DNDi and our partners are working to accelerate research to prepare for future viral pandemics. Utilizing our experience in non-profit drug development and partnerships with medical research institutions worldwide, our drug discovery teams are focused on identifying new broad-spectrum antivirals targeting several families of viruses recognized by WHO as presenting the greatest epidemic and pandemic potential in humans. Employing open science, AI, and cutting-edge research tools, our goal is to advance new drug candidates through Phase I safety trials to have them ready for testing against emerging viruses with pandemic potential.
Our progress in 2024 includes:
Discovery
Nucleoside Booster: All 23 nucleosides selected for primary screening (four with broad-spectrum antiviral activity and 19 with more restricted specific antiviral activity, based on primary screening data) have been resupplied to the six DZIF-affiliated screening centres for dose-response measurements against 10 viral diseases using 17 distinct viral assay systems. Parallel testing for cytotoxicity of these 23 compounds was also undertaken in seven cell lines. Analysis of all acquired data identified four promising candidates associated with broad-spectrum antiviral activity in the viral assays.
TMEM16 series: New salicylamide derivatives with improved physiochemical profiles have been designed and synthesized, confirming that it is feasible to significantly improve the drug property profiles of compounds in the series. Work is now focused on improving the antiviral potency of the compounds in the sub-series and confirming a favourable plasma exposure profile before assessing in vivo antiviral efficacy.
COVID Moonshot: The Moonshot backup compound, ASAP-0017445, has now progressed to a stage that allows for exploratory dose-range-finding or maximum-tolerated-dose studies with sufficient amounts of material synthesized to support these studies (>400 g). Extensive in vitro pre-clinical profiling indicates a very promising profile, in addition ASAP-0017445 show in vitro and in vivo efficacy against a panel of human and non-human coronaviruses. Pharmacokinetic characterization across multiple species and a promising preliminary human dose prediction further support progression of this compound.
AViDD ASAP: The project continued its focus on the discovery and development of novel antiviral drugs targeting three viral families: flaviviruses, coronaviruses, and enteroviruses. The leading programme targeting MERS/SARS-CoV-2 MPro inhibitors selected a shortlist of compounds that confirms MERS-CoV activity in pre-clinical infection models. These compounds are now being progressed towards pre-clinical toxicology studies. A second programme focused on the discovery of dengue and Zika virus NS2B-NS3 protease inhibitors has now entered the lead-optimization phase with the aim of developing a compound with confirmed in vivo efficacy.
Development
ANTICOV: A total of 1,942 patients were randomized in 12 countries prior to the study’s conclusion. Database lock was completed in November 2023, and data were transferred to the Infectious Diseases Data Observatory (IDDO) platform to ensure worldwide accessibility to other researchers. Final results were available in December 2023. The clinical study report was completed in March 2024.
ANTICOV was completed in 2024, with five treatments tested. Early futility was demonstrated for one arm, but due to the low probability of reaching any statistical significance after the Omicron wave, it was decided to stop the study.
Photo credit: Yaw Afrim Gyebi-DNDi
