In today’s drug development environment, one might overlook natural products, dismissing them as relics of the past. But Cambridge, MA-based Warp Drive Bio is devoting its full attention to the old school of natural products in an industrialized effort to discover and develop therapeutics using decidedly up-to-date tools and technologies, such as next-generation sequencing and single-nucleotide manipulations.
“Humans have been dosing themselves with naturally occurring compounds for as long as there has been a human race,” said Gregory Verdine, Ph.D., CEO. However, he added, “The way we are discovering them is completely different from the way it was done in the past.”
Warp Drive was launched in 2012 through a partnership with Sanofi and with funding from Third Rock Ventures and Greylock Partners. Dr. Verdine, one of the firm’s co-founders, in July took a leave of absence from his post as a professor of chemistry and chemical biology at Harvard in order to take the wheel at Warp Drive, which has been fully funded for its first five years. Though he has been involved with many startups—including Eleven Biotherapeutics, Variagenics, and Vertex Pharmaceuticals—this firm is the only one he has assumed an operational role in.
Speaking with GEN, Dr. Verdine said Warp Drive devoted its first full year to perfecting its processes, systematizing microbial genomics to an extent that had not been possible before.
“In a way, the first year of Warp was spent showing that we could get everything under one roof, and that we could really make it work on the scale which is unimaginable. Before we began this, people had sequenced single bacterial genomes and inferred the compounds in them. There were a handful of studies in the literature in which that had been done,” he said. “To do it on the scale of thousands a month was something we had to convince ourselves that we could do.”
And in a mere seven months, he said, Warp Drive has found its flow. To date, the company has sequenced the genomes of more than 50,000 bacteria in its search for biosynthetic pathways whose outputs alter fungal physiology much in the same way they affect human physiology.
“Most of these really fundamental pathways you find in fungi are also fundamental in humans,” Dr. Verdine said. “The sequence similarity between the fungal proteins and the human proteins…is usually so high that when you find a molecule that exerts a potent effect on fungi, it often exerts a potent effect on human cells by exactly the same pathway.”
But sequencing GC-rich microbial genomes, challenging as that may be, is but a part of the company’s efforts. With sequence assemblies in hand, Warp Drive is performing what it calls a “genomic search”—extracting biosynthetic pathways of interest. This step, Dr. Verdine said, “is sort of like looking through a blueprint for a very particular type of machine on a factory floor.” Having identified the DNA encoding the entire pathway of interest, the team clones it, using genome-editing techniques to make manipulations at the single-nucleotide level. From there, purification and target identification/mechanism-of-action studies are performed.
“Every single one of these operations is completely interdependent on the operation that came before it,” Dr. Verdine said. “It’s the convergence of all these unique areas of expertise and really getting them to work with each other that makes this such an extraordinary operation.”
In essence, Warp Drive is bringing natural products up to speed in the genomics era. And that’s part of the story behind how the firm got its name.
When the company was incorporated, Dr. Verdine chose its name as a placeholder. “I thought: We’re basically taking this field and putting it through a time warp…so I said ‘Let’s call it Warp Drive’—because we were providing that propulsion,” he said. However, it was because of Sanofi’s global R&D president Elias Zerhouni, M.D., that the name stuck.
“Elias loved the name. He loved it so much he began using the term ‘warp speed’ at Sanofi,” Dr. Verdine explained. Eventually, he added, “people in Sanofi started calling Elias ‘Warp Speed’—that became his nickname. I think he loved it because it really symbolized what he was trying to do in Sanofi when he came in.”
What Dr. Verdine is trying to do with Warp Drive, he said, is not unlike what many firms are doing in the systematic search for biologics. “Acquiring sequence information, assembling sequence information, figuring out how to search it effectively, moving genes around [is] something that people have shown you could do, but had not been in any way industrialized,” he said. “So we had to show that we could do all of that…and that, when we did the sequencing, we could prove that there were novel, exciting molecules hiding in plain sight in the genomes of these bacteria.”
Though fewer are submitted, when it comes to FDA approvals, natural products outperform their synthetic counterparts. But natural products are not without their problems. Without critical discoveries related to deconstructing complex biosynthetic pathways and advances in assembling highly repetitive genomes made largely in academic labs, Warp Drive scientists may not have even fathomed attempting what they have been able to accomplish thus far.
“As pharma was abandoning it [natural products], academic groups had effectively reinvented the field from the ground up,” Dr. Verdine said. “And we capitalized on those findings in the academic world. That set of discoveries—and also the access to ultra-high-throughput DNA sequencing—made it possible to do what Warp is doing.”