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National Institutes of Health Awards Grant to Numerate to Develop Compounds that Enhance Bone Integration of Orthopedic Devices

Numerate,Inc.
Posted on: 15 Nov 17

Numerate, Inc., a computational drug design company applying artificial intelligence (AI) at cloud scale to transform small molecule drug discovery, announced that the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH) awarded Numerate a grant to improve outcomes for patients who need an orthopedic implant surgery.

The project titled, “EZH2 inhibitors as endoprosthetic device coatings that induce osteogenesis and promote implant osseointegration” is expected to identify potential drug options that will ultimately help patients undergoing implant surgeries.

Uwe Klein, Ph.D., Vice President, Biology at Numerate, will lead the discovery efforts and serve as Principal Investigator with co-investigator Andre J. van Wijnen, Ph.D., professor of Biochemistry and Molecular Biology, and Orthopedic Surgery at the Mayo Clinic.

The project is based on work in Dr. van Wijnen’s laboratory that demonstrated a key role of the epigenetic enzyme ‘Enhancer of Zeste homolog 2’ (EZH2) in skeletal development and the differentiation of osteoblasts, the cells critical for new bone formation. Dr. van Wijnen has shown that inhibition of EZH2 results in the stimulation of new bone formation by activation of the osteogenic pathway in mesenchymal stem cells1. Surface coating of orthopedic implants used in hip and knee replacement procedures with such compounds is expected to facilitate integration of existing bone with the device. Better device/bone integration may reduce complications stemming from poor anchoring of implants and improve implant life-time, especially in patients suffering from bone disorders such as osteoporosis, arthrosis or osteopenia.

“We are pleased to receive this award from the NIH and are excited to work with Dr. van Wijnen, a renowned expert in bone biology, to build upon his work and discover an important new drug for use in a drug/device combination for orthopedic indications, addressing a significant medical need in the aging population in the United States,” said Uwe Klein, Ph.D., Vice President, Biology at Numerate.

With an aging population and increased life span, the number of patients requiring reconstructive joint surgeries or joint replacements continues to increase. Many patients undergoing arthroplasty procedures suffer from bone disorders such as osteoporosis, severe arthrosis or osteopenia, with a bony matrix that impedes firm anchoring of implants to existing bone. This results in poor implant osseointegration and aseptic loosening, and requires revision surgeries in many patients. The need and opportunity exists for new therapeutic strategies that improve bone-implant contact and device osseointegration2.

“The NIAMS funding will allow us to further explore the therapeutic utility of EZH2 inhibition to treat bone disorders,” said Dr. Andre van Wijnen. “We hope that this work will allow us to offer better treatment options for patients who need short-term augmentation of bone formation including those requiring endoprosthetic device implants.”

John Griffin, Ph.D., Chief Scientific Officer of Numerate, added, “Our AI-based drug discovery platform has the potential to accelerate the discovery and development of novel small molecule compounds with optimized properties for use in combination with a device, and with minimized systemic toxicity. We are looking forward to collaborating with Dr. van Wijnen and his team at Mayo Clinic.”

This works is being supported by the Small Business Innovation Research (SBIR) Phase I grant (1R43AR073051-01), awarded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National Institutes of Health (NIH).

About Numerate

Numerate is a privately-held computational drug design company that is transforming the discovery of new medicines that fill significant therapeutic gaps by harnessing the vast computational power of the cloud and the ever-increasing amounts of drug discovery data by applying proprietary artificial intelligence algorithms. Numerate’s drug design platform combines advances in computer science and statistics with traditional medicinal chemistry approaches to overcome major challenges in small molecule drug discovery and significantly accelerate candidate selection and optimization. Using this platform, coupled with innovative funding and partnership models, Numerate is developing a therapeutic pipeline focused on producing first-in-class candidates against emerging targets addressing major unmet medical needs in cardiovascular, metabolic and neurodegenerative disease. For more information, visit www.numerate.com.

 
1 Dudakovic et al (2016) Enhancer of Zeste Homolog 2 Inhibition Stimulates Bone Formation and Mitigates Bone Loss Caused by Ovariectomy in Skeletally Mature Mice. J Biol Chem. 291(47):24594-24606.
2 Kremers et al (2016) Clinical Factors, Disease Parameters, and Molecular Therapies Affecting Osseointegration of Orthopedic Implants. Curr Mol Biol Rep. 2(3):123-132.
 

View source version on businesswire.com: http://www.businesswire.com/news/home/20171115005391/en/

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Last updated on: 15/11/2017

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