Monoclonal Antibody in Development for Malaria Will Move Ahead This Year

Scott Miller

Malaria continues to impact low-to-middle income countries in sub-Saharan Africa, India, and parts of south Asia. According to the World Health Organization (WHO), malaria kills over 600,000 people annually with the most recent figure estimating 619,000 people succumbed to the disease in 2021.

April 25 marked World Malaria Day, which serves as a reminder for people here in the United States and other places where malaria is not endemic of its health care footprint on populations. Malaria used to be endemic in the US before a concerted effort was made through spraying and it was declared eliminated in the country in 1951.

In recent weeks, the University of Oxford announced the malaria vaccine, R21/Matrix-M, was approved for use in Ghana (one of the endemic countries.)

The vaccine was a collaborative effort between Oxford, the Kenya Medical Research Institute, the London School of Hygiene & Tropical Medicine, Novavax, and the Serum Institute of India.

Another organization hard at work on this vector-borne disease is The Bill & Melinda Gates Medical Research Institute. Gates MRI has collaborated with Atreca on development of MAM01 (Mosquirix), a novel monoclonal antibody (mAb) that could provide prolonged protection against malaria infection is something the organization is working on. Specifically, their program aims to develop this prophylactic monoclonal antibody to prevent malaria caused by P falciparum for 3-6 months (during the rainy season) post-administration in children 3 years of age to less than 60 months of age in seasonal malaria chemoprevention (SMC) eligible areas, endemic countries, and any countries with active malaria outbreaks.

Scott Miller, MD, clinical development leader, Malaria Program, Gates Medical Research Institute recently spoke to Contagion and he offered some insights about the antibody and the foundation’s plans in this area.

Contagion: Although the United States has not seen the issue of malaria for a number of years, with climate change, malaria could come possibly come back to this country in greater numbers. What should clinicians and the general public know about this?
Miller: Malaria was eliminated in the United States in the 1950s. There are over 2,000 cases of malaria imported into the Unites States each year by travelers returning from malaria endemic areas. Anopheles mosquitoes are still found in many parts of the US, and local outbreaks have occurred from these returning travelers, but are never sustained due to improvement in housing. Therefore, malaria re-reintroduction would be very unlikely despite climate change, unlike the enhanced risk from dengue or other viruses.

Contagion: In terms of the Gates malaria program overall, can you provide an update of the latest initiatives and news on it?
Miller: The malaria program at the Gates MRI is new, starting in the past year. Our first product development effort is on the monoclonal antibody, but we also plan to work on vaccines for persons of all ages to help in malaria elimination.

Contagion: In thinking about The Gates MRI’s collaboration with Atreca on development of MAM01 that could provide protection against malaria infection. Can you provide an overview of the therapy and its mechanism of action?
Miller: MAM01 is a long-acting injection drug for the prevention of falciparum malaria. It is a monoclonal antibody targeting a conserved region of the dominant protein on the surface of the sporozoite, the invasive stage of the parasite inoculated by the mosquito in its saliva.

The antibody has been modified to optimize manufacturability and to extend its half-life. Its mechanism of action is to bind the sporozoite in the skin or the bloodstream to prevent mobility and allow destruction by the human immune system. Further details on its selection and optimization can be found in a new paper on a pre-print site.

Contagion: How far along is this therapy in terms of clinical trials?
Miller: The phase 1 trial will start in the second half of this year in the US and next year in sub-Saharan Africa.