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Dual-Specific R-Protein as an Anti-Resorptive Treatment
for Bone-Related Disorders


Osteoporosis (OP) is a common chronic skeletal disorder in aging individuals. Despite the progress made in this market, there is still a great demand for safer and more specific drugs.  Excessive bone resorption by osteoclasts is central to the pathogenesis of OP and other bone diseases. Thus, inhibition of osteoclast activity is a desired outcome in the treatment of bone and bone-related disorders. However, a complete shutdown of resorption by current drugs and uncontrolled duration of activity increases the risk for hypocalcemia, atypical fractures and osteonecrosis of the jaw limiting their utilization and decreasing patient’s compliance to their administration.

The combined expression of M-CSF receptor c-FMS and αvβ3 integrin is unique to osteoclasts and signaling through these receptors is essential to organize the osteoclast cytoskeleton elements essential for its resorption machinery. Studies in animal models demonstrated that interfering with signaling through these receptors. inhibits resorption but enables bone formation to go on. 


The Technology

A new generation of bispecific proteins based on the natural ligand M-CSF as a scaffold to engineer novel c-fms/avb3 integrin antagonists (dual specific antagonists), with the improved properties required for their application as anti-resorptive drugs in bone diseases and osteoporosis therapy.  Current results demonstrated effective inhibition of osteoclast differentiation with the dual specific antagonists compared to a variant that targets c-fms alone. Additionally, the product extensively downgrades bone resorption while preserving bone formation in ovariectomized female mouse osteoporosis model.



  • A fresh approach with a novel mode of action for bone diseases 
  • The drug is produced in yeast which enables high production yield in a relatively low price
  • Drug with improved efficacy and specificity accumulate in bones and no other organ due to targeting cells expressing both receptors
  • The drug is based on a small protein natural protein attached to human serum albumin enabling flexible control of the compound concentration and retention
  • Targeting resorption while preserving bone formation, decrease side treatment effects and enable prolong treatment duration and combination drug with bone promoting drugs (Anabolic drugs)



Patent Status

PCT application was file on August 18th, 2018, under the application number PCT/IL2017/050921. National Phase in US, EU, Canada, Australia, China and Hong Kong




Licensing out for further development



Principal Investigators

Prof. Niv Papo, NIBN and the Department of Biotechnology Engineering and Dr. Noam Levaot, Department of Physiology and Cell Biology, Ben-Gurion University of the Negev, Israel