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Global Blood Therapeutics, Third Rock Ventures’s First West Coast Startup, Gets $41 Million


6/14/2012 7:55:05 AM

San Francisco Business Times by Ron Leuty, Reporter

Drug developers talk a lot about “large patient populations,” “unmet medical needs” and a “clear path to approval.” Yet sickle cell disease, one of the knottiest diseases meeting all those criteria, has gone years without a breakthrough commercial treatment.

That might prove an advantage for Global Blood Therapeutics Inc., the first company birthed by Third Rock Ventures LLC’s West Coast office.

Third Rock and Global Blood announced Thursday morning that it is backing the South San Francisco startup with $40.7 million in Series A financing to discover and develop oral small molecule drugs to treat sickle cell disease and other conditions involving funky-shaped blood proteins. Essentially, its drugs will aim at pushing those proteins into healthier shapes that change the course of the diseases.

Most of today’s sickle cell treatments target symptoms of the disease – namely severe pain and infections – that in the United States largely strikes blacks and Hispanics. Hydroxyurea, which reduces a number of sickle cell complications, was approved in 1998, for example.

Scientists have long known that sickle cell disease is caused by a single genetic mutation, and diagnostics have helped zero in on people at risk of developing the disease. Meanwhile, there has been a lot of research around cord blood, stem cells, transfusions and gene therapy.

Yet there still is no widely available, effective cure for a disease can lead to kidney failure, stroke and shorter lifespans. Cord blood treatments, for example, can cost hundreds of thousands of dollars.

So why does Global Blood think it can succeed? If nothing else, because of people, timing and creativity.

“There really has been a lack of imagination,” said Mark Goldsmith, the former CEO of Cambridge, Mass.-based Constellation Pharmaceuticals who is returning to the Bay Area as a venture partner at Third Rock. “I don’t think people have dreamed in the way they need to.”

Goldsmith, Global Blood’s CEO, treated sickle cell patients while training and becoming part of the faculty at the University of California, San Francisco.

“It was not a pleasant experience … because the impact we had was modest and responsive to an acute crisis,” Goldsmith said. “When we discharged somebody, we knew they would be back.”

There are 100,000 sickle cell patients in the United States and more than 15 million worldwide, according to Global Blood.

Instead of focusing on treating acute episodes where sickle cell symptoms flare up and send patients to the hospital emergency room, Global Blood is looking at a long-term therapy that may stop healthy doughnut-shaped red blood cells from taking their sickle or crescent shapes. Those unhealthy, gloppy cells clog blood vessels and lead to conditions like stroke.

Global Blood is combining biochemistry, structural biology, screening and computational biology in its quest for a therapeutic. Some of the tools in those fields simply weren’t available several years ago.

What’s more, Global Blood is taking what’s called an “allosteric modulation” approach to sickle cell disease by targeting a point on the hemoglobin molecule that is not actively being altered. From that spot, Goldsmith said, the company’s drug can coax the red blood cell into a healthier shape.

The drug might even be useful as a preventive treatment, Goldsmith said.

Although Goldsmith is leading the company, Global Blood’s heart beats with Charles Homcy, who joined Third Rock in 2010 after stepping down as CEO of South San Francisco’s Portola Pharmaceuticals Inc.

Boston-based Third Rock, one of the most active venture capital firms in early-stage life sciences companies over the past few years, opened its Bay Area office in 2010 in San Francisco’s Mission Bay biotech enclave.

Soon after joining Third Rock, Homcy started talking to researchers across Third Street at UCSF’s Mission Bay campus about a startup focused on sickle cell disease. Those discussions ultimately led three UCSF scientists to join Homcy as co-founders of Global Blood: Matthew Jacobson, a professor of pharmaceutical chemistry; Andrej Sali, a professor of bioengineering and therapeutic sciences; and Jack Taunton, associate professor of cellular and molecular pharmacology.

Global Blood’s founders also include David Phillips, who co-founded Portola Pharma and COR Therapeutics with Homcy, and Third Rock’s Craig Muir.

Global Blood’s early team also includes former Incyte Corp. chief drug discovery scientist, Brian Metcalf, who is the company’s acting chief scientific officer.

Eight-employee Global Blood, which has carved out a temporary home in Cytokinetics Inc.’s headquarters, in the fall will land in its own space in South San Francisco. Eventually, it will be joined by other Third Rock portfolio companies.

The timetable for Global Blood’s first potential product, however, isn’t as clear. Goldsmith would not disclose a specific development timeline, but the company and Third Rock have done some work while assembling the company.

“We’re in this for real,” Goldsmith said. “We’re taking a very aggressive approach.”


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