Evaluate the Safety, Tolerability, and Immunogenicity of Adjuvanted Preventive Dual Aβ/tau Vaccine, Duvax in Healthy Volunteers

Project Summary Alzheimer's disease (AD) represents the most prevalent form of dementia, characterized by memory impairment and changes in multiple cognitive functions. This complex condition arises from a blend of genetic and environmental influences, culminating in hallmark pathologies like β-amyloid (Aβ) oligomers/fibrils/plaques and tau aggregates/tangles, followed by inflammation and severe neurodegeneration. The modern "amyloid cascade" hypothesis emphasizes the pivotal role of Aβ oligomers in initiating tau pathology and subsequent inflammatory responses, oxidative stress, and synaptic and neuronal loss, while the accumulation of pathological tau is directly correlated with the disease progression and severity. Therefore, the development of potential therapies for AD has been mainly focused on reducing pathological Aβ or tau and, more recently, on inflammation associated with accumulating these pathological molecules in the brain. Increasing evidence underscores the synergistic pathogenic interaction between Aβ and tau, sparking interest in therapies concurrently addressing both. Scientists from the Institute for Molecular Medicine (IMM) advocate for an immunogenic dual vaccine targeting both Aβ and tau pathologies, deeming it optimal for inhibiting Aβ aggregation, reducing tau accumulation, and potentially delaying clinical AD onset. This vision led to the creation of Duvax, an adjuvanted (AdaxCpG), MultiTEP vaccine platform-based dual vaccine, demonstrating promising immunogenicity and efficacy in rigorous AD mouse models. They finalized all FDA-required IND-enabling studies, including: (i) manufacturing of cGMP recombinant protein (drug product) with CMC information; (ii) safety/toxicology studies of Duvax in disease model of Tg mice. Nuravax, Inc., having licensed Duvax, collaborates with IMM and proposes in phase 1 of this program (R43) to define the safe and immunogenic optimal dose range of Duvax in non-human primates, concurrently preparing and submitting the IND30496 application to the FDA for Phase 1 safety and immunogenicity trials in healthy human subjects. Transitioning into phase 2 (R44), Nuravax plans a randomized, double-blind, placebo-controlled study to evaluate Duvax's safety/tolerability and immunogenicity in male and female healthy volunteers aged 40-65 years. Completion of this comprehensive study will provide essential data supporting future Phase 2 trials tailored for age-matched preclinical AD populations, advancing our comprehension and potential treatment avenues for this debilitating condition.