NTD Drug Discovery Booster Hit-to-lead
Speed up the process and cut the cost of finding new treatments for Chagas disease and leishmaniasis by bringing together pharmaceutical companies in a multilateral, simultaneous, and non-competitive search process
last phase of drug development
updated 16 Feb 2023
The NTD Drug Discovery Booster was launched in 2015 to circumvent early-stage commercial barriers between pharmaceutical participants, allowing DNDi to search millions of unique compounds simultaneously, using computational approaches to refine the search iteratively, in the hunt for new treatment leads.
Dr Bernard Pécoul, Founder, DNDiThis experiment could significantly reduce the time and money it takes to find new, promising treatment leads, and echoes the great potential of innovative research and development collaborations.
The innovation of the NTD Drug Discovery Booster not only lies in the multilateral approach, but also in the iterative nature of the search, meaning companies will continually examine their libraries for better matches as the search is refined. This will significantly condense down the time it will take to find new, promising treatment leads.
The NTD Drug Discovery Booster consortium has engaged eight pharmaceutical companies to date: AbbVie, Astellas, AstraZeneca, Celgene (now part of Bristol-Myers Squibb), Eisai, Merck, Shionogi, and Takeda Pharmaceutical Company Limited. The Global Health Innovative Technology Fund (GHIT Fund), which launched in 2013 to assist international global health research and development partnerships, supported the involvement of the four Japanese companies through grants provided to DNDi, including an initial grant of EUR 640,000 (79.5 million Japanese Yen), a second grant of EUR 470,000 (55 million Japanese Yen), and a third grant of EUR 1.2 million (158 million Japanese Yen).
David Shum, Group Leader, Assay Development & Screening, Institut Pasteur Korea, South KoreaIPK joined DNDi’s new initiative, the NTD Drug Discovery Booster programme, that cuts the cost of early-stage drug discovery, accelerates and expands discovery of new drugs for NTDs. In 2016, we identified four hit series that are currently advancing to further development. It is our hope that we can soon identify a breakthrough compound for patients.
Since its creation in 2015, the NTD Drug Discovery Booster has launched 45 iterations around 22 seed compounds, with 13 hit series released, of which six have progressed to in vivo proof-of-concept studies for Chagas disease, leishmaniasis or both. Two compounds from one hit series have demonstrated efficacy in a leishmaniasis infection model: one was transitioned into lead optimization and is progressing to the pre-clinical stage with Takeda.
NTD Drug Discovery Booster screening activities were placed on hold in early 2019 to focus efforts on transitioning existing hit series into lead optimization projects.
Project updates
2022
Two leading examples from the most promising series arising from the project, based on seed S07, underwent intensive profiling to determine if either could be nominated as a pre-clinical candidate in 2023. Drug discovery elements of the project remained on hold but may be reactivated if needed in the coming years.
2020
Screening activities remained on temporary hold in 2020. However, the process of hit-to-lead optimization continued, with multiple series being progressed based on outputs of the screening programme. A variety of hit-to-lead mechanisms and exploration strategies are being used to progress towards in vivo proof-of concept studies in pre-clinical efficacy models of leishmaniasis. Two compounds from one hit series have demonstrated efficacy in a leishmaniasis infection model; one has been transitioned into lead optimization and is now being delivered as a pre-clinical candidate with Takeda Pharmaceutical Company Limited, funded by the GHIT fund.
2019
Screening activities were placed on temporary hold in early 2019 to focus efforts on transitioning existing hit series into lead optimization projects. Two hit series are currently under further investigation with Takeda Pharmaceutical Company Limited, and work is underway to transition additional series for potential lead optimization in 2020.
2018
In 2018, the Japanese pharmaceutical company Astellas Pharma Inc. joined the NTD Drug Discovery Booster, becoming the eighth company in the consortium.
Screening continued at the rate of one new iteration per month.
To date, the Booster project has launched 45 iterations around 22 seed compounds, with the result that 13 hit series have been released, of which six have progressed to in vivo proof-of-concept studies for Chagas and/or leishmaniasis.
2017
In 2017, two new companies – AbbVie and Merck – joined the Drug Discovery Booster, which included already Takeda, Eisai, Shionogi, AstraZeneca, and Celgene, bringing the total to seven participants.
To date, 32 iterations of the booster have been launched around 16 distinct seed compounds. Ten hit series have been identified, four of which will enter into proof-of-concept in vivo efficacy studies by Q1 2018.
News & resources
- 6 January 2023 - Collaborative virtual screening identifies a 2-Aryl-4-aminoquinazoline series with efficacy in an in vivo model of Trypanosoma cruzi infection, Journal of Medicinal Chemistry
- 1 July 2022 - NTD Drug Discovery Booster, Yakugaku Zasshi
- 19 May 2021 - Neglected disease program reimagines drug discovery with help from Atomwise’s AIMS Award, Atomwise
- 21 January 2021 - Collaborative virtual screening to elaborate an imidazo[1,2-a]pyridine hit series for visceral leishmaniasis, RSC Medicinal Chemistry
- 27 July 2020 - Five years of the Neglected Tropical Diseases (NTD) Drug Discovery Booster
- 29 March 2018 - DNDi welcomes Astellas to the NTD Drug Discovery Booster
- 1 January 2018 - NTD Drug Discovery Booster factsheet
- 18 April 2017 - Merck joins DNDi’s ‘Drug Discovery Booster’ to accelerate discovery of new treatments for neglected diseases
- 15 June 2016 - Celgene joins DNDi’s ‘Drug Discovery Booster’ to accelerate discovery of new treatments for neglected diseases
- 31 July 2015 - Finding a Cure for Kala Azar, Al Jazeera
- 30 July 2015 - Neglected Attention, BioCentury
- 1 June 2015 - Japanese Companies Attack Neglected Diseases, New York Times
- 28 May 2015 - The NTD Drug Discovery Booster
- 28 May 2015 - DNDi and four pharmaceutical companies announce ‘Drug Discovery Booster’ experiment to accelerate and expand discovery of new drugs for two highly neglected diseases – leishmaniasis and Chagas disease
Seed status
1st Seed: Hit series identified, in vivo efficacy observed in Chagas disease model, publication in progress
2nd Seed: Hit series released, optimization ongoing, publication in progress
3rd Seed: Hit series released, optimization ongoing with Open Synthesis Network
4th Seed: Stopped
5th Seed: Hit series released, in vivo efficacy observed in leishmaniasis model, publication in progress
6th Seed: Hit series released, publication in progress
7th Seed: Preclinical candidate to be nominated end of 2022.
8th Seed: 2 Hit series released
9th Seed: Stopped
10th Seed: Stopped
11th Seed: Stopped after 2 iterations
12th Seed: Stopped after 3 iterations
13th Seed: 2 Hit series identified, publication in progress
14th Seed: Hit series released, optimization ongoing
15th Seed: Stopped after 2 iterations
16th Seed: Hit series released, optimization ongoing
17th Seed: Stopped after 2 iterations
18th Seed: Stopped
19th Seed: Stopped after 2 iterations
20th Seed: Stopped after 2 iterations
21st Seed: Hit series identified
22nd Seed: Hit series released
Last updated: September 2022
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