AWZ1066S / Eisai, Liverpool School of Tropical Medicine, University of Liverpool - LARVOL DELTA

The long and winding road towards new treatments against lymphatic filariasis and onchocerciasis. (PubMed, Trends Parasitol) - "Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing."

Journal • Review • Infectious Disease

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Trial of AWZ1066S, an Anti-Wolbachia Candidate Macrofilaricide. (PubMed, Clin Pharmacol Drug Dev) - "Pharmacokinetic analysis indicated that AWZ1066S is rapidly absorbed with predictable pharmacokinetics. In conclusion, safety concerns prevented this study from reaching the human exposures needed for AWZ1066S to be clinically effective against lymphatic filariasis and onchocerciasis."

Clinical • Journal • P1 data • Gastrointestinal Disorder • Infectious Disease

Combinations of the azaquinazoline anti-Wolbachia agent, AWZ1066S, with benzimidazole anthelmintics synergise to mediate sub-seven-day sterilising and curative efficacies in experimental models of filariasis. (PubMed, Front Microbiol) - "We determined that short-course AWZ1066S-albendazole co-treatment significantly augmented the depletion of Wolbachia populations within both germline and hypodermal tissues of B. malayi female worms and in hypodermal tissues in male worms, indicating that anti-Wolbachia synergy is not limited to targeting female embryonic tissues. Our data provides pre-clinical proof-of-concept that sub-seven-day combinations of rapid-acting novel anti-Wolbachia agents with benzimidazole anthelmintics are a promising curative and transmission-blocking drug treatment strategy for filarial diseases of medical and veterinary importance."

Journal • Infectious Disease

AWOL: Development of AWZ1066S, a Small Molecule Anti-Wolbachia Candidate Macrofilaricide Drug (clinicaltrials.gov) - P1 | N=30 | Terminated | Sponsor: Liverpool School of Tropical Medicine | N=80 ➔ 30 | Trial completion date: Jul 2022 ➔ May 2023 | Not yet recruiting ➔ Terminated | Trial primary completion date: Jul 2022 ➔ May 2023; Safety issues

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Infectious Disease

Dirofilariasis mouse models for heartworm preclinical research. (PubMed, Front Microbiol) - "We established an ex vivo L4 paralytic screening system whereby assays with moxidectin or levamisole highlighted discrepancies in relative drug sensitivities in comparison with in vitro-reared L4 D. immitis. We demonstrated effective depletion of Wolbachia by 70%-90% in D. immitis L4 following 2- to 7-day oral in vivo exposures of NSG- or NXG-infected mice with doxycycline or the rapid-acting investigational drug, AWZ1066S. We validated NSG and NXG D. immitis mouse models as a filaricide screen by in vivo treatments with single injections of moxidectin, which mediated a 60%-88% reduction in L4 larvae at 14-28 days. Future adoption of these mouse models will benefit end-user laboratories conducting research and development of novel heartworm preventatives via increased access, rapid turnaround, and reduced costs and may simultaneously decrease the need for experimental cat or dog use."

Journal • Preclinical • Genetic Disorders • Immunology • Infectious Disease • Obesity • Primary Immunodeficiency • IL2