New NIH Grant to Fund Exciting Osteogenesis Drug

Numerate, Inc., based in San Bruno, California, has received a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH).

The funds will be utilized to expand drug options for orthopedic surgery patients. The project is titled, “EZH2 inhibitors as endoprosthetic device coatings that induce osteogenesis and promote implant osseointegration.”

Uwe Klein, Ph.D., vice president of Biology at Numerate, is the principal investigator with co-investigator Andre J. van Wijnen, Ph.D., professor of Biochemistry and Molecular Biology, and Orthopedic Surgery at the Mayo Clinic.

Dr. Klein told OTW, “The idea for this project stems from scientific discussions between us (Numerate) and Dr. Andre van Wijnen at Mayo Clinic. Dr. van Wijnen has discovered a key role of the epigenetic enzyme EZH2 in regulating differentiation of mesenchymal stem cells to bone forming osteoblasts.”

“He has demonstrated with prototypical tool compounds that inhibition of EZH2 can stimulate bone formation. EZH2 inhibitors that are currently in clinical development for oncology indications are not suitable for chronic oral administration due to their substantial systemic toxicity and myelosuppression.”

“Together we conceived the idea of a locally delivered compound, which when included in the surface coating of an endoprosthetic device would stimulate bone formation at the device/bone interface and improve device osseointegration.”

“The research plan for the SBIR [Small Business Innovation Research] funded program takes advantage of the synergies that exist between Numerate and Dr. van Wijnen’s laboratory.”

“Numerate’s AI [artificial intelligence] driven drug discovery platform and expertise in small-molecule drug discovery is ideally suited to identify compounds with the desired pharmacological and physicochemical properties, while Dr. van Wijnen’s laboratory brings deep expertise in bone biology, and has the experience and know-how to conduct complex cell-based in vitro and in vivo biological studies to provide proof of our hypothesis.”

“Dr. van Wijnen’s work will include coating of surrogate titanium disks and demonstration of differentiation of mesenchymal stem cells grown on the disk surface coated with test compounds. Within the research plan, we also involve a contract research laboratory, which will provide biochemical data to confirm potency and selectivity of the compounds identified using Numerate’s discovery platform.”

“If successful, this program will result in the discovery and development of novel drug/device combinations, which would be easy to prepare and use in the operating room, would provide safe treatment options with minimal safety and tolerability issues, and should substantially improve short- and long-term success rate of endoprosthetic device surgeries. Especially in elderly patients with bone disorders such as osteoporosis or arthrosis who have poor bone regenerative potential, such a strategy should result in better osseointegration, lower risk for aseptic loosening and a reduced number of revision surgeries.”