Looking for genetic modifiers “hiding in plain sight” linked to ALS and other diseases.
CEO: Jason Coloma, Ph.D.
Based: South San Francisco, California
Clinical focus: Protective gene-gene interactions dubbed “genetic modifiers”
The scoop: Maze Therapeutics is working on the flip side of synthetic lethality. Rather than targeting gene-gene interactions that kill cells, Maze is going after genetic combinations that stop people from developing deleterious phenotypes. That focus grew out of a series of questions sparked by the latest use of genetic tools and large-scale databases.
“If you have a disease-causing gene and I have the disease-causing gene, why is it that you may be healthy and I may be sick? Are there other genes that come into play that provide a protective effect? Is there a drugging strategy to recover normal phenotype and recover from the illness?” Maze CEO Jason Coloma, Ph.D., said.
What makes Maze fierce: Throughout its short history, Maze has prepared itself for whatever is next on its agenda by pulling together supergroups of leaders. To start, Third Rock Ventures hit upon the idea of targeting protective gene-gene interactions by bringing together genetics experts including Mark Daly, Ph.D., Stephen Elledge, Ph.D., and Jonathan Weissman, Ph.D., to discuss the latest advances in their field.
Then, when deciding how to fund Maze, Third Rock eschewed the standard biotech-building strategy of handing over up to $50 million for early-stage work, choosing instead to bring other VCs including Arch Venture Partners and GV on board to gather $191 million for a broad, multifront R&D agenda.
Maze has taken a similar approach to building its team. Tim Behrens, M.D., and Matt Brauer, Ph.D., who used to respectively head up human genetics and data science at Genentech, came on board early, leading to the arrival of other researchers from the storied West Coast biotech pioneer. Maze supplements this expertise by tapping its scientific founders and board members, including Richard Scheller, Ph.D., for input.
The result is a biotech designed to execute an ambitious, two-pronged strategy. In the near term, the most visible part of Maze’s R&D operation will be its efforts to move five programs toward the clinic.
Maze established the programs by looking for genetic modifiers that were “hiding in plain sight,” Coloma said, thereby enabling it to cut the time taken to get into the clinic. Coloma expects a gene therapy based on Aaron Gitler’s amyotrophic lateral sclerosis research to enter IND-enabling studies next year. One, maybe two, of Maze’s four other programs will also get to that stage in 2020. The other drugs are small molecules targeting areas including metabolism, the kidneys and glaucoma.
The other prong of Maze’s R&D strategy is focused on finding new targets. This group is harnessing genetic databases such as UK Biobank and FinnGen, functional genomics tools including CRISPR and Perturb-seq and data science technologies to generate an ongoing pipeline of opportunities. Maze, which is open to working across disease areas and modalities, aims to prove the principle behind the R&D group by moving at least two concepts into drug discovery in 2020.
Maze is growing quickly to support these activities. Having exited stealth in February with just under 30 employees, Maze expects to close out 2020 with a headcount of 60, putting it ahead of its hiring plans. The team is currently working out of biotech hotspot The Cove At Oyster Point but has signed a lease on another site that will house up to 200 people.
As those numbers suggest, Maze is operating at a scale and resource level that frees it from some of the constraints biotechs typically face. That is informing how Coloma and his colleagues think about partnering.
“We have the flexibility to think differently. We like to think of ourselves as part of this new breed of biotech companies that don't have to do traditional business development deals,” Coloma said. “I think we would be looking towards trying to do more creative type of dealmaking in 2020.”
Investors: Third Rock, Arch, GV, Foresite Capital, Casdin Capital, Alexandria Venture Investments and undisclosed “crossover-type investors.”