Malaria, a parasitic infection transmitted by mosquitoes, kills hundreds of thousands of people every year. While there are treatments available, the parasites that cause malaria are becoming drug-resistant—meaning that new options are severely needed, particularly in Asia and Africa where the disease is most prevalent.

Efforts to address this need include the novel malaria drug candidate CMQ069, which has been selected as Project of the Year 2023 by Medicines for Malaria Venture, a Swiss-based not-for-profit working to develop new medicines to treat, prevent and eliminate malaria. CMQ069 is a small-molecule compound designed with a long duration of action that has the potential to cure patients with a single, oral dose and prevent malaria infections for up to a month. These properties are expected to enhance adherence to taking the drug, as currently approved therapies require multiple-day administration, which can be difficult to follow and lead to drug resistance. CMQ069 was thoughtfully designed by the Calibr-Skaggs Institute for Innovative Medicines, the drug discovery arm of Scripps Research, in collaboration with MMV and with funding from the Bill & Melinda Gates Foundation.

The independent Expert Scientific Advisory Committee (ESAC) at MMV annually selects a promising drug compound from MMV’s supported projects as their “Project of the Year.” The committee chose CMQ069 based on its ability to address malarial drug resistance, as well as act as a long-duration preventive treatment. According to MMV, the ESAC recognized the Calibr-Skaggs team’s rigorous focus in the optimization process, which is critical to achieving such challenging target candidate profiles.

“The Calibr-Skaggs team has a long-standing collaboration with MMV and the Bill & Melinda Gates Foundation, working on the identification of both oral and injectable antimalarial drug candidates,” says Anil Gupta, PhD, co-project lead and director of chemistry at Calibr-Skaggs. “It took three years of perseverance to achieve these breakthrough results.”

According to UNICEF, a child under five dies of malaria every minute. Approximately 608,000 people died from malaria in 2022 alone, meaning it remains one of the most severe infections around the world. And while artemisinin-based therapies have saved countless lives, partial drug resistance is now being detected, and treatments with novel mechanisms are greatly needed.   

In preclinical studies, CMQ069 has been shown to have high efficacy and a long duration of action. Because it has a novel mechanism of action, an oral route of administration, and the potential to be a low-dose treatment, it could provide an alternative to current artemisinin-based options.  

CMQ069 also shows promise in acting as a chemoprevention—providing proactive protection against those who are geographically at higher risk of infection. By following a single monthly oral dose, the compound could improve wide-scale malaria prevention strategies and serve as a more seamless, cost-effective option for people around the world.

CMQ069 is currently being studied in investigational new drug (IND)-enabling safety studies at Calibr-Skaggs, with funding from the John C. Martin Foundation. With continued success, CMQ069 could enter a first-in-human phase 1 clinical trial in early 2025.

In addition to Gupta, additional Calibr-Skaggs project team members include Arnab Chatterjee, Case McNamara, Jenya Antonova-Koch and Peter Schultz, as well as MMV members James Duffy, Anne Cooper and Peter Webborn.