Thursday, May 15, 2025
5/15/2025
Oral delivered bone building therapy for osteoporosis - DESCRIPTION (provided by applicant): 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.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).