Third Rock Ventures reported the launch of Fulcrum Therapeutics, which works on unlocking gene control mechanisms to develop small-molecule therapies. Fulcrum expects to discover and develop small molecules that modulate the on/off control mechanisms that regulate genes.

Officials at Fulcrum, which was established with $55 million in Series A financing, say the firm will develop a pipeline across therapeutic areas, spearheaded by two initial programs in genetic diseases. The company’s president and CEO, Robert J. Gould, Ph.D., is the former president and CEO of Epizyme,

“One of the single most important biologic breakthroughs of the last decade has been the unraveling of gene regulation at a molecular level. For more than a decade we have understood the genetic code–the genome. Now that we are unraveling the way these genes are regulated and put to work in biology, there is an unprecedented opportunity for drug development,” Dr. Gould said.

Fulcrum models gene regulation in disease tissue using patient cells that are either donated through tissue biopsy or derived from skin cells using the technology of induced pluripotent stem cells. It uses screening tools such as CRISPR/Cas9 and chemical probe libraries to dissect gene regulatory mechanisms in cellular models of diseases. These discoveries are brought together with publicly available gene regulatory data to create genome-wide maps of gene regulation that enable identification of drug targets for the activation or repression of disease genes. The combination of patient-derived cells, screening tools, and genome-wide databases enables Fulcrum’s product engine, continued Dr. Gould.

The company believes there is long-term potential to address complex genetic diseases through its approach. The early focus of Fulcrum’s product engine is on two severe genetic diseases—fragile X syndrome (FXS) and a form of muscular dystrophy called facioscapulohumeral muscular dystrophy (FSHD). Each disease arises from a single gene mutation that creates an error in gene regulation. In the case of fragile X, the silencing of the FMR1 gene eliminates the cell’s ability to make a protein needed for brain function. In FSHD, the precipitating event is the activation of a gene called DUX4 that should be silent in adulthood. This activation leads to muscle wasting as cells die.

Other genetic diseases that can be explored with Fulcrum’s robust product engine include other neurologic disorders, skeletal muscular disorders, and cardiac muscular disease. 

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