LEXINGTON, MA, USA I September 11, 2020 I Keros Therapeutics, Inc. (“Keros” or the “Company”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today announced results from preclinical studies of KER-012 at the American Society for Bone and Mineral Research (ASBMR) 2020 Annual Meeting Virtual Event held September 11-15, 2020.
In Preclinical Studies, KER-012 Increased Trabecular Bone by Reducing Bone Catabolism and Enhancing Anabolism
- KER-012, A Novel Activin Receptor Type II Ligand Trap, Increases Bone in Mice Via a Unique Mechanism of Action – Presentation Number: P-656
TGF-β superfamily ligands, including activin A and B, are negative regulators of bone remodeling, suppressing bone growth. KER-012 is a modified activin receptor type II ligand trap designed to bind to and inhibit activins and SMAD 2/3 signaling. In adult male mice, administration of KER-012 (20 mg/kg twice weekly for 5 weeks) resulted in the following statistically significant changes relative to vehicle treatment:
- Increased trabecular bone volume (82.0%; p<0.001), higher trabecular bone volume fraction (78.3%; <0.001) and increased trabecular number (33.5%; p<0.01).
- Increased trabecular thickness (28.8%; p<0.01) and reduced trabecular separation (-27.2%; p<0.001).
Enhanced bone anabolism was demonstrated through:
- Increased (i) trabecular mineralizing surface (+63.4%; p<0.01), (ii) trabecular mineral apposition rate (+29.9%; p<0.05) and (iii) trabecular bone formation rate (+107.7%; p<0.01), as well as a trend towards increased osteoblast number (+29.0%; NS).
Reductions in bone catabolism were evidenced by:
- Reduced (i) trabecular eroded surface (-42.2%; p<0.001) and (ii) trabecular osteoclast number (-45.8%; p<0.01).
The observed increase in osteoblast/osteoclast ratio (+125.0%; p<0.01) is potentially indicative of the dual mechanism of increased anabolism and decreased catabolism.
“Taken together, we believe the results from these preclinical studies provide further support of our hypothesis that KER-012 acts through a differentiated mechanism to increase trabecular bone by reducing bone resorption and enhancing formation,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. “We believe that the mechanism of action of KER-012 represents a unique opportunity to potentially treat a number of conditions where bone loss is an issue, such as osteoporosis and cancer-induced bone loss.”
About KER-012
KER-012 is designed to bind to and inhibit the signaling of transforming growth factor-beta ligands, including activin A and activin B, which are key regulators of bone remodeling that act to suppress bone growth. KER-012 is being developed for the treatment of disorders associated with bone loss, such as osteogenesis imperfecta and osteoporosis, and for the treatment of pulmonary arterial hypertension.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematologic and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the Transforming Growth Factor-Beta family of proteins, which are master regulators of red blood cell and platelet production as well as of the growth, repair and maintenance of muscle and bone. Keros’ lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes and in patients with myelofibrosis. Keros’ lead small molecule product candidate, KER-047, is being developed for the treatment of anemia resulting from elevated levels of hepcidin, the key regulator of iron absorption and recycling, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros’ third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
SOURCE: Keros Therapeutics
Post Views: 25
LEXINGTON, MA, USA I September 11, 2020 I Keros Therapeutics, Inc. (“Keros” or the “Company”) (Nasdaq: KROS), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematological and musculoskeletal disorders with high unmet medical need, today announced results from preclinical studies of KER-012 at the American Society for Bone and Mineral Research (ASBMR) 2020 Annual Meeting Virtual Event held September 11-15, 2020.
In Preclinical Studies, KER-012 Increased Trabecular Bone by Reducing Bone Catabolism and Enhancing Anabolism
- KER-012, A Novel Activin Receptor Type II Ligand Trap, Increases Bone in Mice Via a Unique Mechanism of Action – Presentation Number: P-656
TGF-β superfamily ligands, including activin A and B, are negative regulators of bone remodeling, suppressing bone growth. KER-012 is a modified activin receptor type II ligand trap designed to bind to and inhibit activins and SMAD 2/3 signaling. In adult male mice, administration of KER-012 (20 mg/kg twice weekly for 5 weeks) resulted in the following statistically significant changes relative to vehicle treatment:
- Increased trabecular bone volume (82.0%; p<0.001), higher trabecular bone volume fraction (78.3%; <0.001) and increased trabecular number (33.5%; p<0.01).
- Increased trabecular thickness (28.8%; p<0.01) and reduced trabecular separation (-27.2%; p<0.001).
Enhanced bone anabolism was demonstrated through:
- Increased (i) trabecular mineralizing surface (+63.4%; p<0.01), (ii) trabecular mineral apposition rate (+29.9%; p<0.05) and (iii) trabecular bone formation rate (+107.7%; p<0.01), as well as a trend towards increased osteoblast number (+29.0%; NS).
Reductions in bone catabolism were evidenced by:
- Reduced (i) trabecular eroded surface (-42.2%; p<0.001) and (ii) trabecular osteoclast number (-45.8%; p<0.01).
The observed increase in osteoblast/osteoclast ratio (+125.0%; p<0.01) is potentially indicative of the dual mechanism of increased anabolism and decreased catabolism.
“Taken together, we believe the results from these preclinical studies provide further support of our hypothesis that KER-012 acts through a differentiated mechanism to increase trabecular bone by reducing bone resorption and enhancing formation,” said Jasbir S. Seehra, Ph.D., President and Chief Executive Officer of Keros. “We believe that the mechanism of action of KER-012 represents a unique opportunity to potentially treat a number of conditions where bone loss is an issue, such as osteoporosis and cancer-induced bone loss.”
About KER-012
KER-012 is designed to bind to and inhibit the signaling of transforming growth factor-beta ligands, including activin A and activin B, which are key regulators of bone remodeling that act to suppress bone growth. KER-012 is being developed for the treatment of disorders associated with bone loss, such as osteogenesis imperfecta and osteoporosis, and for the treatment of pulmonary arterial hypertension.
About Keros Therapeutics, Inc.
Keros is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of novel treatments for patients suffering from hematologic and musculoskeletal disorders with high unmet medical need. Keros is a leader in understanding the role of the Transforming Growth Factor-Beta family of proteins, which are master regulators of red blood cell and platelet production as well as of the growth, repair and maintenance of muscle and bone. Keros’ lead protein therapeutic product candidate, KER-050, is being developed for the treatment of low blood cell counts, or cytopenias, including anemia and thrombocytopenia, in patients with myelodysplastic syndromes and in patients with myelofibrosis. Keros’ lead small molecule product candidate, KER-047, is being developed for the treatment of anemia resulting from elevated levels of hepcidin, the key regulator of iron absorption and recycling, as well as for the treatment of fibrodysplasia ossificans progressiva. Keros’ third product candidate, KER-012, is being developed for the treatment of disorders associated with bone loss, such as osteoporosis and osteogenesis imperfecta, and for the treatment of pulmonary arterial hypertension.
SOURCE: Keros Therapeutics
Post Views: 25
