The osteoporosis market is still in demand for new therapeutics due to the lack of safe orally available bone building drugs. Currently, parathyroid hormone (PTH;FORTEOTM) and its analogs are the only bone building therapies available yet they capture only 8% of the osteoporosis market due to significant dosing and safety limitations. OsteoGeneX is developing the first-in-class orally available therapeutic that target the new validated bone building protein sclerostin (SOST gene) for the treatment of osteoporosis and related bone disorders. Using proteomic approaches Dr. Elies and Krumlauf discovered and patented sclerostin's mechanism of action (sclerostin binds to LRP to inhibit the Wnt pathway;Issued patent 11/985,836, herein attached). Dr. Ellies has over two decades of expertise on the role of Wnt in bone and her involvement in the development of sclerostin blocking antibodies has enriched her skills to now focus on developing small molecule sclerostin inhibitor therapeutics, as opposed to large bio-molecules, i.e. antibodies and proteins, at OsteoGeneX. Dr. Ellies and her team have identified lead candidates functioning to inhibit sclerostin action on the Wnt pathway. In 2008, OsteoGeneX was awarded a SBIR Phase II from NIH/NIAMS to further develop the Phase I concept to identify the efficacious dosing of validated lead candidates. OsteoGeneX has successfully found that three structurally distinct lead candidates are efficacious at building new bone in vivo. OsteoGeneX's strategy involves an early emphasis on drug safety to reduce lead/drug atrition later in the clinical development process. In so doing, we are now taking the next step in drug development looking to identify the active functional core (pharmacophore) of three leads to allow us to then refine a lead compound that has an increased potency and decreased off-target effects (toxicity). The purpose of this SBIR application is to identify the sclerostin protein binding residues that our sclerostin small molecules interact with to enable the functional inhibition of sclerostin function and increase in bone density. Knowing the binding site will help facilitate efforts to develop and refine a safer more potent therapy to build bone for osteoporosis. At the completion of these proposed Phase I studies, OGXTM wil have selected a more potent and safe lead candidate and be primed to start preclinical efficacy studies. Once successful at demonstrating efficacy, then we would engage the FDA for an IND guidance meeting to discuss our IND strategy.
The osteoporosis market is still in demand for new therapeutics due to the lack of safe orally available bone building drugs. Currently, parathyroid hormone (PTH;FORTEOTM) and its analogs are the only bone building therapies available yet capture only 8% of the osteoporosis market due to significant dosing and safety limitations. To this end and with a lifetime use limit of 24 months, FORTEO is administered by daily subcutaneous injections and carries an FDA black box warning due to the risk of osteosarcoma. Due to the risks and limitations associated with the only bone-building option currently available, bone-loss inhibitors (biphosphonates, Fosamax(R)) capture 92% of this billion-dollar market. Of the available bone-loss inhibitor therapies and notwithstanding inconvenient dosing regimens that alleviate erosion of the esophagus, these therapies may cause osteoneicrosis of the jaw preventing any future dental work, higher frequency of atrial fibrillation, and more recently, fractures, the bisphophonate class constitutes 68% of the market share.. Clearly, there is a substantial unmet medical need for new, safe and orally available bone-building therapies. OsteoGeneX (OGX) is developing orally available first-in-class small molecules that have safety and dosing advantages over the only other bone-building therapy on the market, using the most specific bone building target available, sclerostin, which has been validated by Amgen. OGXTM bone building products will be used to treat all low bone mass conditions, and other bone-building needs (i.e. in spinal fusions, fracture repair, prosthetic anchoring). Ultimately, the useof OGXTM will result in decreased medical expenses and burden by decreasing fracture incidence thereby leading to increased social benefit as quality of life will be enhanced.