Lead Structure Discovery for Neglected Diseases: Product Development Partnerships Driving Drug Discovery

13 May 2016

Jeremy N. Burrows andTakushi Kaneko

Book - Lead Generation: Methods, Strategies, and Case Studies

DOI: 10.1002/9783527677047.ch24

Photo: Pichit/Shuttershock.com

Summary

Neglected and tropical diseases, such as malaria and tuberculosis, are a huge economic and health burden on developing countries and affect a large proportion of the population globally. Despite the high unmet medical need and the size of the patient populations, there is a dearth of efficacious, well-tolerated medicines that meet the desired, current target product profiles. This is due to market failure; the incentives for a commercial pharmaceutical company to invest in drug discovery and development for neglected and tropical diseases simply do not exist. As such, in response to this, a new model of drug discovery in this sector has arisen. Product development partnerships (PDPs) have been established with disease foci that, with funding from public and private sources, are able to collaborate with academia and pharmaceutical industry worldwide, providing the necessary risk and cost sharing models that enable organizations to commit resources and expertise to find new leads, candidates, and drugs. This chapter uses two PDPs (Medicines for Malaria Venture or MMV and the Global Alliance for TB Drug Development (or TB Alliance) as case studies to review how the early drug discovery strategy for malaria and tuberculosis has undergone a renaissance in the past decade and, in particular, highlighting the unique successful approaches that are bearing fruit in a still resource-limited environment.

Neglected tropical diseases (NTDs) are those infectious parasitic, viral, and bacterial diseases that occur globally, but predominantly within the tropics. The nongovernmental organizations such as product development partnerships (PDPs) including Medicines for Malaria Venture (MMV), Drugs for Neglected Diseases Initiative (DNDi), and the Global Alliance for Tuberculosis Drug Development (GATB), have established strong drug discovery and development portfolios through collaboration with global partners and through disease-specific expertise offer an attractive model for partnership. Two fixed dose combination target product profiles (TPPs) have been defined for antimalarial drug discovery. These are TPP1 for treatment and TPP2 for chemoprotection. The majority of hit and lead generation, as well as lead optimization, strategies have focused on the asexual blood stage, that is, the stage responsible for clinical symptoms and death. This chapter describes four main antimalarial hit identification strategies.

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