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Jun 18, 2013

NCATS Awards $12.7M for Nine Drug Repurposing Projects

  • NIH’s National Center for Advancing Translational Sciences (NCATS) awarded a total $12.7 million to nine academic research groups toward repurposing seven of 58 compounds made available by pharma giants through the agency-industry Discovering New Therapeutic Uses for Existing Molecules pilot program.

    The nine—chosen from 160 applicants—are slated to receive between $500,000 and around $3 million over two years to study whether and how the seven compounds might be redeveloped into new treatments in eight disease areas—including NIH priorities such as Alzheimer’s disease and alcohol abuse.

    “What this program is doing is to test a really new model for establishing pharma-academia collaborations, and doing it in a community-wide way,” NCATS Director Christopher P. Austin, M.D., said during a conference call with reporters.

    NIH did not disclose some of the seven compounds pending completion of provisional patent paperwork for their new indications -- though the agency said after the phone conference that two of the compounds were each involved in two studies. One of those comes from Sanofi, while the other is among a pair of AstraZeneca compounds being studied in three projects:

    • Saracatinib (AZD0530), an Src tyrosine kinase inhibitor, will be explored as a potential Alzheimer’s therapy by Yale University researchers Stephen M. Strittmatter, M.D., Ph.D., Haakon Berge Nygaard, M.D., Ph.D., and Christopher H. Van Dyck, M.D. Activation of Fyn kinase in a mouse model impaired memory and reduced signals between brain cells, but removing it stopped these symptoms.
    • Saracatinib will also be examined by N. Tony Eissa, M.D., of Baylor College of Medicine as a potential Lymphangioleiomyomatosis (LAM) treatment. He will assess whether Src kinase is active in LAM cells, its importance in cells’ growth and ability to invade tissues – and whether blocking Src activity with the compound is safe and can reduce how LAM cells grow and spread.
    • Zibotentan (ZD4054) will be studied by University of Virginia researcher Brian H. Annex, M.D., for patients with symptomatic Peripheral Artery Disease (PAD). He will test zibotentan’s ability to improve blood flow in PAD patients’ legs, and help patients walk further and longer.

    Two Schizophrenia Projects

    Eli Lilly’s selective estrogen receptor beta agonist LY500307 will be studied by Alan Breier, M.D., of Indiana University for safety and ability to relieve symptoms in patients with schizophrenia.

    Also being assessed for schizophrenia is a Pfizer GlyT1 inhibitor under study by John H. Krystal, M.D., of Yale University for reducing abnormal function of the NMDAR receptor, a contributor to cognitive defects associated with the disease.

    Another undisclosed Pfizer compound will be examined by Fatemeh Akhlaghi, Pharm.D., Ph.D., of the University of Rhode Island and Lorenzo Leggio, M.D., Ph.D., from NIH’s National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse. The researchers will test whether a ghrelin inhibitor safely reduces alcohol dependence, following animal and human tests in which blocking ghrelin activity showed promise.

    NIH will also fund research by Kathryn R. Wagner, M.D., Ph.D., of Kennedy Krieger Institute, and Stanley C. Froehner, Ph.D., of the University of Washington for investigations on an undisclosed Sanofi compound against Duchenne muscular dystrophy (DMD). The researchers will assess the compound’s effectiveness in a mouse MD model and safety in young animals, followed by testing for safety and ideal dose level in DMD patients.

    Mayo Clinic researchers Jordan D. Miller, Ph.D., Maurice Enriquez-Sarano, M.D., and Hartzell V. Schaff, M.D., will test the same undisclosed Sanofi compound for safety and proof of concept in slowing progression of stenosis in humans, with potential to reduce death and illness from progression of calcific aortic valve disease.

    Finally, Darlene H. Brunzell, Ph.D., of Virginia Commonwealth University and Kenneth Alan Perkins, Ph.D., of University of Pittsburgh will study an undisclosed compound from Johnson & Johnson’s Janssen Research & Development unit as a tobacco-cessation treatment through studies in rodents and clinical trials.

    Janssen, Sanofi, Pfizer, Lilly, and AstraZeneca are five of eight pharma giants contributing compounds to the pilot program. The others were AbbVie, Bristol-Myers Squibb, and GlaxoSmithKline.

    This story has been updated to include additional, late-breaking details from NIH on the compounds being studied.


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