WORMZERO Pipeline
WORMZERO is a focused helminth drug discovery pipeline built from the WORMZERO Challenge proposal: parasite biology, AI compound triage, and functional screening combined to advance wormspecific targets and candidates toward translational readiness.
The problem today
Helminth drug discovery still relies on a handful of old pharmacological pillars, even though demand is large and resistance risk is rising. WORMZERO is designed to address the critical gaps in each major human worm group by advancing new target families, candidate concepts and downstream screening partnerships.
| Worm group | Current backbone | Critical gap |
|---|---|---|
| Soil-transmitted helminths | albendazole, mebendazole; ivermectin/albendazole emerging | weak Trichuris efficacy, Strongyloides gap, reinfection, resistance risk |
| Schistosomiasis | praziquantel / arpraziquantel | juvenile worms, reinfection, single-class dependence |
| Filarial worms | ivermectin, DEC, albendazole, moxidectin; doxycycline anti-Wolbachia | adult worms persist for years; short-course macrofilaricides are lacking |
| Cestodes | praziquantel, niclosamide, albendazole/oxfendazole concepts | larval tissue stages, cyst penetration, One Health reservoirs |
WORMZERO candidate and target focus
The WORMZERO proposal emphasises parasite-selective, conserved vulnerabilities that are testable with modern AI and helminth assays. Candidate target families include:
- latrophilin / SLO-1 / BK-channel signalling
- GluCl channels
- nicotinic acetylcholine receptors
- β-tubulin
- schistosome TRPM_PZQ biology
- Wolbachia-essential pathways
- kinases and proteostasis
- tegument and cuticle maintenance
- flatworm germinal and stem-cell systems
How WORMZERO works
WORMZERO is framed as a $10M Challenge programme to catalyse 10–20 academia × industry initiatives across the helminth drug-discovery pipeline: target discovery, AI compound triage, functional screening, lead optimisation, resistance testing and early clinical acceleration.
The programme is built on the hypothesis that worms contain conserved pathway bottlenecks that are essential for parasitism and costly to evolve around. It combines comparative genomics, parasite-selective target prioritisation, AI-enabled compound nomination, and high-content functional assays.
Pipeline stages
- Target discovery: comparative genomics, orthologue analysis and druggability filtering for conserved worm vulnerabilities.
- AI triage: computational compound nomination, generative chemistry and in silico screening focused on parasite-selectivity.
- Functional screening: activity profiling across motility, viability, development, fecundity, stage specificity and resistance risk.
- Candidate progression: chemistry, pharmacology and partner-led translational readiness for the most credible early-stage leads.
Why this matters
The current helminth pipeline is fragmented and underfunded, and existing drug classes are often stage-limited or vulnerable to resistance. WORMZERO aims to make helminth drug discovery data-driven, coordinated and ready for real-world translation.
How to contribute
Visit the Collaborate page to describe your expertise and participate in the WORMZERO pipeline as an assay partner, discovery collaborator, or translational contributor.