Identification of lead compounds as novel anti‐TB agents
  • Awarded Year
    2015
  • Awarded Amount
    $908,231
  • Disease
    Tuberculosis
  • Intervention
    Drug
  • Development Stage
    Lead Identification
  • Collaboration Partners
    Daiichi Sankyo, Inc., The Global Alliance for TB Drug Development

Introduction and Background of the Project

Most of TB drugs currently in use were discovered 40-50 years ago and little has changed over this period.  Even for cases of drug-sensitive TB patients, it takes on average 6 months of treatment with multiple drugs a day.  In the case of drug-resistant TB, the situation is much worse, requiring daily injections for 6 months and continued medication for at least 18 months, all the while using ineffective and toxic drugs. Therefore, new TB drugs are urgently needed to shorten the treatment duration and to combat drug-resistant strains of Mycobacterium tuberculosis (M tb), the causative agent of TB.  

The GHIT supported project with Daiichi-Sankyo, the University of Illinois at Chicago (UIC), and TB Alliance screened 70,000 unique compounds from Daiichi-Sankyo’s libraries in the laboratory of Dr. Scott Franzblau at UIC for their ability to kill M tb in culture.  The selection of three hits (compounds active against M tb) and proposed research to develop the series was made in a close collaboration among the participating organizations.  The synthesis of new analogues will be carried out by Daiichi-Sankyo in India and their activity against M tb will be assessed by UIC.  The expectation is to complete the hit-to-lead process within 21 months and identify a drug lead at the end of this period to be further developed.

How can your partnership (project) address global health challenges?

TB causes approximately 1.5 million deaths per year globally, or three deaths every minute. One of the challenges of current TB care is the duration of therapy and lack of new treatments that are effective against drug-resistant strains.  This collaboration between Daiichi-Sankyo, GHIT, UIC and TB Alliance is uniquely poised to deliver novel drug candidates to combat TB.  TB Alliance is a product development partnership (PDP), a type of organization that focuses R&D activities on areas where there is a market failure due to health needs but insufficient profits to draw private sector investments. This three-way collaboration allows sharing the know-how of a prominent pharmaceutical company and the vast network of TB Alliance partners with academic researchers throughout the world. It is designed to maximize the impact of research in TB a severely under-resourced therapeutic area. The end result of this collaboration is expected to be a drug lead that can be further optimized for efficacy and safety.

What sort of innovation are you bringing in your project?

The 70,000 compounds screened to generate the original hits are designed and synthesized by Daiichi-Sankyo scientists based on their concept of common pharmacophores (Pharma Space Library).  The compounds are unique to Daiichi-Sankyo and had not been screened against M tb until this GHIT-sponsored screen.  The hits are expected to be drug-like and easily amenable to further synthesis of analogues.  The hits were checked against other hits in the literature from other organizations and they are indeed unique.  The design of new analogues and synthesis will be carried out by the chemists at Daiichi-Sankyo India Pharma who have prior experience of working in the TB field. It is also significant that this research will be conducted in India where the estimated number of TB patients is 2.6 million for 2013, the largest epidemic country in the world (see reference 1).  

Others (including references if necessary)

Reference  1 “Global Tuberculosis Control 2014, WHO, Geneva, 2014 www.who.int/tb/publications/global_report