I-HBD1 Peptide Program for bone diseases
|Company||Alize Pharma III SAS|
|Program||I-HBD1, peptide with bone anabolic properties for the treatment of rare bone diseases and osteoporosis|
|Stage of development||Lead optimization|
Sofimac Partners (Emergence Innovation 1)
Sham Innovation Santé
Crédit Agricole Création
The I-HBD1 program aims to optimize and develop a new peptide derived from a fragment of a physiological protein, called IGFBP-2 (Insulin-like Growth Factor Binding Protein-2), as a new bone anabolic agent for the treatment of rare bone diseases and osteoporosis.
Scientific work led by Drs David Clemmons from University of North Carolina at Chapel Hill and Dr Clifford Rosen from the University of Maine has established that IGFBP2 plays a key physiological role for the differentiation of osteoblasts, the cells responsible for bone formation. I-HBD1, a short peptide fragment derived from IGFBP-2, replicates IGFBP-2 effects on bone and has shown strong bone formation potency in ovariectomized rats and mice. It is intended to be developed as a bone anabolic agent in osteoporosis and/or some rare metabolic diseases associated with impaired bone formation such as osteogenesis imperfecta.
The I-HBD1 project is being conducted in collaboration with New Paradigm Therapeutics, a spin-off company of the University of North Carolina at Chapel Hill founded by Professor David Clemmons.
The International Osteoporosis Foundation estimates that osteoporosis affects more than 200 million people worldwide and causes almost 9 million fractures each year. The global market for osteoporosis drugs was estimated at over $8.3 billion in 2014, with significant growth expected in the coming years. The current treatments are mostly anti-resorptive therapies, so there is an unmet need for safer, more cost-effective anabolic therapies that are able to build new bone for these patients.
Xi G, Wai C, Abribat T, Delale T, Demambro V, Rosen CJ and Clemmons DR: A unique peptide containing the heparin binding domain of IGFBP-2 increases bone mass in OVX rats. ASBMR (2016)
Xi G, Rosen CJ, Clemmons DR: IGF-I and IGFBP-2 Stimulate AMPK Activation and Autophagy, Which Are Required for Osteoblast Differentiation. Endocrinology. 157(1):268-81 (2016)
- Xi G, Wai C, DeMambro V, Rosen CJ, Clemmons DR. IGFBP-2 Directly Stimulates Osteoblast Differentiation. J Bone Miner Res. 2014 Nov; 29(11):2427-38
- Xi G, Solum MA, Wai C, Maile LA, Rosen CJ, Clemmons DR. The Heparin-Binding Domains of IGFBP-2 Mediate Its Inhibitory Effect on Preadipocyte Differentiation and Fat Development in Male Mice. Endocrinology. 2013 Nov;154(11):4146-57.
- Shen X, Xi G, Maile LA, Wai C, Rosen CJ, Clemmons DR. Insulin-like growth factor (IGF) binding protein 2 functions coordinately with receptor protein tyrosine phosphatase β and the IGF-I receptor to regulate IGF-I-stimulated signaling. Mol Cell Biol. 2012 Oct;32(20):4116-30.
- DeMambro VE, Maile L, Wai C, Kawai M, Cascella T, Rosen CJ, Clemmons D. Insulin-like growth factor-binding protein-2 is required for osteoclast differentiation. J Bone Miner Res. 2012 Feb;27(2):390-400.
- Kawai M, Breggia AC, DeMambro VE, Shen X, Canalis E, Bouxsein ML, Beamer WG, Clemmons DR, Rosen CJ. The heparin-binding domain of IGFBP-2 has insulin-like growth factor binding-independent biologic activity in the growing skeleton. J Biol Chem. 2011 Apr 22;286(16):14670-80.
- DeMambro VE, Clemmons DR, Horton LG, Bouxsein ML, Wood TL, Beamer WG, Canalis E, Rosen CJ. Gender-specific changes in bone turnover and skeletal architecture in IGFBP-2-null mice. Endocrinology. 2008 May;149(5):2051-61.
- Shen X, Xi G, Wai C, Clemmons DR: The Coordinate Cellular Response to Insulin-like Growth Factor-I (IGF-I) and Insulin-like Growth Factor-binding Protein-2 (IGFBP-2) Is Regulated through Vimentin Binding to Receptor Tyrosine Phosphatase β (RPTPβ). J Biol Chem. 2015 May 1;290(18):11578-90.