Sure, things may look great now, but it wasn’t long ago that Kendall Square was a biotech ghost town—and the good times might come to an end if we’re not careful. Meanwhile, gene therapy, cell therapy, and microbiome research look poised to make an impact on healthcare—just don’t overlook the hurdles that remain, or underestimate how long it’ll take to clear them.
In other words, we’re making progress. But people should be realistic about that progress—biotech isn’t as easy as making iPhones.
That was a thread that pervaded “What’s Hot in Boston Biotech,” our latest event, at the Broad Institute of MIT and Harvard this week. A cadre of the area’s top scientists, entrepreneurs, and investors went over some of the ups, downs, and issues still-to-come for several emerging (and re-emerging) areas of life sciences innovation. Some examples: could carrier testing be a threat to gene therapy? What discovery is synthetic biology whiz and MIT professor James Collins most intrigued by? And why is the concept of “precision medicine” really just the start of a long slog that might reshape drug development?
A huge thank you to our speakers and moderators: David Altshuler of Vertex Pharmaceuticals; Susan Lindquist of the Whitehead Institute; MIT’s Collins; Noubar Afeyan of Flagship Ventures; Alexis Borisy of Third Rock Ventures; Tony Coles of Yumanity Therapeutics; Samantha Singer of the Broad Institute; Olivier Danos and Adam Koppel of Biogen; Michelle Dipp of OvaScience; Peter Kolchinsky of RA Capital; Marian Nakada of Johnson & Johnson Innovation; Amir Nashat of Polaris Partners; Bernat Olle of PureTech; Steve Paul of Voyager Therapeutics; Ben Auspitz of Fidelity Biosciences; and Chuck Wilson of Unum Therapeutics.
Thanks also to our event hosts, Biogen and the Broad Institute; our event sponsors, American Laboratory Trading, Fairfax County Economic Development Authority, Cote Orphan, and Mintz Levin Cohn Ferris Glovsky and Popeo; and to Keith Spiro of KeithSpiroPhoto for the photos (those will be coming soon).
This was a blowout event, a tough one to recap, so here are just a few snippets—seven in total—to whet your appetite for next time.
1. Be on the lookout for the latest startup out of Jim Collins’s lab at MIT. Collins is already behind a few synthetic biology startups, Sample6 and Synlogic. What’s next? He described a technology capable of opening up a cell, extracting the machinery, slapping it on paper, and freeze drying it—after which it could be stored at room temperature until it’s rehydrated, when that cellular machinery would function “as if it’s inside a living cell” again. Collins says this technology could be used in several ways—like cheap, quick diagnostics for antibiotic resistance, oral vaccines, or as therapeutic peptides or proteins. “That last one is probably the one I’m most excited about, for sure,” Collins said.
2. “I chose to go into neurodegenerative diseases because they were the darn hardest.” That was Susan Lindquist on Yumanity’s decision to target things like Parkinson’s and amyotrophic lateral sclerosis—biologically complex diseases which have stupefied scientists for decades—with its yeast-based drug discovery system. It’s a tall order, and Lindquist and co-founder Tony Coles know they’re taking a risk.
As Coles said, “When I die, what will be on my tombstone, will it be that I held some great jobs? Or that I wanted to make a difference?” That means Yumanity will face some skeptics. As Peter Kolchinsky questioned, are today’s animal models—which often fall short of representing human neurological disease—even good enough to validate the things Yumanity finds, or will the company just “take a leap of faith” that what it sees in cells will translate to humans? “If you have a defined patient population in which you know that that compound is fixing that patient’s [disease], I think it very well will be possible to go directly into patients—as long as you’ve done your toxicity studies,” Lindquist responded.
3. CAR-T therapy is promising, but the hurdles remaining are significant. As Chuck Wilson noted, most of the exciting data generated by chimeric antigen receptor T-cell (or CAR-T) therapy so far have come from small indications—specific types of blood cancers like acute lymphoblastic leukemia, not much more prevalent cancers of the breast and lung. How broadly effective can it be? How can it be scaled commercially—so folks scattered across the country can use it, not just a few people at a major academic center?
Wilson cautioned it’s taken three decades of work on engineering cell therapies—the first CAR was made in 1989—and the viral vectors used to deliver them, just to get to the point that even a few people have seen dramatic results. Patience, and more tinkering, is required. “The advantage right now is that in many ways we have all of those pieces in place,” he said. But “as we go into solid tumors, additional kinds of engineering [and] modifications are going to be useful in seeing the potential for these kinds of therapies…and new technologies like gene editing may have the potential to enable some of those modifications.”
4. Boston biotech’s biggest challenge? Scale. Noubar Afeyan remembers making the trek out to San Francisco “with envy,” seeing how the Bay Area first dominated the computer industry and then became a biotech powerhouse. But Boston (“and by Boston I really mean Cambridge,” he joked), has surged to become arguably a bigger biotech power, something Afeyan said was due to a sea change in attitude—more courage to pursue ideas even if they might not work.
The biggest worry in maintaining this momentum? Scale. Rent prices have surged to $90-$100 per square foot, there’s no affordable lab space “within a functioning T distance” (Boston’s train system). That’s an issue the area is going to have to confront if the good times are to continue. “I don’t think Boston will remain the Silicon Valley of biotech if it doesn’t continue to scale,” Afeyan said. “We need to think ahead about what maintains this, what makes this sustainable.”
5. Gene therapy’s limitations, and its “left field” enemy. Despite gene therapy’s re-emergence, and all the technological advances that have been made (particularly in how these therapies are delivered), Olivier Danos and Steve Paul warned of its limitations; Paul called gene therapy a “resurgent old field” that is still “in its early days.” It’s very limited; gene therapy can’t tackle difficult diseases—diabetes, for instance—and a number of advances will have to be made before it can. Those delivery systems, or vectors, are much better than they used to be, but are still evolving—“we’ll be talking about very different vectors 5 or 6 years from now,” Paul said.
But what if, by the time those vectors are ready, gene therapy doesn’t have the same audience? Kolchinsky theorized, for instance, that if carrier testing—genetic tests for prospective parents—becomes commonplace, perhaps the number of people born with monogenic disorders (the supposedly easier targets for gene therapy) will shrink. And perhaps that will force gene therapy companies to evolve, and try to crack harder, polygenic targets.
6. Deals are really about relationships. In a way, Vedanta Biosciences and Johnson & Johnson gravitated towards one another. The startup is developing microbiome therapies for immunology, and that’s right in J&J’s wheelhouse. But the deal the two cut in January was a result of personal relationships, not just strategic alignment. For one, Vedanta’s founders at PureTech began talking to J&J before the company was even incorporated. That familiarity came in handy when J&J opened up its Boston Innovation Center in 2013. While the center was being built, its Boston team “needed a place to crash,” said PureTech partner and Vedanta chief operating officer Bernat Olle, “so they took some offices at PureTech—and the relationship became hyperlocal.”
That gave J&J an important inside track. As Vedanta moved forward, it was approached by other VC groups aiming to form a syndicate, and then pharmaceutical companies looking to make a deal. Vedanta chose a licensing deal with J&J—in part because it knew the people involved, and what they wanted to do with its lead drug. “When you’re sharing your baby, all these considerations come to mind, but knowing what was in the mind of the people that were going to drive the project forward was valuable,” Olle said.
7. Give “Precision Medicine” (a lot of) time; it just might change drug R&D. President Obama’s Precision Medicine Initiative sounds great in theory; through evolving science, genomic understanding, and data collection, someday we’ll all get the drugs that specifically target the genetic problems that cause our diseases, and that starts with matching specific genetic defects with disease with the help of a massive database. But as David Altshuler said, that’s only step one, which, “while foundational and vastly important,” leads to understanding, not medicines. Step two is discovering a therapeutic, which takes another three to five years; step three, developing and testing it, takes another 10 years and hundreds of millions of dollars.
All of which is why Altshuler bristles at the idea that genomics hasn’t delivered the goods because R&D productivity rates for drugmakers remains low.
“We’re just now entering the era where we understand disease well enough,” he said. “We’ll learn over the next 10 or 20 years what the true success rates can be when you have a human biologically-focused, genetically enabled therapeutic strategy.”