Some people with disease-causing genetic mutations seem to escape illness, while members of a family with the same genetic aberration present with different forms and/or severity of a disease — for example cystic fibrosis. These inconsistencies suggest that the effects of a single genetic variant can be modified by other genes in our DNA, and monogenic diseases give scientists the opportunity to identify these genetic modifiers and harness them for therapeutic intervention. A company working on translating these insights into drugs — Maze Therapeutics — burst on to the scene on Thursday, with a $191 million infusion led by storied investors Third Rock Ventures and ARCH Venture Partners.

The San Francisco-based company plans to combine the strength of large-scale human genetics with functional genomics to understand the ways modifier genes can confer protection.

“Almost two and a half, three years ago, we had a meeting with the scientific advisory board about whether the time was ripe to integrate these two capabilities, build a platform-based company, with the understanding that really the greatest risk in drug discovery is picking the right target — a target that will have quantitatively important, clinically meaningful outcome,” founder and interim CEO Charles Homcy told Endpoints News.

“The concept of finding genetic validation of a target, where the genome actually tells you what the target is — that it is another gene that modifies the dysfunctional activity of a mendelian disease (diseases caused by mutations in one gene), gives one great confidence that target as a drug discovery target will provide clinical benefit…that really is the raison d’être for this platform build at the company,” said Homcy, who is also a partner at Third Rock.

The company has about 3 to 4 drug discovery programs on the go, Homcy said, declining to provide detail on the diseases they are targeting. “We believe there was low-hanging fruit out there in terms of validated genetic modifiers…two of those programs will hopefully be in the clinic in two and a half years.”

The most advanced program is a small molecule targeting a classic mendelian disease, he added.

The company is called Maze for two reasons: the idea behind navigating the maze of human genetics as well as a way to pay homage to Nobel prize winner Barbara McClintock and her work with mobile genetic elements in maize corn. It sports a star studded group of scientific founders, including noted geneticists Mark Daly (Broad Institute) and Stephen Elledge (Harvard), Sekar Kathiresan (Broad Institute, Harvard) as well as neuroscientist Aaron Gitler (Stanford) and scientist Jonathan Weissman (University of California).

The capital raise also included the participation of GV (the venture capital investment arm of Alphabet), Foresite Capital, Casdin Capital, Alexandria Venture Investments and other undisclosed investors.

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Image: Charles Homcy. (Third Rock)