Ex-Epizyme CEO’s New Startup, Fulcrum, Nabs $55M For Gene Control Drugs

Xconomy Boston — 

Former Epizyme CEO Robert Gould is back with a new startup. A year after stepping down as the CEO of Cambridge, MA-based Epizyme, Gould has re-emerged to lead another Cambridge company, Fulcrum Therapeutics, which has secured a massive $55 million Series A round from Third Rock Ventures.

There are some similarities between Gould’s old job at Epizyme (NASDAQ: EPZM) and his new one. Gould spent five years leading Epizyme, one of several companies delving into epigenetics, a field of research focused on changes in gene expression. Likewise, at Fulcrum, he’s trying to discover and develop small molecule drugs aimed at controlling molecular switches that turn genes on or off, and thus can impact a variety of diseases.

That’s where the similarities end. Epizyme is developing drugs for cancer, a field Gould (pictured) says Fulcrum is specifically avoiding. Fulcrum’s goal is to treat a broad range of rare genetic diseases, starting with two that he says currently have no effective treatments: Fragile X syndrome—which is often associated with autism spectrum disorders—and a muscle disease called facioscapulohumeral muscular dystrophy (FSHD).

Gould won’t specify how far Fulcrum’s programs are from human clinical testing. He just shares that the $55 million round from Third Rock—a large amount, but fairly typical of Series A deals from the Boston VC firm—should get his company “into and beyond” animal testing.

Billions of dollars have been spent on research to understand and tweak the complex circuitry that causes genes to make various proteins in our bodies. The idea behind this work is to identify the key molecular switches that can cause a gene to produce, or not produce, a protein—and ideally use that knowledge to treat a disease.

A genetic error, for instance, leaves Fragile X patients without a protein called FMRP (fragile X mental retardation protein) that helps with brain function. Fulcrum aims to use a drug to flip a molecular switch so the aberrant gene produces FMRP. By contrast, a genetic problem causes patients with FSHD to overproduce a toxic protein that wastes away their muscles. Fulcrum aims to use a drug to stop production of that protein.

Gould says oncology was the “poster child” for drugs that regulate gene expression, from hormone therapy like tamoxifen to epigenetic drugs such as vorinostat (Zolinza). But the tools and genomic data are now available to apply the technique more broadly, he says. Another Boston-area company, for instance, Syros Pharmaceuticals (NASDAQ: SYRS), is similarly developing what it terms “gene-control” drugs for not just cancer, but possibly inflammatory diseases and rare genetic disorders as well.

“This is an emerging field that’s just starting to realize its full potential of treating human disease,” Gould says.

Enter Fulcrum, which Gould says aims to capitalize on the research already done in understanding gene regulation, and be part of the “next wave” of gene-regulation drugs. The company is combining a range of methods—from stem cell technologies to computational biology, screening tools, and readily available databases of genomic information—to do this type of work. In Fragile X, for example, Fulcrum would start with skin cell samples from patients with the disease, derive neurons from them, and use them to, as Gould says, “ask very specific questions” about how to cause those neurons to produce FMRP. The goal is for that work to lead to a drug target, and eventually a drug that can impact it in one way or another.

Fulcrum is a very early-stage company, of course, so it’ll be a while before it proves whether this approach will lead to something of value. But Gould, who worked at Merck for more than two decades, has shown he can build a startup and get it into clinical testing. He became Epizyme’s full-time CEO in 2010 and helped take the company public in 2013. He stepped down last August to make way for Robert Bazemore as the company began to put its first drugs in clinical trials. “The time felt right for me to transition the company to the next CEO,” says Gould, who is still an Epizyme board member.

Fulcrum’s scientific founders include Michael Green, who chairs the University of Massachusetts Medical School’s molecular, cell and cancer biology department; Danny Reinberg, an NYU School of Medicine biochemistry professor; Rudolf Jaenisch, a founding member of the Whitehead Institute for Biomedical Research; and Jeannie Lee and Brad Bernstein, both gene regulation specialists at Massachusetts General Hospital. (Lee is a founder of RaNA Therapeutics, another Boston-area startup focused on gene regulation).

Fulcrum has 10 employees but will double to 20 this year, and possibly grow to 40 next year, Gould says.