO, Robert Heft. “His impact was spectacularly successful,” says Heft, “both in terms of the quality of the company and the caliber of the impact it had on patients.”

Silverstein is still close with the family. “I saw the girl get her first dose. What a day,” he says. “That drug was a lifesaver for them.”

But now, Silverstein needs the same kind of miracle.

Diagnosed with an aggressive form of Parkinson’s in the spring of 2017, he’s putting all those things that have brought him to the top of his profession—his deep industry knowledge, his extensive network, his ability to find great ideas—to try and find a remedy that no one else has been able to find. “I’ve basically got to create a cure for myself,” he says. “I’m not counting on somebody doing it for me.”

Growing up outside of Boston, Silverstein was a rabid sports fan, frequently cheering on the Larry Bird–led Celtics at the Boston Garden. By the time he was 17, he had a defined life goal: “I wanted to be the general manager of the Celtics,” he says, smiling. “I still want that job.”

As a student, he applied for internships at every pro baseball, football, basketball, and hockey team in the country—all 130 of them. He didn’t get a single call back and wallpapered his dorm room with the rejection letters he received.

Undaunted, he enrolled in a J.D./MBA program at the University of San Diego a few years after graduation, figuring it would help in his quest to take over a pro team. As he slowly began to realize it wasn’t going to happen for him, he set his sights on what he figured was the next best thing: venture capital. “I thought venture capital was a lot like being a general manager of a team. You research companies, you invest in the ones you think have the most promise, you select your managers, and you build your team.”

But like pro sports, venture capital was a tough business to break into. He had headed to New York City after graduating from USD, and—again—no one returned his calls. It didn’t help, he says, that Denison wasn’t as widely known, and he found that the big-name banks were all looking to hire from the Ivy Leagues. “I had no chance,” he says.

His first few deals at OrbiMed were critical. “If your first three deals work out, people think you’re a hot hand,” he says.

One day, a newspaper ad caught his eye. It was a venture capital gig, but a back-office, operations-type role. Not ideal and not glamorous, but maybe enough to get his foot in the door, he figured. For 29 days in a row, Silverstein called the company’s CEO, unable to get past his secretary. On day 30, the CEO relented, and Silverstein got an interview, and soon, the job.

After a short stint there and a year and a half at a Japanese bank, he was ready to move on and weighing two offers: An investment group called Mesa Partners and upstart biotech fund, OrbiMed. Both of them were fledgling companies with a few employees that could have gone out of business, Silverstein says. He chose OrbiMed, which stayed afloat, and joined as the fifth employee. (Mesa did indeed go out of business shortly thereafter.)

Reflecting on it now, he says, his first few deals at OrbiMed were critical. “If your first three deals work out, people think you’re a hot hand, and management teams and other venture capital firms want you in their deals,” he says. And his first three deals all made a significant return, including a company called Given Imaging that made an ingestible camera, which made the firm about six times its money on the initial investment.

“I’m a very competitive person, and there’s a competition aspect to this job that I love,” he says. “I know that 50 funds in the U.S. passed on Given Imaging because they were too afraid to travel to Israel to look at the company, or they thought the market was too small. I was the only U.S. investor in the deal. The company eventually got acquired for a billion dollars.” It’s like the NBA draft, he says: He’s taking a chance on that gangly kid that everyone else is overlooking because he can see promise that no one else can—and then watching that kid become an All-Star.

Silverstein has also worked to make finance careers a reality for Denison alumni: Once he started to establish himself in the venture capital world, he started hosting a Denison intern at OrbiMed every summer, providing mentorship and valuable connections. The plan? “I wanted to improve the brand and the patina of the school,” says Silverstein. If his interns went on to successful careers at big firms, he figured, the banks would start to look beyond the Ivy Leagues and give Denison alums a chance.

Silverstein has run the program for 14 years now, and the interns have been employed by well-known investment banks like Cantor Fitzgerald, Cowen, Wedbush, Needham, Deutsche Bank, and Piper Jaffray, as well as consulting firms like McKinsey. Chad Huber ’05, a former summer intern who now works as a managing director at Piper Jaffray, was introduced to his current boss by Silverstein. “I’m forever grateful for that,” says Huber, noting that Silverstein was clear that—beyond the intro—the rest was up to Huber. “Jonathan has been an incredible friend, a mentor, and—frankly—a second father.” Cale Garverick ’13, a healthcare investment banker at San Francisco’s Cowen and Company, says the experience at OrbiMed not only opened up unimaginable career opportunities for him, but also a personal connection. “The friendship we’ve developed is incredibly valuable,” he says, noting—among other things—the Silverstein family’s attendance at his wedding.

The group of former interns has remained tight: There’s a high-stakes fantasy football league and an annual party at Silverstein’s second home on Long Island, where everyone comes—some now with families—to play pool and race in paddleboard competitions. It’s a great crew, says Silverstein. Everyone gets along, everyone tries to help each other advance in their careers. “It has worked really well, and it’s an easy thing for me to do,” says Silverstein. “It’s fun to build these friendships as I help the next generation.”

It’s part of his competitive nature, too—he wants to make sure that his Denison team has a chance to compete.

That drive has stayed constant, even as his focus has shifted. Since Silverstein began his career investing in medical devices and eventually focused on therapeutics, he’s become very adept in the field of rare disease treatments during his nearly 20 years at OrbiMed. “There’s a huge unmet medical need, and you can go very rapidly from idea to approved product,” Silverstein says. The FDA, he explains, tends to be more lenient on its development requirements for these drugs, in an effort to get them into the hands of the sickest patients quickly. “It’s probably half the time.”

And it’s all these things—his drive, his competitiveness, his ability to spot a diamond in the rough,and his vast experience and connections in the world of rare diseases—that have perfectly positioned him to find his own cure.

He gets the irony. “I feel like I’m living in a 60 Minutes story,” Silverstein says, looking out his office window. “I mean, how many people do you know that have been diagnosed with an incurable disease think they can find a solution?”

The symptoms started innocuously enough. Silverstein lost his sense of smell.  He had some dry-eye problems and got drops from his ophthalmologist. Then one day he lost his balance, fell down the stairs, and broke his kneecap. The orthopedic surgeon sewed him up but didn’t think twice about it. A few months later, he collapsed while racing his son home from the subway station, but aced a cardiovascular workup.

But in the spring of 2017, a foot tremor sent Silverstein to a movement specialist, who put all of these incidents together and suggested Silverstein get checked for Parkinson’s disease. Genetic testing confirmed the diagnosis—and determined it was a more aggressive form of the disease—Parkinson’s with a rare genetic mutation known as GBA, which affects about 10 percent of Parkinson’s sufferers.

Silverstein took a couple of weeks to process it with his wife, Natalie, and three children—now ages 17, 14, and 10. But time wasn’t a resource. Quickly, Natalie—who had spent years in the nonprofit space—helped set up The Silverstein Foundation for Parkinson’s with GBA (www.thesilversteinfoundation.org). And Silverstein hit the phones, asking his vast network of investment and research contacts to send him anything they had on Parkinson’s.

He did interviews with CNBC, MSNBC, and Forbes magazine, taking his diagnosis—and his call for help—public. “What I wanted out there was, ‘Silverstein’s sick, and he’s going to do something about it—and if you’ve got ideas, send them his way.’” Broadcasting his diagnosis wasn’t comfortable, but he knew it was necessary. “It was a weight off my shoulders. And I knew if I was going to try to solve this problem, I needed to enlist the entire planet.”

Silverstein and his wife pledged to fund the foundation with $10 million of their own money, and within months, friends, family, and a pharmaceutical company had contributed another $7 million. “I haven’t asked anybody for a penny,” says Silverstein. “So that’s been sort of overwhelming, to know that you’ve got friends and family, as well as colleagues in the industry, that care.”

And the call to arms worked, too. “I’ve gotten several hundred business plans from Taiwan to Sweden to Israel,” says Silverstein. In March 2018, The Silverstein Foundation and the Michael J. Fox Foundation  held a joint workshop on Parkinson’s with GBA. The workshop featured more than 30 disease experts from around the world. The two foundations also announced a joint research project, making $1.5 million available for GBA research.

So far, The Silverstein Foundation has funded 11 different research projects in Parkinson’s with GBA. It’s quickly established itself as a go-to source for new ideas and research—all while Silverstein still works full days at the OrbiMed office. “Nearly everyone I spoke to after I got diagnosed asked, ‘Why don’t you just retire?’” he says. “I pushed back, ‘I’m not retiring  because I’m surrounded by brilliant MDs and PhDs here, and through my work, I’m able to attract the research.’”

His hunt for a cure has already seen tangible results. The foundation has supported the development of three novel approaches to treating Parkinson’s with GBA, each of which should put an experimental drug in human clinical trials by the first half of 2019.  One of these trials is being led by Prevail Therapeutics, a company that the Foundation co-founded last summer and that has raised $75 million from the venture capital community.

“What’s encouraging about my situation, if there’s anything to be encouraged about, is that it is a genetic disease,” he says, “so we have a pretty good understanding of what’s happening.” The technology is there—science has developed great tools, and drugs can be directed in a way that previous generations could have only imagined.

In short, it makes him a bit more optimistic. He’s seen this play out before. He knows there’s a path to victory here. It’s just a matter of finding the right route.

While the hunt for a Parkinson’s with GBA treatment began with his own diagnosis, Silverstein says it’s bigger than him. “My goal is not to help just myself. My goal is to help the 150,000 people diagnosed with this disease.”

He reflects on something his father, a physician, once told him after his son’s first few deals as a healthcare venture capitalist. “I’m going to get to help thousands of people as a doctor,” his father told him. “You’re going to be able to help millions.”

It’s an ironic aspect of his work, says Silverstein—you are touching people from all over the world that you’ll never meet. But with The Silverstein Foundation, that’s changed. There was a man in St. Louis who died of Parkinson’s, and in his obituary, mourners were asked to send checks to The Silverstein Foundation. There was another donor named Mike who wrote from Ohio. He shares the Parkinson’s with GBA diagnosis and sent along $18, asking Silverstein to “get it done.”

“And if that doesn’t get you motivated,” Silverstein says, “then nothing will.”

Published December 2018
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