A·WOL II: Discovery & Development of Macrofilaricidal Drugs & Regimens

The overall goal of the project was to optimize drugs and regimens of registered and re-purposed anti-Wolbachial macrofilaricidal drugs selected from A∙WOL I screening outputs and test these in combination with standard anti-filarial drugs (SAFD). 

Optimal drugs and regimens were determined using PK/PD analysis and modeling and in vivo evaluation in the adult Brugia malayi mouse model. The goal was to determine whether these outputs can shorten treatment time to a 7 day, or 2 x 7 day, treatment duration aligned with the BMGF TPP of 7 days or less.

The programme consists of two major aims: A∙WOL Macrofilaricidal Drug Development and Macrofilaricide Drug Discovery

A∙WOL Macrofilaricidal Drug Development aims to optimize regimes of registered and re-purposed anti-Wolbachial macrofilaricidal drugs in combination with anti-filarial drugs.

Macrofilaricide Drug Discovery aims to progress the best outputs from the A∙WOL I screening campaigns through a rigorous lead optimization and candidate selection process in order to deliver at least one novel pre-clinical candidate and a chemically distinct back-up within 36 months. The pre-clinical candidates will have the potential for full development as a monotherapy in the first instance. We will undertake the lead optimization of lead series emerging from three independent hit finding campaigns. These programmes will be developed in competition with each other and against our Target Candidate Profile (TCP) that is aligned with established Target Product Profiles for a new anti-Wolbachia based macrofilaricide. Advice about progression and prioritization will be generated through the experts on our ESAC and our industrial partners. To compliment these activities we will also undertake additional targeted screening activities with the specific aim of identifying hits with significant improvements in anti-Wolbachia activity and times to cure compared with the other leads in the portfolio. These would need to be seen as game-changing molecules in terms of anti-Wolbachia based macrofilaricide drug development.

Completed, outputs now to be brought forward into A∙WOL III