āshibio is building a pipeline of innovative therapeutics to impact bone and connective tissue disorders that have no approved treatments, or where the treatment options are inadequate.
Our Pipeline
Andecaliximab
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease characterized by severe and progressive heterotopic ossification (HO) starting in early childhood and worsening with age. FOP caused by a mutation in the ACVR1/ALK2 gene, which regulates bone growth and development, with the most common mutation being R206H which is found in over 97% of individuals with FOP.
A recent publication from the lab of Dr. Frederick Kaplan at University of Pennsylvania showed that MMP9 could serve as a novel target for inhibiting heterotopic ossification in patients with FOP.
HO can also occur in the absence of a genetic mutation in conditions such as spinal cord injury, traumatic brain injury, joint replacement surgery, burns and amputations. This type of HO is often called non-genetic HO or non-hereditary HO (NHHO). Research by āshibio has shown that MMP9 could also serve as a novel target for inhibiting NHHO.
Andecaliximab is a novel antibody targeting matrix metalloprotease type 9 (MMP9). This investigational antibody has been previously tested in clinical trials for cancer and inflammatory diseases involving approximately 1000 patients. Andecaliximab, a monoclonal antibody, is a potent and specific inhibitor of MMP9. In FOP, MMP9 is a key enzyme that releases the long form of Activin-A locally in inflamed tissues as shown in the figure. Activin-A can then bind to the mutant ALK2 receptor resulting in HO formation. Studies in mouse models of FOP have shown that blocking the activity of MMP9 can significantly inhibit the formation of HO.
We are charting a path to transform care for bone and connective tissue disorders.
Vantictumab
Vantictumab is being developed for the treatment of autosomal dominant osteopetrosis type 2 (ADO2, also known as Albers-Schönberg disease), which is a genetic disorder caused by reduced function of osteoclasts. Impaired osteoclast function results in dense, brittle bone and leads to complications such as multiple fractures, poor bone healing, low blood counts (due to encroachment of the bone marrow), and nerve compression that can cause pain, deafness, and/or blindness. ADO2 results from a mutation in the chloride channel 7 (CLCN7) gene, with the most common mutation being G215R.
The Wnt pathway plays a key role in bone homeostasis. Vantictumab is a novel antibody that binds to certain Frizzled receptors and inhibits the Wnt signaling pathway. Research by āshibio scientists in collaboration with the laboratory of Dr. Michael Econs at University of Indiana School of Medicine has shown that vantictumab can rescue the bone phenotype in a mouse model of ADO2.
Vantictumab, an investigational antibody, has previously been tested in clinical trials for cancer involving approximately 100 patients. As shown in the figure, vantictumab binds to selected Frizzled receptors and increases osteoclast activity thereby restoring the bone phenotype in a mouse model of ADO2.
