BioCryst Pharmaceuticals, Inc. announced that it has advanced a program exploring activin receptor-like kinase-2 (ALK2) inhibitors for treatment of Fibrodysplasia Ossificans Progressiva (FOP). Investigational New Drug Application (IND) enabling nonclinical development of optimized lead candidates BCX9250 and BCX9499 has been initiated with the goal of progressing to Phase 1 clinical trials in the first half of 2019. FOP is a very rare disease that affects approximately 1 in 2 million people worldwide. In patients with FOP, minor trauma can result in rapid development of painful inflammatory masses. These progress over several weeks resulting in the replacement of the affected soft tissue by permanent bone masses. There is no cure, and there are no approved treatments for FOP. ALK2 enzyme is a part of the normal signaling pathway for bone formation and responds to binding its specific ligands (bone morphogenic proteins, BMPs), by stimulating normal bone growth and renewal in healthy children and adults. Specific activating mutations of the ALK2 gene are seen in all cases of FOP. An activating mutation in ALK2 is necessary for the disease to occur, making the ALK2 kinase an ideal drug target for treatment of FOP with an ALK2 kinase inhibitor. The goal of the ALK2 inhibitor project at BioCryst is to discover and develop orally administered kinase inhibitor drug candidates that are able to slow or prevent the progressive formation of bone in soft tissues, also known as heterotopic ossification (HO). The two lead candidate molecules dramatically reduced HO in an experimental model of ALK2-driven HO in laboratory rats, with up to 89 percent reduction in volume of HO compared to controls.