Annovis Bio, Inc. (NYSE: ANVS), a late-stage clinical drug platform company developing transformative therapies to treat neurodegenerative diseases, including Alzheimer’s Disease (AD) and Parkinson’s Disease (PD), presented three posters at the Alzheimer’s Association International Conference (AAIC) 2023 annual meeting held in Amsterdam, Netherlands, from July 16-20.

Overexpression of neurotoxic proteins disrupts axonal transport, the information highway of the nervous system, causing inflammation, loss of function, and nerve cell death - all hallmarks of a wide range of neurodegenerative diseases including AD and PD. Annovis’ drug acts through a novel mechanism of action that inhibits all the major neurotoxic proteins responsible for AD and PD even before they are produced. This contrasts with other companies’ AD and PD drugs which remove only one of the toxic proteins after it is produced.

The combined findings from the posters tell the story of an exceptionally promising treatment for neurodegenerative disease such as AD and PD. First, in a mouse model of AD buntanetap inhibits toxic proteins in the brain, improves axonal transport, lowers inflammation, and protects nerve cells from dying. This is associated with improved movement and cognition.

Second, these findings are replicated in all the human AD and PD phase I and II trials to date, with decreased toxic proteins in the brain, improved axonal transport, lowered inflammation, and protection of neurons from dying. In both mice and humans, not only has buntanetap been safe and very well tolerated, but it has also been effective in actually improving movement and cognition. In addition, there is evidence of a dose-response relationship in mice and in humans between the drug dose administered and the inhibition of the neurotoxic proteins.

Cheng Fang, Ph.D., senior vice president of research and development at Annovis Bio, presented two posters at AAIC. In the first - “Do Mouse Data Lie? For Buntanetap, They Totally Predict Human Outcome” - Annovis compared animal data with data from humans to see if the animal data were predictive of human outcomes. In their studies conducted to date on AD in mouse models and humans, they were able to reduce toxic protein production levels from disease levels down to normal levels. The researchers found consistently lowered levels of neurotoxic aggregating proteins and statistically significant improvements in cognition after buntanetap treatment.

In “Interim Analysis Results of Buntanetap in Phase III Clinical Studies in Alzheimer’s and Parkinson’s Disease,” which analyzed data from patients in both AD and PD phase II trials who received different doses of the drug, Annovis showed that buntanetap is safe, well-tolerated, and efficacious both in patients with AD and with PD. The interim analyses confirm that Annovis has the right sample size for clinical trials and support further development of buntanetap in phase III trials as a potential treatment for both AD and PD.

A third poster was presented by Don Elbert, Ph.D., associate professor of neurology, University of Washington School of Medicine, in collaboration with Annovis and the Alzheimer’s Disease Cooperative Study (ADCS). Titled “Stable Isotope Labelling Kinetics: Models and Methods to Evaluate APP Production Rates with Posiphen Treatment in the DISCOVER Clinical Trial,” the research sought to better describe buntanetap’s effect in humans on lowering the production of APP (amyloid precursor protein, a key toxic protein in the development of AD), to further assess the drug’s therapeutic potential.

These results showed evidence that buntanetap lowers the rate of production of APP, suggesting a dose-response relationship. For the design of future studies, the methodology is helpful for evaluating the body’s response to different doses of drug in terms of inhibition of production of APP and is important in determining the optimal dosage in future phase II and III trials.

“Together these results are exciting because they confirm buntanetap’s mechanism of action and that the drug is safe and effective,” said Dr. Fang. “Importantly, they further support buntanetap’s promise, as it continues to progress through clinical trials, as a future therapy for devastating neurodegenerative diseases like Alzheimer’s and Parkinson’s.”

Each year, the AAIC convenes the leading basic scientists, clinical researchers, clinicians, and the care research community to share breaking research in the study and treatment of AD.

About Annovis Bio, Inc.

Headquartered in Berwyn, Pennsylvania, Annovis Bio, Inc. is a late-stage clinical drug platform company developing transformative therapies that treat neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and other chronic and acute neurodegenerative diseases. The Company believes that it is the only company developing a drug that inhibits more than one neurotoxic protein, improves the information highway of the nerve cell, known as axonal transport, reduces inflammation and protects nerve cells from dying in chronic and acute neurodegeneration. Annovis conducted two Phase 2 studies: one in AD patients and one in both AD and PD patients. In the AD/PD study, buntanetap showed improvements in cognition and memory in AD as well as body and brain function in PD patients.

For more information on Annovis Bio, please visit the Company's website www.annovisbio.com and follow us on LinkedIn and Twitter.

Forward-Looking Statements

Statements in this press release contain "forward-looking statements" that are subject to substantial risks and uncertainties. Forward-looking statements contained in this press release may be identified by the use of words such as "anticipate," "expect," "believe," "will," "may," "should," "estimate," "project," "outlook," "forecast" or other similar words, and include, without limitation, statements regarding the timing, effectiveness, and anticipated results of buntanetap clinical trials. Forward-looking statements are based on Annovis Bio, Inc.'s current expectations and are subject to inherent uncertainties, risks and assumptions that are difficult to predict. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. These and other risks and uncertainties are described more fully in the section titled "Risk Factors" in the Annual Report on Form 10-K for the year ended December 31, 2021, filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information except as required under applicable law.

Laura Feragen Jacobson Strategic Health laura@jacobsonstrategic.com 267-262-4309

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