Annovis’ Lead Compound Enhances Cognition Synergistically with GLP-1 Agonist

Annovis Bio Inc. recently announced new preclinical data demonstrating the synergistic effect of its lead compound, buntanetap, when combined with the glucagon-like peptide 1 (GLP-1) agonist dulaglutide (Trulicity) in a mouse model of Alzheimer’s disease.

GLP-1 agonists, commonly used to treat diabetes, weight loss, and heart conditions, are now showing promising potential in the treatment of Alzheimer’s disease. Recent data presented at the Alzheimer’s Association International Conference (AAIC) 2024 revealed that another GLP-1 agonist, liraglutide (Victoza), was able to decrease cognitive decline in Alzheimer’s patients by 18% and reduce brain shrinkage in regions responsible for cognitive functions.

In 2018, Annovis Bio published data showing that buntanetap fully restored memory, learning, and synaptic potentiation in an Alzheimer’s mouse model (Teich et al. 2018). Building on this research, Annovis recently investigated whether combining buntanetap with the GLP-1 agonist dulaglutide would produce a synergistic effect in the same animal model. The results were compelling: while buntanetap alone restored cognitive function to 100% and dulaglutide alone to 80%, the combination of these two compounds not only restored cognitive function but also enhanced it beyond levels seen in healthy controls.

The ability of GLP-1 agonists to penetrate the brain is linked to their molecular structure. Single-chain peptides (i.e. dulaglutide, albiglutide, exenatide) have better blood-brain barrier (BBB) permeability than bifurcated molecules containing side chains. Due to its excellent BBB permeability, dulaglutide was chosen from other GLP-1 agonists for combination with buntanetap.

“We are excited to see that buntanetap significantly amplifies the effects of dulaglutide on memory and learning, with a 6- to 10-fold increase in efficacy,” said Maria Maccecchini, PhD, Founder, President, and CEO of Annovis Bio. “This synergy is particularly important for enhancing treatment outcomes while minimizing potential side effects. As the field of Alzheimer’s research shifts towards combination therapies, we believe our approach holds great promise for offering more effective treatment options for patients.”

Buntanetap (formerly known as Posiphen) targets neurodegeneration by inhibiting the formation of multiple neurotoxic proteins, including amyloid beta, tau, alpha-synuclein, and TDP43. This improves synaptic transmission, axonal transport, and reduces neuroinflammation. Dysregulation of these pathways has been shown to cause nerve cell degeneration and ultimately nerve cell death. By targeting these pathways, buntanetap has the potential to reverse neurodegeneration in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases, thereby aiming to restore brain function and improve the quality of life for patients.

Headquartered in Malvern, PA, Annovis Bio Inc. is dedicated to addressing neurodegeneration in diseases such as AD and PD. The company’s innovative approach targets multiple neurotoxic proteins, aiming to restore brain function and improve the quality of life for patients. For more information, visit www.annovisbio.com.