Annovis Bio, Inc. (NYSE:ANVS) (“Annovis” or the “Company”), a late-stage clinical drug platform company addressing neurodegenerative diseases, today released the following letter to stockholders from its Chief Executive Officer Dr. Maria Maccecchini.
Dear Fellow Stockholder,
Over the years we have been talking about the potential of buntanetap to treat more than Alzheimer’s disease. In cell models, animal models and human clinical studies, we have seen that buntanetap works in numerous acute and chronic neurodegenerative conditions. I would like to take this opportunity to explain how one drug can be so broadly applicable.
Buntenatap works by inhibiting specific neurotoxic proteins such as amyloid precursor protein (APP), Tau, alpha-synuclein (αSYN), TAR DNA binding protein 43 (TDP-43), huntingtin (HTT) and prion protein. These proteins have normal functions but in their neurotoxic aggregating form, they impair axonal transport, slow synaptic transmission, cause inflammation, and ultimately, kill nerve cells, resulting in the loss of affected function in various neurodegenerative conditions.
The overexpression and aggregation of these proteins is caused by elevated levels of iron in the nerve cell. The mRNAs of neurotoxic aggregating proteins contain an iron response element (IRE) which binds to an iron regulatory protein called IRP1. At normal iron levels, translation occurs at appropriate physiological levels. When iron flows into the cell, the mRNAs are released and translated at higher rates by the ribosome. When massive iron flows in, the mRNAs remain unbound for as long as the iron is high and the proteins for these neurotoxic aggregating proteins are overexpressed. In this high iron situation, buntanetap binds to the atypical IRE-IRP1 complex and prevents the mRNA from being released and, therefore, from being translated and overexpressed.
Buntanetap is able to inhibit the translation of multiple neurotoxic proteins through this mechanism of action, and as a result has the potential to treat numerous acute and chronic neurodegenerative conditions that share this pathway. In mouse or rat models of Alzheimer’s, Parkinson’s, stroke, frontotemporal dementia, traumatic brain injury, glaucoma, and Down Syndrome, buntanetap has been shown to normalize the levels of these neurotoxic proteins and to restore function.
Most importantly, this has been demonstrated in human clinical trials. In our recent Phase 2 clinical trial in Alzheimer’s disease and Parkinson’s disease, treatment with buntanetap resulted in reduction of aggregating proteins and statistically significant improvement in motor function in Parkinson’s disease patients and cognition in Alzheimer’s disease patients.
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FUNCTION |
TEST |
SUBJECT |
|
ANIMALS |
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|
Memory, learning |
Mazes |
AD mice, DS mice, stroke mice, TBI rats |
|
Movement |
Colonic motility, grip strength |
PD mice, tau mice |
|
Vision |
Sight |
Glaucoma rats |
|
Infections |
Cell death |
P. Gingivalis mice, Covid mice |
|
HUMANS |
||
|
Cognition, memory, learning |
ADAScog11 |
Early AD patients |
|
Attention, thinking speed |
WAIS coding |
Early AD patients |
|
Movement, coordination |
MDS-UPDRS |
Early PD patients |
|
Movement speed |
WAIS coding |
Early PD patients |
|
Table 1: Summary of all animal and human study data. |
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We look forward to unlocking the full potential of buntanetap and addressing unmet needs across a range of acute and chronic neurological conditions.
Maria L. Maccecchini, Ph.D.,
Founder, President, CEO and Executive Board Member
