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Bonded by blood
April 2013
by Lori Lesko  |  Email the author
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SAN FRANCISCO—Global Blood Therapeutics and Boulder, Colo.-based Array BioPharma Inc. have launched a drug discovery collaboration agreement aimed at identifying small-molecule lead compounds to target chronic blood-based diseases. Specific diseases to be explored in the joint venture were not disclosed.
 
The joint agreement, announced March 5, calls for Array to develop assays and screen its proprietary lead generation library of 300,000 small molecules to identify both active site and allosteric modulators of certain Global Blood targets. Array's library allows for rapid hit confirmation and subsequent lead optimization.  
 
Array's major focus centers on leukemia, while Global Blood is committed to finding more effective treatments for sickle-cell disease (SCD), a blood disorder affecting 100,000 people in the U.S. and more than 15 million worldwide.
 
"We look forward to deploying our drug discovery platform and sharing our expertise with companies like Global Blood," Kevin Koch, Array's president and chief scientific officer, stated in a news release. "Our mutual goal is to accelerate the drug discovery and development process by combining Global Blood's expertise in disease biology and computationally supported medicinal chemistry with Array's established drug discovery platform."
 
SCD is one of the earliest, rare genetic diseases to be defined on a molecular basis. It is caused by a single mutation that alters the oxygen transport protein hemoglobin and results in the "sickling"—or change to a crescent shape—of red blood cells. SCD has very limited treatment options, and there are essentially no therapies that directly address the underlying mechanism of the disease.  
 
Global Blood was founded to "revolutionize the treatment of severe, chronic diseases of the blood, and is applying class-leading approaches to drug discovery in order to develop entirely new therapies for diseases with limited treatment options today," says Brian W. Metcalf, the company's chief scientific officer.  
 
"Global Blood Therapeutics has previously disclosed its program focused on modulating hemoglobin in order to ameliorate sickle cell disease, and this program is progressing well," Metcalf tells ddn. "The collaboration between Global Blood and Array is focused on multiple blood-based diseases, but specific indications and targets have not been disclosed."  
 
Global Blood's lead program "is developing oral small molecules that directly engage the altered form of hemoglobin in patients with SCD and modulate its shape in order to overcome the adverse effects of the underlying mutation by normalizing the function of the this essential protein," Metcalf says. "Such a drug is intended to be used chronically to reduce or prevent the chronic manifestations of SCD, thus shifting the disease from the current treatment paradigm focused on episodic, acute intervention toward a long-term paradigm with greater benefits for patients."  
 
It was "through the relationships of the company's founders and key investor, Third Rock Ventures LLC, that Global Blood and Array formed a multitarget collaboration to identify small-molecule lead compounds," Metcalf says.  
 
Third Rock Ventures, a venture capital firm with offices in Boston and San Francisco, provided $40.7 million Series A financing for the formation of Global Blood Therapeutics. Dr. Mark A. Goldsmith, the firm's CEO, is also a venture partner at Third Rock Ventures and a medical doctor with experience treating sickle-cell patients.  
SCD has gone years without a breakthrough commercial treatment. Most of today's SCD treatments target symptoms of the disease—namely severe pain and infections—that in the U.S. largely strikes blacks and Latinos. Hydroxyurea, which reduces a number of SCD complications, was approved in 1998, but little progress has been made. There is no effective cure for the disease, which can lead to kidney failure, stroke and shorter lifespans, says Goldsmith.  
 
"There really has been a lack of imagination," says Goldsmith, who treated SCD patients during his training and as part of the faculty of 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. When we discharged somebody, we knew they would be back."
 
Code: E041324

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