When Craig Crews was growing up in Virginia, his father worked for NASA. And while that might sound exciting to most of us, young Craig wasn’t impressed.
“He was a researcher doing very basic things,” Crews recalls. “He was looking at the strength of different wing materials. It’s called fatigue and fracture. He would just simply bend things until they snapped.”
The fundamentals of materials science seemed tedious, theoretical and lab-bound.
“I thought it was the most boring thing ever,” Crews said.
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That all changed in 1979, when a McDonnell Douglas-made DC-10 jet taking off from Chicago’s O’Hare Airport suffered a catastrophic failure. A strut supporting the left engine cracked and fell off, causing the plane to crash just a mile from the end of the runway.
All 258 passengers and 13 crew on board were killed. It remains the deadliest aviation accident on U.S. soil.
“My father, being the world’s expert in fatigue and fracture of airplane materials, was called in to McDonnell Douglas, and he stayed there for months trying to figure out what was wrong,” said Crews.
“That was, for me, a really important moment where I realized one could be passionate about pure, curiosity-driven, basic science — but also have an applied bent to it.”
Crews himself was not destined for materials science but the interface of chemistry and biology. In uniting the two disciplines, he has carved out a stellar academic career, from undergraduate work at the University of Virginia, to a Ph.D. at Harvard, and now 28 years and counting at Yale, where he is the John C. Malone Professor of Molecular, Cellular and Developmental Biology.
He’s also the executive director of the Yale Center for Molecular Discovery.
And that excitement to see the impact of theoretical science in the real world, first ignited during his youth, has driven him to launch four successful biotech startup companies, one of which, New Haven-based Arvinas, now employs 450 people and has a market capitalization of more than $1 billion.
“They now have three drug candidates that are in clinical trials for breast and prostate cancer,” said Crews. “And it’s really fun that some of those trials are actually done here at Yale. It’s a nice, circular story.”
Collaboration drives innovation
Crews’ academic training seesawed back and forth between biology and chemistry. He completed his undergraduate degree in the chemistry department at the University of Virginia.
“Then, they did not have a biochemistry department,” he says, “and so I was always exploring the biological side of the chemistry department.”
After that, during a year in Germany at the University of Tübingen, “I just went full bore into biology, which was quite an eye-opener,” he says. Putting his chemical training in service of answering biological questions, “I was able to do biology that biologists could not do.”
It convinced him that his graduate degree, at Harvard, should be in biochemistry.
The interplay between the two disciplines fundamentally shapes the way he thinks about innovation.
“It’s hard to be innovative as a team of one, because it requires a diversity of thought, diversity of experience, diversity of skill set,” he explains. “That is reflected in my laboratory where I have half chemists, half biologists.”
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The tension and collaboration between chemistry and biology also sparked a realization about an interface between two other worlds — academia and business.
“That led me to this idea that what we’re doing in my academic lab could have real-world applications in terms of drug development,” he said. “Can we go one step further with my academic chemical tools in the private sector?”
Billion-dollar molecule
He had a model from his early career, when he worked in the lab of Dr. Stuart Schreiber, a pioneer of chemical biology, and an integral figure in the founding of Vertex Pharmaceuticals.
Vertex’s story was documented by Barry Werth in the book, “The Billion-Dollar Molecule,” which debuted as Crews was working in Schreiber’s Harvard lab. It’s blurbed as “a fascinating, no-holds-barred account of the business of science.”
“We all read it,” says Crews.
He began investigating how his own research could apply to the commercial world. The story began with a failure at one of the country’s biggest drug companies.
Bristol Myers Squibb had identified a naturally occurring anti-tumor compound – it worked, but they didn’t know how. If the company couldn’t figure out the mechanism of action, it was unlikely to be approved as a commercial drug.
Bristol Myers ultimately decided not to pursue the idea, published a paper, and closed the file on it.
Enter Craig Crews.
“I saw the paper and said, ‘hey, my chemists can make that molecule, and my biologists can figure out how it works,’ — and that’s what we did,” he said.
He published several papers from the research, helping him get tenured at Yale. But the idea wouldn’t let him go.
He believed the technology at the basis of the work, a proteasome inhibitor, could be an improvement on the drugs currently on the market for certain cancers.
“My lab is moving on to something else, but maybe I could help these patients,” he thought.
In 2003, he worked with Dr. Raymond Deshaies from the California Institute of Technology to found Proteolix. It was his first up-close experience seeing a compound in the hands of professional drug developers.
“They took my molecule, they tweaked it, they turned it into a drug candidate,” he said. “Now it’s approved by the (Food and Drug Administration) for multiple myeloma — it’s helped hundreds of thousands of patients. That got me excited that what we’re doing in the laboratory is not as esoteric as I imagined.”
Proteolix was purchased by Onyx Pharmaceuticals in 2009 for $850 million. Onyx was subsequently acquired by Amgen, which has brought the anti-cancer drug, Kyprolis, to market.
The success of that first startup gave him fuel for another attempt, and in 2013 he founded Arvinas, based on years of research into protein degradation as a technique to target disease.
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For his work on Arvinas, Crews in 2013 was named “Entrepreneur of the Year” by CURE, the state’s bioscience cluster now known as BioCT.
Arvinas undertook a successful IPO in 2018, raising $120 million. It has a strategic partnership with Pfizer, and currently has a number of cancer drugs in clinical trials. Crews remains both a shareholder and consultant to the company.
Arvinas was followed by two more drug-discovery companies, Halda Therapeutics, now four years old and based at New Haven’s Science Park, and Crews’ latest venture, Siduma Therapeutics, which has labs downtown at 55 Church St.
“That’s still in stealth mode,” he says. “It’s a novel idea from my laboratory.”
Creating value
This experience as a serial entrepreneur has brought differences between the academic lab and the world of commercial science into high relief.
“In academia I’m paid to be curious,” he said. “That’s not the job of a company. The job of the company is to create value. There’s a real-world urgency that requires a super focus.”
He has put that perspective to good use helping others at Yale translate their research beyond the lab.
“He’s probably the most sought-after faculty member at Yale by others who are contemplating making a startup company out of their research, and he’s incredibly generous with his time advising others,” said Josh Geballe, managing director of Yale Ventures, which works to turn Yale University research into real-world products and businesses.
Crews says one of the things he can bring is a good eye for what will excite venture capitalists.
“They get so many different opportunities presented to them,” he said. “They’re looking for the most de-risked opportunity. And so, if I can help academics in the state de-risk their science, it’s only going to accelerate faculty entrepreneurship.”
And as big pharma companies continue to cut back on basic R&D, looking to startup biotechs for likely drug candidates, he says the so-called “valley of death” is now the most serious impediment to progress.
“The bottleneck for drug development is getting things out of the academic lab, into a biotech,” Crews says.
Geballe points to Crews’ commitment to New Haven as another way he’s giving back. Three of his four companies were founded, and have remained, in New Haven — even Arvinas, which since its 2018 public offering has hit the big time.
“He insisted that Arvinas stay locally in New Haven when most of the investors told him he should base the company up in Cambridge, Massachusetts,” said Geballe.
In fact, Crews wants to deepen his impact on the city where he’s lived for 28 years.
Benefitting equally
At Science Park, Arvinas shared a parking lot with ConnCAT, an organization that provides job-training programs for unemployed and under-employed adults in the city. It was run by the indefatigable Erik Clemons, who has made it his mission to empower people from marginalized communities.
As soon as Clemons was introduced to his new neighbor, “it was clear to me that (Crews) has a huge heart for people. He’s not just a science guy who thinks deeply about equations. He also thinks about the human condition, especially those who are less fortunate than he is.”
The meeting and their subsequent discussions about equality of opportunity sparked a new idea for Crews.
“I am starting companies, I’m creating jobs,” he said. “But I haven’t seen all of the communities of New Haven benefit equally from the successes of my companies.”
In fact, life sciences generally have a racial integration problem. According to a recent report from BioSpace, Black people make up only 6% of the life science workforce, despite being 13% of the U.S. population.
“I’m the product of the first wave of school integration in the seventies,” says Crews. “A racially integrated society is my norm. There’s an economic divide that could benefit from a stronger Black and Brown middle class.”
He decided an industry problem needed an industry solution. He calls it BioLaunch.
“I realized that there are a number of positions in my companies for which a college degree really isn’t necessary,” he said. “The idea of BioLaunch is to train non-college-bound, 18- to 26-year-olds in research operations that support all of the other programs that are going on in a company.”
Clemons, who has worked in the job-training space for decades, applauds Crews willingness to really do the work.
“A lot of folks who want to help, they’re not willing to listen,” Clemons said. “Listening is the first part of help. And his willingness to sit in the trouble of poverty, and listen to people — a lot of folks are more than willing to help, but they don’t want to be in proximity to the poverty.”
BioLaunch just graduated its first cohort of trainees, all of whom have been placed in local companies, including one at Crews’ own Siduma Therapeutics.
Just one more way in which he’s creating impact through innovation.