By Pierre Valette, Emmy and Peabody-Award winning journalist and TV producer
Photographer: Gabe Souza
Soil. Laurence Reid is obsessed with it — more specifically — he’s obsessed with the microbes in it.
Laurence Reid is the kind of CEO who is able to talk for hours about his obsession. “If you dig around in the soil, there are multitudes of different microbial species living in it that use very sophisticated chemicals to fight and defend themselves. And that huge source of microbiology can be used to find critical new drugs.” Reid is the CEO of Warp Drive Bio whose mission it is to leverage the natural chemistry found in soil. Like the name of his company suggests, he’s committed to developing new drugs — especially antibiotics — at warp speed.
“If we don’t respond immediately to the problem of growing drug-resistant bacteria, by 2050 as many people could die from bacterial infections as die from cancer.” He’s confident that Warp Drive can effectively contribute to addressing this problem. And he knows that in order to succeed, he’s in exactly the right place.
“In Boston, I have the ability to pick up the telephone and get advice from a CEO that I either know, or even someone I’ve never met before,” Reid says. “We’re competing one day and then collaborating the next, and yesterday’s competitor is tomorrow’s colleague. It’s a very fluid community.”
In recent years, Boston has become one of the most fertile environments for biotech innovation in the world. This innovation is fueled by the region’s 122 colleges and universities, including five of the top six National Institutes of Health-funded academic medical centres, and what Bob Coughlin, President and CEO of the Massachusetts Biotech Council (MassBio), calls a “true collaboration between industry, academia, and government.”
According to Coughlin, recent strategic partnerships between local biotechs and global health and pharmaceutical companies, such as Roche, have accelerated research and development in Boston at a pace that would have been inconceivable 20 years ago.
Last fall, Roche announced a partnership with Warp Drive Bio to test and further develop the company’s discoveries. Roche has similar partnerships with two other Boston companies, Blueprint Medicines and C4 Therapeutics, whose groundbreaking work could eventually result in new life-saving drugs. To build upon such partnering efforts, Roche recently established its first partnering presence in Boston.
“Boston is an extraordinary place for accelerating the discovery of critical new drugs,” says Michael Crowley, Head of Roche’s early stage partnering team, Innovation Partnering, and the driving force behind Roche’s new Boston partnering office, “In the Boston area, you have many highly inventive, nimble companies working in an ideal environment to quickly translate novel science into new medicines. Roche can support what these companies do best — the rapid research and development of groundbreaking drugs — while providing the necessary scale and complementary expertise to bring new drugs through clinical testing, and eventually to patients.”
The work Warp Drive Bio is doing Reid says, continues decades’ worth of scientific research into “the chemistry of nature.” Historically, scientists tapped microbial sources to come up with some of most transformative drugs in the world, such as penicillin. But over the past decades, research into those sources slowed down. The solution, Reid believes, is to return to existing microbial sources, prospecting for novel drugs more efficiently than ever before.
Warp Drive’s approach is a combination of insight, big data, and computational firepower the company calls “Genome Mining.” This approach digitally canvasses the DNA of hundreds of thousands of microbes, then uses predictive algorithms to hypothesize which of those molecules are most likely to become antibiotics. Once Warp Drive isolates the genetic code of those molecules, researchers can synthesize them in the lab.
“We think researchers were just scratching the surface,” says Reid. “They were probably playing with only about a quarter of the synthetic capacity of these microbes. We can get to the other 75 percent.”
Of course, predicting is one thing. Predicting correctly is quite another. Last year, Warp Drive tested molecules from the first ten clusters it had synthesized. For, Reid, this was his “holy s**t” moment. He remembers seeing the results back from the earliest tests showing that half of the clusters exhibited early anti-microbial activity. “Wow, this might really work,” Reid recalls thinking. “If the molecules we identify prove to be anti-microbial 50 percent of the time, we’ll have an off-the-scale success.”
Determining how and whether these molecules also will work in animals, and eventually in humans, is where Roche comes in. “We have a great, natural collaboration with their team in Basel,” Reid says. “All of the scientific work — the wet work — happens in collaboration with them, mainly in the Warp Drive lab but with input from both teams.”
Once a molecule is a year to 18 months away from being ready for human testing, he says, “Roche takes over.” Roche will be responsible for clinical development of certain initial molecules allowing Warp Drive to return to doing what it does best: mining and researching other molecules that will form the basis of a new generation of antibiotics.
While Warp Drive is identifying future antibiotics with potentially broad application, Blueprint Medicines is developing medicines for genomically-defined populations in oncology and rare diseases. “We find patients with severe cancers and other diseases, who might not have the most common type of mutation or gene alteration, and we try to find a treatment specifically for them,” says Jeff Albers, Blueprint’s CEO.
Currently, Blueprint is developing a treatment for the 5 to 7 percent of patients with aggressive gastrointestinal stromal tumours, or GISTs, who are unresponsive to the standard therapy. “Imagine you’re diagnosed with GIST, and you’re told that there is medicine, that might help you. But then they sequence you and you don’t qualify for the drug,” Albers says. If you have a specific genomic makeup for which this medicine does not work,” he says, “there’s no effective therapy and your life expectancy is about a year.”
Blueprint’s work focuses on kinases, enzymes that regulate biological activities in cells. Traditional kinase inhibitors often broadly hit multiple kinases. This can cause debilitating side effects, such as nausea, diarrhea, and low blood counts, and may still have little impact on the targeted disease.
Blueprint, by contrast, wants to be “exquisitely selective,” developing molecules that can precisely turn off specific kinases, Albers says. This approach requires a cutting-edge understanding of the biology of the hundreds of kinases that make up the kinome tree, and the ability to produce the chemicals that can inhibit them. Blueprint’s vision is to “design a selective inhibitor for every single kinase on the kinome tree.”
The beauty of Blueprint’s approach is that when new discoveries are made about the role of a specific kinase in a certain disease, Blueprint may already have synthesized compounds to inhibit that kinase. Jeff Albers refers to this as Blueprint’s “Wayne Gretzky approach”. “Good players go where the puck is, great players go where the puck will be.”
Blueprint has partnered with Roche, Albers says, in order to reach more patients in an area beyond genomically-defined cancers. While Blueprint understands how to create and optimise compounds quickly, the company needed more expertise in the role of kinases in cancer immunotherapy.
“Roche has that,” Albers says.
Now, Roche and Blueprint are working on multiple specific targets in which Roche has deep expertise and interest.
“I’ve been in many collaborations,” says Albers, “and this is what you hope for. It feels like a seamless partnership where we all contribute our expertise, and it doesn’t matter if we’re at Blueprint or Roche — we’re all working as one.”
Protein inhibitors are one way to address cancer growth. C4 Therapeutics (C4T) is exploring a different approach altogether, hoping to develop a new breed of game-changing drugs that degrade disease-causing proteins.
“We need new therapies,” says Andy Phillips, C4T’s CEO, who explains the difference between inhibitors and degraders with some colourful analogies. Traditional inhibitors, Phillips says, need to bind to proteins, very tightly, over a long period of time, which is frequently an ineffective approach to cancer-causing proteins as it is akin to “tying together the shoelaces of the cancer, slowing it down only temporarily.”
By contrast, he says, degraders identify the disease-causing protein, then recruit cellular machinery that puts “almost like Post-it notes on the protein that say, ‘Take me to the shredder I’m ready for degradation.’ And the cell takes over and destroys the protein. If degraders can work rapidly and comprehensively,” he says, “they can remove so much of the protein that the cancer cells can’t recover and often die.”
Degraders have been studied in academic labs, Phillips says, but no one has yet figured out how to turn them into successful drugs. The ability to turn these molecules into effective drugs has huge implications. One of the first potential indication of C4T’s own degrader is acute myeloid leukemia (AML). About 10,000 AML patients die every year in the United States because they are unresponsive to existing treatments.
“Helping patients like these has been a huge inspiration for me and everyone at C4T. It’s what drove my decision to leave academia and help lead this company.” As part of C4T’s plans to build an integrated research and clinical stage company, C4T partnered with Roche as a flagship partner, just as the company’s formation was announced in January 2016.
“C4T provides early discovery and development capabilities with 70 passionate people who live and breathe degraders and the science associated with them,” says Phillips. “What we needed was a partner who believed in degraders from the get-go, who wanted to engage in the science early on, and who are experts at the entire process of drug development. Roche is a great example of these points. They’re the world’s biggest oncology company for a reason.”
Roche and C4T are working on multiple projects. Through their partnership, Roche and C4T have advanced projects faster than Phillips thought was possible. A self-described skeptic, Philips reports that after success with Roche in the lab, he’s now comfortable saying, “Degraders are incredible and we hope they will be able to do remarkable things.”
C4T‘s work, like that of Blueprint and Warp Drive, is typical of Boston biotech firms: ambitious projects with hopefully significant consequences for patients and their families. Coughlin, the CEO of the MassBio, understands the value of that work on an achingly personal level. His son suffers from a rare disease. One of the drugs that successfully treats his son’s combination of mutations was developed recently by another company in Boston, at a pace Coughlin never would have imagined a few years ago.
“What makes this environment so amazing is the buzz, the excitement, and the fact that everyone is working to solve the unmet medical needs of patients,” Coughlin says. “What once seemed like science fiction is becoming a reality.”