Lead generation

Novartis miniportfolio

Lead optimisation

Project Leader: Dr Bryan Yeung, Novartis Institute of Tropical Diseases, Singapore

Partners: Genomics Institute of the Novartis Research Foundation USA; Novartis Natural Products Research, Switzerland; Swiss Tropical and Public Health Institute, Switzerland; BPRC, the Netherlands and Wellcome Trust, UK

MMV Project Director: Dr Brice Campo

This collaboration is focused on discovering new molecules that could become a radical cure for P. vivax malaria. With this goal in mind the team is developing new biological assays to help identify such molecules.

Miniportfolios

Early discovery projects – by their very nature – have high rates of attrition. While a specific project might fail, the resources, including expertise and equipment remain nonetheless valuable. In response to this, MMV pioneered the miniportfolio model. The model assures flexibility in allocation of resources – established between MMV and a Pharmaceutical or Biotechnology partner – from one project to another. In this way, resources are utilized as efficiently as possible.

Our partners provide drug discovery expertise, and many further contributions both in-kind and financial. Each miniportfolio agreement has allowed us access to new compound libraries for high content screening. And each library provides us with an immense treasure trove of new starting points for medicinal chemistry to feed the entire pipeline.

GlaxoSmithKline miniportfolio

Lead optimisation

Project Leader: Dr Javier Francisco Gamo-Benito, GlaxoSmithKline

MMV Project Director: Dr Paul Willis

The GSK/MMV collaboration uses in vitro and in vivo screening strategies to identify compounds with the potential for rapid- and long-duration action against the blood stages of both P. falciparum and P. vivax malaria. The collaboration also seeks to identify molecules that target mature gametocytes, and thus have potential to block transmission of malaria to the mosquito vector.

Miniportfolios

Early discovery projects – by their very nature – have high rates of attrition. While a specific project might fail, the resources, including expertise and equipment remain nonetheless valuable. In response to this, MMV pioneered the miniportfolio model. The model assures flexibility in allocation of resources – established between MMV and a Pharmaceutical or Biotechnology partner – from one project to another. In this way, resources are utilized as efficiently as possible.

Our partners provide drug discovery expertise, and many further contributions both in-kind and financial. Each miniportfolio agreement has allowed us access to new compound libraries for high content screening. And each library provides us with an immense treasure trove of new starting points for medicinal chemistry to feed the entire pipeline.

Sanofi miniportfolio

Lead optimisation

Project Leaders: Dr Laurent Fraisse & Dr Alain Pellet, Sanofi, Toulouse, France

Partners: Swiss TPH, Basel, Switzerland and Syngene, Bangalore, India

MMV Project Director: Dr Didier Leroy

The project team are currently working on 800 orthologues (compounds known to be active against targets in man that exist in the parasite), screened against the non-blood stages of the parasite’s lifecycle. Compounds that have been found to be active against the sexual and liver stages of Plasmodium are being characterized further to define the most promising new medicinal chemistry starting points aligned with our Target Candidates Profiles for malaria eradication. Ideally, these molecules will have the potential to block transmission and stop the relapse of P. vivax malaria. In 2014, other Sanofi libraries will be screened on different stages of P. falciparum to offer new chemical starting points.

Miniportfolios

Early discovery projects – by their very nature – have high rates of attrition. While a specific project might fail, the resources, including expertise and equipment remain nonetheless valuable. In response to this, MMV pioneered the miniportfolio model. The model assures flexibility in allocation of resources – established between MMV and a Pharmaceutical or Biotechnology partner – from one project to another. In this way, resources are utilized as efficiently as possible.

Our partners provide drug discovery expertise, and many further contributions both in-kind and financial. Each miniportfolio agreement has allowed us access to new compound libraries for high content screening. And each library provides us with an immense treasure trove of new starting points for medicinal chemistry to feed the entire pipeline.

AstraZeneca miniportfolio

Lead optimisation

Project Leader: Dr Shridhar Narayanan, AstraZeneca India, Bangalore

MMV Project Director: Dr Brice Campo

This collaboration allows MMV access to AstraZeneca’s extensive compound library in order to identify promising compounds with the potential to treat malaria. To date, 500,000 compounds from AstraZeneca’s unique library have been screened for activity against P. falciparum, the most lethal of malaria parasites.

Promising compounds have been identified through the screening process that represent potential starting points for antimalarial drug discovery projects. These compounds will be progressed through a discovery cascade at AstraZeneca’s R&D facility in Bangalore, India, with the aim of identifying suitable candidates for clinical testing.

Miniportfolios

Early discovery projects – by their very nature – have high rates of attrition. While a specific project might fail, the resources, including expertise and equipment remain nonetheless valuable. In response to this, MMV pioneered the miniportfolio model. The model assures flexibility in allocation of resources – established between MMV and a Pharmaceutical or Biotechnology partner – from one project to another. In this way, resources are utilized as efficiently as possible.

Our partners provide drug discovery expertise, and many further contributions both in-kind and financial. Each miniportfolio agreement has allowed us access to new compound libraries for high content screening. And each library provides us with an immense treasure trove of new starting points for medicinal chemistry to feed the entire pipeline.

Heterocycles

Lead optimisation

Project Leader: Dr Stacie Canan, Celgene Corporation, CA, USA

MMV Project Director: Dr Paul Willis

Celgene have screened compounds from their collections against the malaria parasite and identified a number of series as suitable chemical starting points. A series is currently being optimised with the objective of making an early lead transition by the end of Q4 2014. Further screening is ongoing to identify additional lead series.

Heterocycles

Lead optimisation

Project Leader: Prof. Luiz Carlos Dias, Instituto de Química, UNICAMP, Brazil

Partners: Swiss Tropical and Public Health Institute, Switzerland; Monash University, Australia

MMV Project Director: Dr Paul Willis

The project is investigating a number of hit-to-lead series identified from high throughput screening. The goal is to identify a lead optimisation series with the potential to deliver an antimalarial drug with a long-duration of action.

Screening

Lead optimisation

Project leader: Dr Tomoyuki Shibata, Daiichi-Sankyo, Japan

MMV Project Director: Dr Jeremy Burrows

This project involves screening compounds from Daiichi-Sankyo’s library against the asexual blood stages of malaria with actives then being tested against gametocytes. This screening is being performed by Prof. Vicky Avery at Eskitis. In addition, the library is being screened against asexual liver stages with Prof. Elizabeth Winzeler at The University California, San Diego. The next milestone is the delivery of new hit series, by 3Q 2014. This collaboration is being supported by Global Health Innovative Technology fund.

Screening

Lead optimisation

Project Leader: Dr Mitsuyuki Shimada, Takeda, Japan

MMV Project Director: Dr Jeremy Burrows

This project involves screening compounds from Takeda’s library against the asexual blood stages of malaria with actives then being tested against gametocytes. This screening is being performed by Prof. Vicky Avery at Eskitis. In addition, the library is being screened against asexual liver stages with Prof. Elizabeth Winzeler at The University California, San Diego. These screening activities will be completed and if potent, novel, attractive compounds are identified, deliver new hit series later in 2014. This collaboration is being supported by the Global Health Innovative Technology fund.

Screening

Lead optimisation

Project Leader: Dr Nao-aki Watanabe, Eisai, Japan

MMV Project Director: Dr Jeremy Burrows

This project involves screening compounds from Eisai’s library against the asexual blood stages of malaria with actives then being tested against gametocytes. This screening is being performed by Prof. Vicky Avery at Eskitis. In addition, the library is being screened against asexual liver stages with Prof. Elizabeth Winzeler at The University California, San Diego. The next milestone is the delivery of new hit series. This collaboration is being supported by Global Health Innovative Technology fund.

Pathogen Box

Lead optimisation

MMV Project Director: Dr Thomas Spangenberg

Partners: As an open science project, anyone is welcome to participate 

The Pathogen Box will be a set of ~400 diverse, drug-like compounds with demonstrated activity against a range of neglected diseases. Upon request, it will be distributed free of charge to researchers, to further novel drug discovery research programmes and enhance collaborations. All that is asked in return, as with its sister project the Malaria Box, is that any data generated is shared in the public domain within 2 years of its generation.

The project is supported by the Bill & Melinda Gates Foundation and MMV will collaborate with partners to organize the selection, synthesis and procurement of the compounds. MMV will also organize the confirmatory testing and plating of these compounds for dispatch. The Pathogen Box is expected to be available for distribution in 4Q 2015.

The Pathogen Box is one of eight projects selected for further consideration by the WHO Consultative Expert Working Group on Research and Development: Financing and Coordination (CEWG) that seeks to fund truly innovative projects that can demonstrate “sustainable and scalable innovative financing and coordination mechanisms”.

16 Other Projects

Lead optimisation

MMV currently has 16 other projects underway to identify compounds that meet the MMV early lead criteria.