MSD partners with local research institution on infectious disease drug

Pharma News: A new antimalarial drug candidate, discovered through a longstanding collaboration between Walter and Eliza Hall Institute of Medical Research (WEHI) and pharmaceutical company Merck Sharp and Dohme (MSD) has entered Phase 1 clinical testing in healthy participants.

The initiation of this first-in-human trial is a crucial step in the development of a novel agent for the fight against malaria – a disease that kills more than 600,000 people each year. The therapeutic options are scarce and challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control.

Professor Alan Cowman, an international malaria expert who recently won the CSL Florey Medal for his outstanding research contributions to the field, said that the preclinical profile observed to date makes it a promising new antimalarial drug candidate.

“In pre-clinical studies we’ve shown this compound inhibits two enzymes that process and activate key proteins that enable the parasites to move in and out of red blood cells,” Cowman, deputy director at WEHI and a Laboratory Head in the Infectious Diseases and Immune Defence Division, said.

“The pre-clinical studies indicate that inhibiting these two enzymes — Plasmepsin IX (PMIX) and Plasmepsin X (PMX) — effectively disables the parasite from carrying out its key function of replicating and multiplying in the bloodstream. The successful initiation of these first-in-human trials is an important milestone towards developing urgently needed new treatments that could alleviate this major global health burden.”

As new malaria parasites increasingly become resistant to available drugs, the development of vaccines and novel antimalarial compounds to block transmission is vital in the fight against this killer disease.

MSD scientist and US team lead Dr David Olsen said “Efforts to develop drugs for malaria typically focus on disrupting a novel parasitic process or pathway to avoid pre-existing drug resistance and, ideally, are active at multiple stages of the lifecycle. By inhibiting two essential parasitic enzymes, this molecule met both criteria with the potential to provide a high barrier for the development of drug resistance.”

The compound is the result of an eight-year collaboration between WEHI and MSD, dedicated to discovering new widely applicable malaria drug candidates.

In 2022, the research collaboration published findings from preclinical experiments that revealed how a new class of antimalaria compounds worked to stop parasites from spreading in the blood. The team plans to present the results from this initial clinical trial at a future scientific meeting and further clinical trials are being planned.

The project was supported by the Wellcome Trust, the Victorian Government and the National Health and Medical Research Council (NHMRC).

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