BERWYN, PA — Annovis Bio Inc. (NYSE American: ANVS), a clinical-stage drug platform company addressing Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases, published data from its two double-blind, placebo-controlled animal studies in Alzheimer’s disease (AD) and Parkinson’s disease (PD) demonstrating in both diseases preclinical efficacy of ANVS401, the company’s lead compound.
“No drug to date has shown efficacy in two totally different animal models of neurodegeneration,” commented Maria Maccecchini, Ph.D., CEO of Annovis Bio. “In our AD animal studies, ANVS401 was shown to lower amyloid precursor protein (APP) and all its fragments, and animals fully recovered memory, learning, fear conditioning, and brain function. In our PD animal studies, ANVS401 lowered levels of α-synuclein and normalized gut motility in two transgenic animal models of PD. Together, these data are very exciting and provide strong support for moving forward in our development of ANVS401 for both AD and PD.”
The Alzheimer’s study, conducted by Professor Ottavio Arancio at Columbia University and published in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, is the first study demonstrating the therapeutic efficacy in animals of inhibiting the translation of APP and its fragments in an AD model. Translational inhibition of APP by ANVS401 has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of AD.
The study used a mouse model of AD to examine ANVS401’s efficacy, pharmacodynamics, and pharmacokinetics. In the study, ANVS401 treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual activity, motor skills, or motivation and without affecting wild-type mice. ANVS401 had a prolonged effect in reducing APP and all related peptides for at least nine hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N8-NorPosiphen.
The Parkinson’s study, conducted by Professor Robert Nussbaum at University of California San Francisco and published in the American Journal of Neurodegenerative Disease, is the first study showing the preclinical efficacy of ANVS401 in improving the colonic motility in mouse models of gastrointestinal dysfunction in early PD. This result demonstrates the ability of ANVS401 to reach the nervous system, and its mechanism of action, the translational inhibition of α-synuclein expression, supporting further development of ANVS401 as a drug for the treatment of PD.
The study used two α-synuclein transgenic mouse models to investigate the efficacy of ANVS401 in reversing the gastrointestinal dysfunction, showing that ANVS401 normalizes the colonic motility of both transgenic mouse models, while not affecting the Whole Gut Transit Time (WGTT). Pharmacokinetics studies revealed that ANVS401 is more abundant in the brain than in blood, in agreement with its lipophilicity, and the main metabolite is N8-NorPosiphen, a molecule with similar properties as ANVS401. The brain levels of ANVS401 necessary to effect optimal function were calculated in both studies and compared with efficacious brain levels from previous studies, showing that a 150 nM concentration of ANVS401 in the brain is sufficient for functional efficacy.
The PD study was funded by the Michael J. Fox Foundation.
PD is the second most common neurodegenerative disease after AD and affects the central, peripheral, and enteric nervous systems. Gastrointestinal dysfunction is a particularly common non-motor abnormality in PD, documented in over 80% of patients.
PD affects an estimated one million people in the U.S. and as many as 10 million globally. An estimated 5.8 million people in the U.S. have AD and there are approximately 44 million people worldwide living with the disease.
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