SAN FRANCISCO—Global Blood Therapeutics and Boulder,Colo.-based Array BioPharma Inc. have launched a drug discovery collaborationagreement aimed at identifying small-molecule lead compounds to target chronicblood-based diseases. Specific diseases to be explored in the joint venturewere not disclosed.
The joint agreement, announced March 5, calls for Array todevelop assays and screen its proprietary lead generation library of 300,000small molecules to identify both active site and allosteric modulators ofcertain Global Blood targets. Array's library allows for rapid hit confirmationand subsequent lead optimization.
Array's major focus centers on leukemia, while Global Bloodis 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 15million worldwide.
"We look forward to deploying our drug discovery platformand sharing our expertise with companies like Global Blood," Kevin Koch,Array's president and chief scientific officer, stated in a news release. "Ourmutual goal is to accelerate the drug discovery and development process bycombining Global Blood's expertise in disease biology and computationallysupported medicinal chemistry with Array's established drug discoveryplatform."
SCD is one of the earliest, rare genetic diseases to bedefined on a molecular basis. It is caused by a single mutation that alters theoxygen transport protein hemoglobin and results in the "sickling"—or change toa crescent shape—of red blood cells. SCD has very limited treatment options,and there are essentially no therapies that directly address the underlyingmechanism of the disease.
Global Blood was founded to "revolutionize the treatment ofsevere, chronic diseases of the blood, and is applying class-leading approachesto drug discovery in order to develop entirely new therapies for diseases withlimited treatment options today," says Brian W. Metcalf, the company's chiefscientific officer.
"Global Blood Therapeutics has previously disclosed itsprogram focused on modulating hemoglobin in order to ameliorate sickle celldisease, and this program is progressing well," Metcalf tells ddn. "The collaboration between Global Blood and Array isfocused on multiple blood-based diseases, but specific indications and targetshave not been disclosed."
Global Blood's lead program "is developing oral smallmolecules that directly engage the altered form of hemoglobin in patients withSCD and modulate its shape in order to overcome the adverse effects of theunderlying mutation by normalizing the function of the this essential protein,"Metcalf says. "Such a drug is intended to be used chronically to reduce orprevent the chronic manifestations of SCD, thus shifting the disease from thecurrent treatment paradigm focused on episodic, acute intervention toward along-term paradigm with greater benefits for patients."
It was "through the relationships of the company's foundersand key investor, Third Rock Ventures LLC, that Global Blood and Array formed amultitarget collaboration to identify small-molecule lead compounds," Metcalfsays.
Third Rock Ventures, a venture capital firm with offices inBoston and San Francisco, provided $40.7 million Series A financing for theformation 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 withexperience treating sickle-cell patients.
SCD has gone years without a breakthrough commercialtreatment. Most of today's SCD treatments target symptoms of the disease—namelysevere 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," saysGoldsmith, who treated SCD patients during his training and as part of thefaculty of the University of California, San Francisco. "It was not a pleasantexperience … because the impact we had was modest and responsive to an acutecrisis. When we discharged somebody, we knew they would be back."
