M5717 (formerly DDD498)

Dr Jutta Reinhard-Rupp, Head of Merck Global Health Institute, Merck Group

M5717 was identified through a collaboration between MMV and the Drug Discovery Unit, University of Dundee, Scotland. It is a compound with a novel mechanism of action, targeting the protein-making machinery of the malaria parasite. The compound has demonstrated activity against all stages of the malaria parasite’s lifecycle and thus has the potential both to treat and to protect vulnerable populations.

M5717 is being developed in partnership with Merck KGaA. Merck has included volunteer infection studies in their M5717 development programme, representing the first time VIS have been conducted by a pharmaceutical company as part of phase I. The goal of the studies is to understand the drug’s efficacy against the blood stage of the malaria parasite’s lifecycle earlier than previously possible. M5717 was also tested in combination with other compounds from the MMV portfolio in a mouse model of human malaria, to enable the selection of combination partners for further development.

Dr Jutta Reinhard-Rupp, Head of Merck Global Health Institute, Merck Group, talks about the vision of the Merck Global Health Institute, its partnership with MMV, and how volunteer infection studies (VIS) are contributing to the clinical evaluation of M5717.

1. What is exciting about M5717 as a potential antimalarial?

Preclinical studies have shown M5717 is active against all stages of the malaria lifecycle and is long acting. This unique profile suggests an important role in the future treatment of malaria. We are very excited about the initial data, and hope that the compound will live up to our expectations during clinical development.

2. What led to Merck partnering with MMV?

It started with Merck’s interest in neglected tropical diseases – especially schistosomiasis – and some early research in the field of malaria. These elements came together with the creation of the Merck Global Health Institute, which is dedicated to developing health solutions for the most vulnerable populations in developing countries.

Malaria is still one of the top killers of children, so we urgently need new antimalarials. Partnering with MMV allows us to benefit from their malaria expertise and gives MMV access to our R&D expertise, helping to ensure our joint programmes move forward.

3. How are the phase I trials progressing, and what is the role of the VIS platform?

We started the first-in-human (FiH) phase I study in September 2017; this included a VIS in Brisbane, Australia. FiH phase I trials are ‘business as usual’, but the VIS platform is a new area for us. We hope it will provide us with an early understanding of drug efficacy, which will guide the design of our phase II trials. It’s about finding ways to reduce timelines, manage resources and minimize the number of patients needed in the trials. Initial data are promising, and step by step we will see if all the expectations we have for this compound are realized.