Annovis’ Lead Compound Boosts Cognition with GLP-1 Agonist

Annovis Bio Inc., based in Malvern, Pennsylvania, announced promising new preclinical results for its lead compound, buntanetap, when used in combination with the GLP-1 agonist dulaglutide (Trulicity®) in an Alzheimer's disease mouse model. The company, recognized for its pioneering treatments for neurodegenerative diseases like Alzheimer's (AD) and Parkinson's (PD), has revealed that this combination therapy shows significant promise in enhancing cognitive function.

GLP-1 agonists, primarily used for diabetes, weight reduction, and cardiovascular conditions, are now being explored for their potential benefits in Alzheimer's treatment. Research recently presented at the Alzheimer’s Association International Conference 2024 highlighted the efficacy of another GLP-1 agonist, liraglutide (Victoza), in slowing cognitive decline and reducing brain atrophy in Alzheimer's patients.

In 2018, Annovis Bio published findings indicating that buntanetap could fully restore memory, learning, and synaptic potentiation in an Alzheimer's mouse model. Building on this foundation, the company has now explored the impact of combining buntanetap with dulaglutide. The results were noteworthy: while buntanetap alone restored cognitive functions to 100% and dulaglutide alone to 80%, their combination not only fully restored but also enhanced cognitive function beyond levels observed in healthy controls.

The selection of dulaglutide over other GLP-1 agonists was based on its molecular structure, which allows for better penetration of the blood-brain barrier. Single-chain peptides like dulaglutide have been shown to have superior blood-brain barrier permeability compared to bifurcated molecules with side chains, making dulaglutide the preferred choice for this study.

Maria Maccecchini, Ph.D., Founder, President, and CEO of Annovis Bio, expressed enthusiasm over the findings, stating that buntanetap significantly amplifies the cognitive benefits of dulaglutide, achieving a 6- to 10-fold increase in efficacy. She emphasized the importance of this synergy in improving treatment outcomes while reducing potential side effects, aligning with the industry's shift towards combination therapies for Alzheimer's.

Buntanetap, previously known as Posiphen, targets neurodegeneration by inhibiting the formation of multiple neurotoxic proteins such as amyloid beta, tau, alpha-synuclein, and TDP43. This inhibition improves synaptic transmission, enhances axonal transport, and decreases neuroinflammation, all of which are crucial for combating nerve cell degeneration and death. By addressing these pathways, buntanetap holds the potential to reverse neurodegeneration in diseases like Alzheimer's and Parkinson's, aiming to restore brain function and enhance patients' quality of life.

Annovis Bio Inc. remains committed to addressing neurodegenerative diseases through innovative approaches that target multiple neurotoxic proteins. The company's endeavors are focused on restoring brain function and improving life quality for those affected by conditions like Alzheimer's and Parkinson's.

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