Introduction and Background of the Project

Introduction

Malaria continues to be a major public health problem with more than 282 million cases and 610,000 deaths estimated in 2024 worldwide*1. Since Malaria acutely exacerbate and threat the lives, prevention holds the crucial measure to save lives in limited healthcare access settings. The WHO recommended chemoprevention programs for the most vulnerable people are widely accepted and expanding the eligible populations. For example, the seasonal malaria chemoprevention is providing prevention to 54 million children in 2024. Although the current first line oral drug regimen is generally well tolerated and effective, they suffer from parasite resistance and incomplete adherence issues. In addition, monthly distribution of oral drugs to every household requires substantial resources and cost in resource limited settings. The highly effective small molecule long-acting injectables (LAI) which can cover the whole transmission season would provide a simpler and cost effective option for not only in seasonal, but also in perennial transmission settings.

Project Objective

A promising preclinical candidate that target malarial electron transport chain was identified in the collaboration among Nagasaki University, Japan Institute for Health Security, Shionogi and Medicines for Malaria Venture (MMV) under the GHIT Fund financial support. The candidate showed promising broad malaria lifecycle intervening activities, useful for prophylaxis and transmission block as well as treatment. This project aims to conduct the CMC (Chemistry, Manufacturing, and Controls) research and development, manufacturing of API and investigational drug product, preclinical development of the candidate, and complete the Clinical Trial Application (CTA) for Phase 1.

Project Design

This project aims to complete the CTA for Phase 1 in 2 years. The activities will include the Active Pharmaceutical Ingredient (API) and the formulation research and development, manufacturing of API and investigational drug product, and non-clinical studies to enable CTA.

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

Malaria is a major public health issue, particularly affecting children under the age of five, and poses significant healthcare and economic burden in afflicted countries. Despite the WHO and the world’s effort for malaria elimination and eradication*2, the number of cases and deaths remains persistently high. Therefore, there is a critical need for more effective and novel intervention tools. We aim to develop a LAI that could cover the whole transmission season by single injection with broad malaria lifecycle intervening activities, useful for chemoprevention*3. A highly effective and convenient LAI has the potential to overcome current limitations associated with oral chemoprevention drugs. It may also be useful in perennial transmission settings where chemoprevention programs are currently lacking, or in the remote areas where monthly drug delivery is logistically challenging. We aim to free the most vulnerable people from the threats and burdens imposed by malaria, contributing significantly to the global agenda of malaria elimination and eradication.

What sort of innovation are you bringing in your project?

Our innovation focuses on the development of a LAI for malaria chemoprevention. When a LAI is injected intramuscularly or subcutaneously, the active ingredient is slowly absorbed into the body, ensuring sustained efficacy over an extended duration. This stands in contrast to the current approach, where chemoprevention relies on the monthly distribution of oral drugs to households, contingent on individual’s willingness to complete the regimen every month. Therefore, the proposed LAI introduces a groundbreaking shift by offering a seasonal, single dose solution. Our innovative LAI has the potential to transform current chemoprevention programs.

Role and Responsibility of Each Partner

Shionogi takes the lead of API and investigational drug product research and development,  manufacturing, non-clinical studies to enable CTA, and the design of clinical trials. Nagasaki University would conduct pharmacological non-clinical studies and join forces to design the clinical trials. MMV supports the project by giving advice based on their expertise of antimalarial non-clinical studies and clinical trial design, and provides essential assays crucial for further characterization.

Others (including references if necessary)

1, World Malaria Report 2025, WHO

https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2025

2, Global technical strategy for malaria 2016-2030, 2021 update, WHO

https://www.who.int/publications/i/item/9789240031357

3, Gaaloul M. E. et al., Chemoprevention of malaria with long-acting oral and injectable drugs: an updated target product profile, Malaria Journal, 2024, 23, 315.

https://link.springer.com/article/10.1186/s12936-024-05128-1