Kent Mouw was still completing his clinical training when he first saw the data that would inspire some of his most exciting research. It was 2014, and a team of oncologists had arrived at the DNA repair lab where Mouw was working at the Dana-Farber Cancer Institute (DFCI). The oncologists, also from DFCI, were studying “exceptional responders” – patients who react dramatically better than others to certain drugs. They had found a group that was essentially cured of bladder cancer by platinum chemotherapy, which didn’t work as well in other patients.
All of the patients who had a certain genetic mutation — one that broke a protein and interfered with DNA repair — saw long-lasting clinical benefits from the chemo drug. The statistical signal from the data was “so strong,” says Mouw, “that the pessimist in me thought it might not be credible.”
The finding was in fact real. But the oncologists had hit an impasse. No one knew why the mutation seemed to make the patients hyper-receptive to platinum. If the biology could be understood, perhaps someday a drug could mimic the platinum-enhancing effect in patients who didn’t carry the mutations — essentially curing them too.
It was a daunting goal, but the oncologist leading the genomics team, Eli Van Allen, wanted to pursue it — and so did Mouw. The collaboration was on.
Fast-forward to summer 2019: Mouw and Van Allen had both become assistant professors at DFCI, and had thoroughly investigated the biology of the broken gene. But they had hit another impasse: their findings were now too mature to be further supported by traditional grants, yet not validated fully enough for most pharmaceutical companies to invest in.
Mouw and Van Allen didn’t know it yet, but two other groups were trying to bridge a similar translational gap: the leaders of the Broad Institute’s Center for the Development of Therapeutics (CDoT), and a savvy group of life sciences investors at Novo Ventures.
Burt Adelman, a former head of R&D at several pharmas, had recently joined Novo’s Boston office. He was pushing the firm to strengthen its focus on early-stage investments, especially given its prime location in the heart of biotech. He dreamed of a portfolio-in-a-portfolio, in which early-stage ideas would be de-risked by both genomic research and the interdisciplinary expertise of leading academics. “I was trying to get Novo more deeply involved in the best science, the novel and early-stage ideas,” he says, “and get us more broadly connected in the Boston biotech community — all in one shot.”
Meanwhile, Issi Rozen, Broad’s chief business officer, was trying to figure out how to fund more emerging science at CDoT. “The Broad’s mission is to propel the understanding and treatment of disease,” he says. “Having a bridge that involves the biologists in the early stages of drug discovery is a critical component of that mission, because it increases the likelihood that the basic science will be translated.”
CDoT was acting as that bridge -– “In its capabilities, expertise and, partnerships, CDoT functions like a biotech,” Rozen says –- and it sought to accommodate more projects to help ensure that many of them would succeed. That would take both the right kind of funding (and plenty of it), and the right kind of life sciences investment expertise to guide successful projects toward the clinic. Novo had both.
By early fall, all the pieces had come together: Novo had committed up to $25 million over five years towards a “Greenhouse” at Broad that would push early-stage research through CDoT. It had defined what it was looking for: smart people with big ideas for solving important problems, and proposals that were risky enough to be exciting, but supported by both genomic evidence and the wisdom of Broad’s scientific leaders. And it had realized that there was no shortage of those projects — they had just been waiting for the right partnership to drive them forward.
Today, with capacity for 10 projects at a time, the Novo Broad Greenhouse is already half-full. Mouw and Van Allen’s work is one of the projects; with Novo funding, the researchers will develop a way to sift through thousands of small molecules to find one or more that mimics the platinum-enhancing effects of the broken gene. “It’s compelling, it’s straightforward, you can really get your hands around the whole pathway — it’s an exceptional opportunity,” says Adelman. “And as one of the first projects, it’s going to teach us a lot.”
For their part, Mouw and Van Allen are thrilled. “Trying to come up with a sensitizer to an old-fashioned chemotherapy isn’t the most traditionally obvious thing to do. And it’s pretty high-risk,” says Van Allen. But, he adds, platinum therapies are very widely used. “If we could increase their effectiveness across cancer types — well, it would be incredible.” And, now, also credible.