Company’s SHAPE Platform will be used to discover small molecules that change the shape of key blood proteins.
Third Rock Ventures has formed Global Blood Therapeutics with $40.7 million in Series A financing. The company’s SHAPE Platform has the ability to identify oral, small molecule drugs that change the shapes of key blood proteins to modify their functions, enhance vital biological pathways, and drive therapeutic benefits.
The SHAPE Platform brings together advanced computational biology and protein-ligand modeling with medicinal chemistry and empiric screening capabilities focused on allosteric modulation. Global Blood Therapeutics is building a pipeline for severe, genetic blood diseases for which there are currently no effective cures and only extremely limited therapeutic options.
“Blood is one of the largest and most accessible organs and is a rich source of biologically and clinically validated targets,” remarks Mark A. Goldsmith, M.D., Ph.D., CEO of the new company and venture partner at Third Rock Ventures. “Global Blood Therapeutics aims to provide game-changing treatments for serious, genetic blood diseases that are well-understood but poorly served today by developing innovative medicines directed against clinically validated targets.
“Through our SHAPE Platform and our world-class team with a strong track record in science and drug discovery and development,” Dr. Goldsmith notes, “we are positioned to develop rapidly a new generation of safe and effective oral drugs that could truly change the treatment paradigm on behalf of patients.”
Founders of the company include Charles Homcy, M.D., and Craig Muir of Third Rock Ventures, David Phillips, Ph.D., co-founder of COR Therapeutics and Portola Pharmaceuticals, and three leading scientific researchers at the University of California, San Francisco: Matthew Jacobson, Ph.D., professor, pharmaceutical chemistry, Andrej Sali, Ph.D., professor, bioengineering and therapeutic sciences, and Jack Taunton, Ph.D., associate professor, cellular and molecular pharmacology.
Global Blood Therapeutics’ lead program focuses on sickle cell disease (SCD). It is caused by a point mutation in the hemoglobin beta chain, converting β6 glutamic acid to valine. When sickle hemoglobin (HbS) is deoxygenated, the replacement of β6 glutamic acid with valine results in a hydrophobic interaction with another hemoglobin molecule, triggering an aggregation into large polymers. The polymerization of deoxygenated HbS is the primary event in the molecular pathogenesis of SCD, resulting in a distortion of the red blood cell and a marked decrease in its ability to pass through the microvasculature. These rigid cells are responsible for the vaso-occlusive crisis that are the hallmark of the disease.
Global Blood Therapeutics is pursuing multiple drug discovery strategies for the treatment of SCD. In its lead program the company has identified small molecules that modulate the shape of HbS to a form that favors the oxygenated state. This approach may prevent the polymerization of HbS, allow the red blood cell to pass through the microvasculature, and improve the multiple pathologies associated with SCD.