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Annovis Bio CEO Maria Maccecchini Issues Letter to Stockholders MALVERN, Pa .

Key Takeaway: Annovis Bio, Inc. CEO Maria Maccecchini addressed stockholders regarding the company's recent Phase II/III trial results for its Alzheimer's treatment, which faced criticism leading to a decrease in share price. Despite the setback, Maccecchini highlighted the study's contribution to the design of future trials, including patient prescreening and a focus on early-stage Alzheimer's patients. The company remains dedicated to advancing its drug, buntanetap, for both Alzheimer's and Parkinson's diseases, aiming to improve patient outcomes.

Market Sentiment Analysis

POSITIVE FACTORS

  • The Phase II/III study provided valuable information for future trials.
  • Annovis plans to prescreen patients to confirm diagnosis for more accurate results.
  • The company remains committed to developing treatments for Alzheimer's and Parkinson's diseases.

CONCERNS & RISKS

  • Recent results from the Alzheimer's study were met with anger and disappointment from stakeholders.
  • There was a significant drop in the company's share price following the results.
  • The Phase II/III trial revealed challenges in achieving consistent results, particularly with moderate Alzheimer's patients.

Full Press Release Details

Annovis Bio CEO Maria Maccecchini Issues Letter
Pa. -- May 6, 2024 -- Annovis Bio, Inc. (NYSE: ANVS) ("Annovis" or the
"Company"), a clinical-stage drug platform company developing novel therapies for neurodegenerative diseases, announced that
Maria Maccecchini, Founder, President, and CEO of Annovis, issued a letter to stockholders providing a review of Phase II/III data from
its Alzheimer's study and sharing next steps.
The last few days have been
very difficult. I received a lot of emails and phone calls that often expressed anger, uncertainty, and disappointment. Additionally,
our results were questioned and criticized. This reaction not only caused a drastic drop in our share price, but, more importantly, it
saddened the Annovis team. We are determined to develop a drug that treats Alzheimer's (AD) and Parkinson's diseases (PD)
and makes the life of the afflicted people and their caretakers easier. However, every setback makes it harder to reach this goal.
At Annovis, we hold rigorous science, open communication, and transparency
seriously, and it is our responsibility to conduct a clinical study in conformance with FDA guidelines and to the highest standards possible.
In science, results are often less than perfect, but they pave the way for a better plan when designing and executing the next steps.
The Phase II/III study provided
us with valuable information for an improved Phase III pivotal trial. First, we will prescreen patients for plasma AD biomarkers to confirm
the diagnosis. Second, we will only enroll patients with early and mild Alzheimer's (MMSE 21-28), the subpopulation which showed
the highest level of improvement after buntanetap, as seen from our completed AD studies (Table 1).
Study AD patient # Patients Endpoint Duration Drug vs Baseline Drug vs Placebo
Phase IIa; 2021 MMSE 18-28 14 ADAS-Cog11 1 month -4.4 -3.2
Phase II/III; 2024 MMSE 21-24 90 ADAS-Cog11 3 months -3.3 -2.36
Phase II/III; 2024 MMSE 14-20 112 ADAS-Cog11 3 months -0.65 1.79
Table 1. Summary of cognitive
response to buntanetap at different disease stages measured in completed AD studies conducted by Annovis. The table clearly shows a strong
response in patients with early AD (MMSE 18-28 and MMSE 21-24), while in moderate AD patients (MMSE 14-20), the response is obscured by
high placebo effect.
goal of the Phase II/III trial was to learn about the breadth of our drug's efficacy and to obtain information for a pivotal disease-modifying
study. This goal was achieved. We believe that the FDA will accept buntanetap for symptomatic relief and will allow us to continue
with the next pivotal Phase III study for disease-modification.
Buntanetap (formerly known as Posiphen or ANVS401) attacks neurodegeneration
by inhibiting the formation of multiple neurotoxic proteins - amyloid beta, tau, alpha synuclein, and TDP43 - thereby improving synaptic
transmission, axonal transport and neuroinflammation. Dysregulation of these pathways has been shown to be the cause of nerve cell degeneration
and ultimately death. By attacking these pathways, buntanetap has the ability to reverse neurodegeneration in Alzheimer's, Parkinson's,
and other neurodegenerative diseases.
About Annovis Bio, Inc.
Headquartered in Malvern, Pennsylvania, Annovis Bio, Inc. is a clinical-stage,
drug platform company addressing neurodegeneration, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), and other
chronic neurodegenerative diseases. The company believes it is the only company developing a drug for both AD and PD designed to inhibit
more than one neurotoxic protein to restore axonal and synaptic activity. By improving brain function, the Company's goal is to
treat memory loss and dementia associated with AD as well as body and brain dysfunction associated with PD. For more information about
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended.
All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The Company advises
caution in reliance on forward-looking statements. Forward-looking statements include, without limitation, the Company's plans related
to clinical trials. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results to
differ materially from those implied by forward-looking statements, including regarding patient enrollment, the effectiveness of buntanetap
and the timing, effectiveness, and anticipated results of the Company's clinical trials evaluating the efficacy, safety, and tolerability
of buntanetap. See also additional risk factors set forth in the Company's periodic filings with the SEC, including, but not limited to,
those risks and uncertainties listed in the section entitled Risk Factors, in the Company's Annual Report on Form 10-K and Quarterly
Reports on Form 10-Q filed with the SEC. All forward-looking statements in this press release are based on information available to the
Company as of the date of this filing. The Company expressly disclaims any obligation to update or alter its forward-looking statements,
whether as a result of new information, future events or otherwise, except as required by applicable law.
Maria Maccecchini, Ph.D.

Frequently Asked Questions

What is the purpose of Annovis Bio's latest clinical studies?

Annovis Bio aims to develop therapies for Alzheimer's and Parkinson's diseases.

What are the next steps after the Phase II/III study?

Annovis will prescreen patients and focus on enrolling early Alzheimer's cases.

What is Buntanetap's mechanism of action?

Buntanetap inhibits neurotoxic proteins, improving brain functions and reducing degeneration.

How has Annovis Bio responded to recent criticism?

CEO Maria Maccecchini acknowledged shareholder concerns and emphasized commitment to transparency.

What are the cognitive improvements observed in the studies?

Early Alzheimer's patients showed significant cognitive response compared to baseline and placebo.

Last updated: May 6, 2024