Third Rock’s MyoKardia Gets $38M for Genetic Forms of Heart Disease

9/20/12Follow @xconomy

When Boston Celtics star Reggie Lewis dropped dead during a shootaround 20 years ago, little was known about his underlying heart problem. It took an autopsy to confirm that he had a genetic defect known as hypertrophic cardiomyopathy, which leads to thickening of the heart tissue and irregular heartbeats.

Years later, as a slew of genetic technologies have come together, Third Rock Ventures is betting $38 million that a startup called MyoKardia can make drugs that treat that underlying genetic defect, and others like it that affect 1 million people in the U.S.

MyoKardia, a new company setting up shop in San Francisco, is being led by Third Rock venture partner Charles Homcyand a team of top academic scientists who study the genetics of cardiovascular disease and muscle biology. The group of advisors includes James Spudich of Stanford University, Leslie Leinwand of the University of Colorado, and Christine Seidman and Jonathan Seidman, at Harvard Medical School.

Charles Homcy

The basic concept at MyoKardia is to connect the dots between abnormal genes, proteins, and tissues in certain genetically defined types of heart disease. As those connections become more clear, it will look to develop conventional small-molecule pills that work for certain segments of people with common gene mutations, and which people can take daily to keep the symptoms at bay, Homcy says. The initial plan is to go after hypertrophic cardiomyopathy and dilated cardiomyopathy, with a handful of drugs matched up to specifically treat a handful of different genetic forms of the disease. Longer term, the company hopes that work will be useful for more of the 5 million patients in the U.S. with congestive heart failure, who have a complex disease that may be the result of a complex interplay of genetics and environmental factors.

“This may be the first time that we can really get a sense of the mechanisms that regulate cardiac form and function,” Homcy says.

MyoKardia is getting started in San Francisco, Homcy says, partly to be near Spudich, who recently won the Albert Lasker award for his basic research for his studies of how muscles contract. Homcy also has a close connection in Boston to Christine Seidman, a former postdoc in his lab at UCSF, who he says later went on to “break open this field,” and is now a Howard Hughes Medical Institute investigator collaborating with her husband Jonathan at Harvard Medical School.

Treatment of heart disease has made strides over the decades with now-generic medicines that lower high blood pressure and reduce LDL cholesterol. While those drugs have been prescribed to millions of people, cardiologists haven’t been able to capitalize on deep understanding of the genetic roots of the disease in the same way cancer physicians or other specialists do, Homcy says.

That’s beginning to change, as researchers have been able to identify changes as subtle as a single amino acid that can have an impact on how the sarcomere, the basic unit of heart muscle, functions, Homcy says. The founding team of advisors will help take this work to another level, by enabling MyoKardia to develop new assays and protein expression tests which should provide a good understanding of the biology of disease, which chemists can then use to make specific drugs.

There are always a lot of unknowns in a project at this early stage of research. For starters, MyoKardia will want to know just how many different genetic variations are really the major culprits leading to these forms of heart disease. Scientists currently believe there are “hundreds,” Homcy says.

Rather than make a hundred different drugs for 100 genetically distinct diseases, MyoKardia hopes to categorize the genetic diseases into about five to seven different “buckets,” Homcy says, which would each have their own specific drug. Like Cambridge, MA-based Vertex Pharmaceuticals (NASDAQ: VRTX) has done with ivacaftor (Kalydeco), a drug for a rare form of cystic fibrosis, MyoKardia plans to start in a well-defined genetic population, and eventually develop more drugs and more combinations of drugs to help more patients, Homcy says.

Homcy said he doesn’t believe there are any competitors, even in Big Pharma, taking a similar approach to the genetic forms of heart disease. One other company, South San Francisco-based Cytokinetics (NASDAQ: CYTK), which Homcy used to serve as a board member, is working on drugs to improve muscle contractility, but is focused more on the muscle tissue than the genetics, Homcy says. Spudich is a co-founder of both MyoKardia and Cytokinetics.

MyoKardia is currently based out of Third Rock’s San Francisco office, and will be looking for space to grow in South San Francisco this fall, a spokeswoman says. Homcy, a co-founder of Portola Pharmaceuticals and a former head of R&D at COR Therapeutics, says he’s only doing the CEO gig part-time. As MyoKardia looks to grow, one of his important early tasks is to find a permanent CEO to replace him. “I’ll stay as long as necessary,” Homcy says. “But this company really needs a full time management team. There’s so much to do.”

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