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Attacks Alzheimer’s Disease and
Neurodegeneration by Improving the
Information Highway of the Nerve Cell
Axonal Transport
M a y 2 0 2 1
Symbol: ANVS (NYSE American)
FORWARD-LOOKING STATEMENTS
Statements in this presentation contain “forward-looking statements” that are subject to
substantial risks and uncertainties. Forward-looking statements contained in this presentation
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 Annovis Bio, Inc.’s expectations regarding
projected timelines of clinical trials, and expectations regarding current or future 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, including the timing of clinical trials. 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, 2019 filed with the Securities
and Exchange Commission. Forward-looking statements contained in this presentation are
made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information
except as required under applicable law.
2
3
▪ Annovis is developing drugs for Alzheimer's (AD) and Parkinson's
disease (PD), including the orphan indication Alzheimer's in Down
Syndrome (AD-DS)
▪ Lead compound, ANVS401, is the only drug to improve axonal transport,
the information highway of the nerve cell, by attacking multiple
neurotoxic proteins
▪ Two phase 2a clinical trials:
▪ AD trial run by Alzheimer’s Disease Cooperative Study (ADCS)
▪ AD and PD trial
▪ Successful completion of phase 2a clinical trials will validate our
approach and allow start of two phase 3 studies
HIGHLIGHTS
A novel approach to treat neurodegeneration is desperately needed
THE STATE OF NEURODEGENERATIVE DISEASES
▪ 5.8 million people in the US and 44 million people worldwide
are estimated to suffer from AD
▪ PD affects an estimated one million people in the U.S. and
as many as 10 million globally
▪ Total costs of care for people with Alzheimer’s and other
dementias could top $1.1 trillion in 2050
▪ From 1998 to 2018 there were over 500 failed attempts at
developing Alzheimer's drugs, primarily focused on amyloid
plaque
▪ The sector needs to rethink dementia, develop new
approaches and create new drugs
4
CHANGE IN CAUSES OF DEATH FROM 2000 TO 2018
5
• Breast Cancer - 13%
• Colon Cancer - 21%
• Heart Disease - 21%
• Stroke - 24%
• HIV - 67%
• Parkinson’s + 84%
• Alzheimer’s + 112%
Chronic and acute brain insults lead to high levels of neurotoxic proteins,
to inflammation and neurodegeneration
Attacking one neurotoxic protein results in minimal effect
ANVS401 is the only drug to attack multiple neurotoxic proteins simultaneously
Amyloid β
AD / PD- Aβ Targeting Compounds
ANNOVIS’ DRUG ATTACKS MULTIPLE NEUROTOXIC PROTEINS
Tau
Tauopathies - AD - Tau Targeting Compounds
aSynuclein
PD / AD - aSYN Targeting Compounds
6
Activated Microglia = High Inflammation
PIPELINE
7
Therapy Diseases/Conditions PRE-CLINICAL IND PHASE I PHASE II PHASE III
AD
PD
AD-DS
FTD
CTE
TBI
Stroke
Advanced AD
Oral drug for
chronic indications
Injectable drug for acute
traumatic events
Oral drug for advanced
AD and dementia
8
CORPORATE PATENT ESTATE
Patent/Application Subject Matter Status Expiry
Provisional
ANVS401 to treat viral and bacterial infections
of the brain, including Covid19
Pending
2041
PCT
ANVS401 and 405 – Mechanism of Action
for prevention and treatment of diseases
Pending
2038
PCT ANVS405 - Acute brain and nerve injuries Granted – Europe and Japan 2036
PCT
ANVS401 - pK/pD, low doses, formulations
Neurodegenerative Diseases
Granted – US and Europe 2031
In-licensed
patents
Composition of matter, manufacturing,
method for treating AD and DS
Granted 2022-25
Composition
of Matter and
Method of Use 
Process for
Production 
Methods of Use:
pK/pD, Dose,
Formulations 
Method of Use:
Acute Brain
and Nerve
Injuries

Method of Use:
Prevention
and Treatment
Multi-layer strategy
NEUROTRANSITTERS
THAT TRAVEL ACCROSS
THE AXON
Adrenaline
Noradrenaline
Dopamine
HOW NERVE CELLS WORK
In healthy nerve cells little packages containing neurotransmitters or nerve growth factors
travel unimpaired from the cell body through the axon to the synapse.
SOMA &
CELL BODY
DENDRITES
Serotonin
Gaba
Acetylcholine
Glutamine
Endorphins
SYNAPSE
9
Neurotoxic proteins limit the flow and speed at which
neurotransmitters travel along the axon resulting
in compromised nerve function
T H E I N F O R M A T I O N H I G H W A Y
NEUROTOXIC PROTEINS IMPAIR AXONAL
TRANSPORT AND CAUSE A TOXIC CASCADE
ANVS401 IMPROVES AXONAL TRANSPORT
AND IMPEDES THE TOXIC CASCADE
IMPAIRED AXONAL TRANSPORT
SLOWER SYNAPTIC TRANSMISSION
INFLAMMATION
DEATH OF NERVE CELLS
LOSS OF COGNITIVE AND
MOTOR FUNCTION
IMPROVED AXONAL TRANSPORT
INCREASED SYNAPTIC TRANSMISSION
NO INFLAMMATION
HEALTHY NERVE CELLS
IMPROVED COGNITIVE AND
MOTOR FUNCTION
HIGH LEVELS OF NEUROTOXIC
PROTEINS
ANVS401 LOWERS LEVELS OF
NEUROTOXIC PROTEINS
11
RESULTS IN HUMANS
ANVS401 Lowers Neurotoxic Proteins in Cerebrospinal Fluid (CSF)
of Mild Cognitive Impaired (MCI) Patients
▪ In this proof-of-concept study, ANVS401 lowers the levels of APP/Aβ, tau/p-tau and
αSYN back to the levels seen in healthy volunteers
▪ It lowers the levels of the three neurotoxic proteins causing AD and PD
Maccecchini et al: JNNP 2012; 83: 894-902
NEURODEGENERATION IS AN AXONAL TRANSPORT DISEASE
Axonal transport is responsible for:
Normal Transport
The Normal Flow and Speed of vesicles carrying BDNF across the axon.
▪ Neurotransmitters GABA
(anxiety), ACh (cognition),
dopamine (movement),
serotonin (mood)
▪ Neurotrophic factors NGF,
BDNF
▪ All communication within
and between nerve cells
“Axonal transport disruption is
linked to human neurological
conditions.” - Nature Review, September 2019
Abnormal Transport
Shows the Blockage and Slowing of BDNF across the axon. Black areas demonstrate where
transport is slowed due to high levels of neurotoxic proteins.
TREATED WITH
The Flow and Speed of axonal transport is improved.
(120s)
(88s)
(88s)
APP, Ab42, C99 – Mobley, UCSD; aSYN – Isacson, Harvard; Lee, U.Penn;
Tau – U. Muenich & Zuerich; Htt – Mobley, UCSD; TDP43 – Taylor, Northwestern
Retrograde (0.5 frame/sec)
12
13
ANVS401 LOWERS INFLAMMATORY MARKERS
Maccecchini et al: JNNP 2012; 83: 894-902
CSF Inflammatory Markers Significantly
Decrease After 10 Days of Oral ANVS401 in
MCI Patients
Inflammatory
Protein
CSF % of
Baseline
p-Value
Complement C3 -86.9% 0.0007
MCP-1 -87.5% 0.0007
YKL40 -72.7% 0.0113
sCD14 -26.1% 0.1159
Factor FH* 23.7% 0.4988
* Control Factor
14
RESULTS IN ANIMALS
Multiple animal studies showed that ANVS401 improved the affected function
Function Animal Model
Memory and learning AD mice, DS mice, stroke mice, TBI rats
Movement PD mice, FTD mice
Eyesight Acute glaucoma rats
15
TWO PHASE 2 CLINICAL TRIALS
AD Trial AD / PD Trial
CRO ADCS Parexel
Therapeutic
Area
Early AD Early to Moderate AD and PD
Phase 2 2
Patients 24 28 + 40
Sites 6 12
Country United States
Design Double-Blind, Placebo-Controlled, Biomarker Study
Endpoints Reversal of Toxic Cascade
PHASE 2 CLINICAL TRIAL IN AD AND PD TO
MEASURE REVERSAL OF THE TOXIC CASCADE
AND IMPROVEMENT IN BRAIN FUNCTION
DECREASE IN NEUROTOXIC PROTEINS
INCREASE IN NEUROTRANSMITTERS
LOWERING OF INFLAMMATORY PROTEINS
LOWERING OF NEURODEGENERATION
MARKERS
COGNITION AND MOTOR FUNCTION
ENDPOINTS
TARGET:
PATHWAY:
EFFICACY:
TIMELINE OF PHASE 2 CLINICAL TRIAL IN AD and PD
Preliminary data commenced in 1Q2021
Start Up AD/PD Study
August
2020
May
2021
June
2021
17
A meeting with the FDA to discuss the data from the AD and the
PD study as well as from the chronic toxicology in rats and dogs
is projected for Fall of 2021
14 AD
14 PD 68
Patients
March
2021
REVERSAL OF TOXIC CASCADE EXPECTED
OUTCOME
ACTUAL OUTCOME
AD PD
Level of neurotoxic proteins
Axonal transport
Inflammation
Dead nerve cells
Control proteins 0
Efficacy: Motor function +
Efficacy: Cognition
REVERSAL OF TOXIC CASCADE
Preliminary data from first 14 PD patients
18
+++ p< 0.001 0 no change
++ p<0.01 - Opposite result from expected
+ p<0.05
+/- trend All rows for Parkinson’s disease will read out later and the same
outcomes will also read out for Alzheimer’s disease
EFFICACY IN PD PATIENTS – SPEED & COORDINATION
Preliminary data from first 14 PD patients
30
35
40
45
50
55
0 25
B A S E LINE V S 25 DA Y S
30
35
40
45
50
55
P LA C E BO ANVS401
P LA CE B O V S 401
0
0.5
1
1.5
2
2.5
3
0 25
Baseline vs 25 Days
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
placebo ANVS401
Placebo vs 401
Speed: Left the comparison between the treated group
with 80 mg/day of ANVS401 at baseline before treatment
and after 25 days on treatment in the rapid coding test.
At 25 days the speed is faster than at baseline and they
make fewer mistakes (p<0.04).
Right the comparison between the placebo group and
the treated group at 25 days. This graph shows that while
the placebo group gets slower, the treated group gets
faster (p< 0.04). The lower number shows worse
performance. 19
Coordination: Left - Comparison between treated at
baseline and at 25 days. The two scores are identical –
patients remain stable
Right, the comparison is made between the placebo
group and the treated group both at 25 days. The
placebo treated group shows a marked deterioration in
their motor complications compared to the ANVS401
treated group that was stable (p< 0.07). The lower
number shows better performance.
#
of
fields
coded
#
of
mistakes
1% 2%
4%
8%
16%
47%
60-65 65-70 70-75 75-80 80-85 85+
20
MARKET PROJECTIONS
Source: Alzheimer‘s Association 2014; Incidence of AD in Relation to Age
Increase in Incidence with Aging of Population
Annual sales potential for US and worldwide
are over $100 billion dollars
FINANCIAL HIGHLIGHTS
21
▪ Completed IPO in January 2020
▪ Cash balance provides runway to
early 2022
▪ NIH grants funding ADCS Phase 2a
trial in AD and chronic toxicology
study
▪ ~40% insider ownership
▪ Analyst coverage from ThinkEquity
and Maxim Group
Ticker NYSEAmerican: ANVS
Recent Price $22.14
52-Week Range $2.42-$35.00
Market Cap $154M
Shares Outstanding 6.9M
Float 4.4M
Cash (mrq) $5.6M
LT Debt (mrq) $0.0M
KEY DATA
Share price and market cap as of April 30, 2021
CHIEF EXECUTIVES AND CHIEF ADVISORS
Jeffrey Cummings, MD, Chief Medical Advisor
Dr. Cummings completed Neurology residency and a Fellowship in Behavioral Neurology at Boston University, Boston, Massachusetts.
US training was followed by a Research Fellowship in Neuropathology and Neuropsychiatry at the National Hospital for Nervous
Diseases, Queen Square, London, England. Dr. Cummings was formerly Professor of Neurology and Psychiatry at UCLA, director of the
Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, director of the Deane F. Johnson Center for Neurotherapeutics at
UCLA and director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Cleveland and Florida. He is past president
of the Behavioral Neurology Society and of the American Neuropsychiatric Association. Dr. Cummings has authored or edited 30
books and published nearly 600 peer-reviewed papers.
22
Maria L. Maccecchini, PhD Founder, President & CEO
Dr. Maccecchini founded Annovis in May 2008 to develop better therapeutics for Alzheimer’s, Parkinson’s and other
neurodegenerative diseases. Was partner and director of two angel groups, Robin Hood Ventures and MidAtlantic Angel Group;
Founder and CEO of Symphony Pharmaceuticals/Annovis a biotech company that sold in 2001 to Transgenomic; General Manager
of Bachem Bioscience, the US subsidiary of Bachem AG, Switzerland and Head Molecular Biology Mallinckrodt; Dr. Maccecchini did
one postdoc at Caltech and one at the Roche Institute of Immunology, her PhD in biochemistry is from the Biocenter of Basel with a
two-year visiting fellowship at The Rockefeller University.
Jeffrey McGroarty, CPA, MBA, Chief Financial Officer
Mr. McGroarty is a financial executive with experience in investor relations, working with analysts, creditors and financial institutions,
planning and analysis, capital allocation, SEC communications and reporting, accounting, acquisitions and turnarounds. He is
experienced in effectively managing complex projects, building professional relations and developing staff. Mr. McGroarty was
previously employed as CFO of Safeguard Scientifics, Interim Controller at Cephalon, Inc., Vice President-Financial Planning and
Analysis of Exide Technologies, Inc., and Senior Manager at PWC. His MBA is from the Wharton School of Business.
William Mobley, MD, PhD Chief Scientific Advisor
Distinguished Professor, Department of Neurosciences Florence Riford Chair for Alzheimer Research and Associate Dean for
Neurosciences Initiatives at UC San Diego. He is a member of the National Academy of Medicine. His research focuses on the
neurobiology of neurotrophic factor actions/signaling and on the hypothesis that malfunction of these mechanisms contribute to
neuronal dysfunction in developmental and age-related disorders of the neurosystem.
SCIENTIFIC ADVISORY BOARD
23
Sidney Strickland, PhD, Chairman
Vice President and Dean for Educational Affairs and
Research Professor, Patricia and John Rosenwald
Laboratory of Neurobiology and Genetics at
Rockefeller University. Dr. Strickland’s laboratory
investigates how dysfunction of the circulatory system
contributes to Alzheimer’s and other
neurodegenerative disorders. He will serve as the
Chairman of Annovis Bio’s SAB.
Jeffrey Cummings, MD
Dr. Cummings completed Neurology residency and a
Fellowship in Behavioral Neurology at Boston University,
Massachusetts. US training was followed by a Research
Fellowship in Neuropathology and Neuropsychiatry at
the National Hospital for Nervous Diseases, London,
England. Dr. Cummings was formerly Professor of
Neurology and Psychiatry, Director of Alzheimer’s
Disease Research and Director of the Center for
Neurotherapeutics at UCLA. He was Director of the
Cleveland Clinic Lou Ruvo Center for Brain Health in Las
Vegas, Cleveland and Florida.
William Mobley, MD, PhD
Dr. Mobley is Distinguished Professor, Department of
Neurosciences Florence Riford Chair for Alzheimer
Research and Associate Dean for Neurosciences
Initiatives at UC San Diego. He is a member of the
National Academy of Medicine. His research focuses
on the neurobiology of neurotrophic factor
actions/signaling and on the hypothesis that
malfunction of these mechanisms contribute to
neuronal dysfunction in developmental and age-
related disorders of the neurosystem.
Gregory Petsko, PhD
Dr. Petsko is a member of the National Academy of
Sciences, the National Academy of Medicine, the
American Academy of Arts and Sciences and the
American Philosophical Society. His research
interests are directed towards understanding
the biochemical bases of neurological diseases like
Alzheimer’s, Parkinson’s, and ALS discovering
treatments (especially by using structure-based
drug design), that could therapeutically affect
those biochemical targets, and seeing any resulting
drug candidates tested in humans. He has also
made key contributions to the field of protein
crystallography.
Rudolph E. Tanzi, PhD
Dr. Tanzi has published over 500 research papers
and has received the highest awards in his field,
including the Metropolitan Life Foundation Award,
Potamkin Prize, Ronald Reagan Award, Silver
Innovator Award, and many others. He was
named to TIME magazine’s list of TIME100 Most
Influential People in the World (2015), and
received the Smithsonian American Ingenuity
Award, the top national award for invention and
innovation. He co-authored the popular trade
books “Decoding Darkness”, New York Times
bestseller, “Super Brain”, and international
bestseller “Super Genes”.
24
Michael B. Hoffman
Chairman
Mr. Hoffman is the Founder and Managing Partner
of Stone Capital Partners, a private equity firm
focused on power and renewable energy. He was
Partner of Riverstone, senior managing director at
the Blackstone Group and managing director at
Smith Barney, Harris Upham & Co. He serves as
Chairman of Onconova, Annovis Bio, Curative and
is on the Board of Rockefeller University.
Claudine E. Bruck, PhD
Dr. Bruck is a pharmaceutical executive and
scientist with strong entrepreneurial drive. Exhibited
successes in building a therapeutic research unit
de novo and leading discovery and clinical
development of biological (vaccines,
biopharmaceuticals) and small molecule
medicines as well as an ophthalmic drug portfolio.
With creativity and a strong results-focus, she is
energized to challenge and lead teams. Extensive
Pharmaceutical industry experience spans drug
discovery and development across several
therapeutic areas.
Mark White
Mr. White is a biopharmaceutical executive with
global marketing, business development and
sales experience. Currently, he is an
independent consultant and a member of Robin
Hood Ventures, a Philadelphia based angel
investor group. Previously, Mr. White held senior
level roles at Pfizer in marketing and commercial
development, where he led the successful global
launches of Inspira, Revatio, Lyrica and Xeljanz. In
his last position, he was Vice President
Worldwide Marketing, with global responsibility
for new product development and in-line
marketing for Pfizer’s Inflammation
Therapeutic Area.
Maria L. Maccecchini, PhD
Executive Board Member
Dr. Maccecchini founded Annovis in May 2008 to
develop better therapeutics for Alzheimer’s,
Parkinson’s and other neurodegenerative diseases.
She was the Founder and CEO of Symphony
Pharmaceuticals/Annovis, a company focused on
protecting brain cells after stroke which was sold in
2001 to Transgenomic.
BOARD OF DIRECTORS
Reid S. McCarthy
Mr. McCarthy is experienced in corporate financial
management, operations and new venture
development. He was CFO of Topaz
Pharmaceuticals, Inc. until its sale in 2011 to Sanofi
Pasteur. He also served as CFO of JJ Haines &
Company, Inc. and provided consulting CFO
services to several life sciences companies. He has
been a founding executive of several venture
capital-backed companies which were
successfully sold.
INVESTMENT SUMMARY
A novel approach to treat neurodegeneration is desperately needed
▪ The markets for AD and PD drugs are in the multibillions of dollars
and growing
▪ Annovis has a novel approach to stop the course of AD and PD
▪ ANVS401 improves axonal transport and recovers the affected
function
▪ The successful completion of our Phase 2 clinical trials will
provide validation of our approach in two diseases and allow us
to move to Phase 3 trials
25
Improves THE FLOW of Axonal Transport
in Alzheimer’s Disease and
Neurodegeneration
CONTACT US
1055 Westlakes Drive
Suite 300
Berwyn, PA 19312
+1 (610) 727-3913
info@annovisbio.com
Investor Relations
Dave Gentry
CEO, RedChip Companies
+1 (407) 491-4498
dave@redchip.com
www.annovisbio.com
Symbol: ANVS (NYSE American)

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ANVS401 Improves Axonal Transport in Neurodegenerative Diseases

  • 1. Attacks Alzheimer’s Disease and Neurodegeneration by Improving the Information Highway of the Nerve Cell Axonal Transport M a y 2 0 2 1 Symbol: ANVS (NYSE American)
  • 2. FORWARD-LOOKING STATEMENTS Statements in this presentation contain “forward-looking statements” that are subject to substantial risks and uncertainties. Forward-looking statements contained in this presentation 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 Annovis Bio, Inc.’s expectations regarding projected timelines of clinical trials, and expectations regarding current or future 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, including the timing of clinical trials. 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, 2019 filed with the Securities and Exchange Commission. Forward-looking statements contained in this presentation are made as of this date, and Annovis Bio, Inc. undertakes no duty to update such information except as required under applicable law. 2
  • 3. 3 ▪ Annovis is developing drugs for Alzheimer's (AD) and Parkinson's disease (PD), including the orphan indication Alzheimer's in Down Syndrome (AD-DS) ▪ Lead compound, ANVS401, is the only drug to improve axonal transport, the information highway of the nerve cell, by attacking multiple neurotoxic proteins ▪ Two phase 2a clinical trials: ▪ AD trial run by Alzheimer’s Disease Cooperative Study (ADCS) ▪ AD and PD trial ▪ Successful completion of phase 2a clinical trials will validate our approach and allow start of two phase 3 studies HIGHLIGHTS A novel approach to treat neurodegeneration is desperately needed
  • 4. THE STATE OF NEURODEGENERATIVE DISEASES ▪ 5.8 million people in the US and 44 million people worldwide are estimated to suffer from AD ▪ PD affects an estimated one million people in the U.S. and as many as 10 million globally ▪ Total costs of care for people with Alzheimer’s and other dementias could top $1.1 trillion in 2050 ▪ From 1998 to 2018 there were over 500 failed attempts at developing Alzheimer's drugs, primarily focused on amyloid plaque ▪ The sector needs to rethink dementia, develop new approaches and create new drugs 4
  • 5. CHANGE IN CAUSES OF DEATH FROM 2000 TO 2018 5 • Breast Cancer - 13% • Colon Cancer - 21% • Heart Disease - 21% • Stroke - 24% • HIV - 67% • Parkinson’s + 84% • Alzheimer’s + 112%
  • 6. Chronic and acute brain insults lead to high levels of neurotoxic proteins, to inflammation and neurodegeneration Attacking one neurotoxic protein results in minimal effect ANVS401 is the only drug to attack multiple neurotoxic proteins simultaneously Amyloid β AD / PD- Aβ Targeting Compounds ANNOVIS’ DRUG ATTACKS MULTIPLE NEUROTOXIC PROTEINS Tau Tauopathies - AD - Tau Targeting Compounds aSynuclein PD / AD - aSYN Targeting Compounds 6 Activated Microglia = High Inflammation
  • 7. PIPELINE 7 Therapy Diseases/Conditions PRE-CLINICAL IND PHASE I PHASE II PHASE III AD PD AD-DS FTD CTE TBI Stroke Advanced AD Oral drug for chronic indications Injectable drug for acute traumatic events Oral drug for advanced AD and dementia
  • 8. 8 CORPORATE PATENT ESTATE Patent/Application Subject Matter Status Expiry Provisional ANVS401 to treat viral and bacterial infections of the brain, including Covid19 Pending 2041 PCT ANVS401 and 405 – Mechanism of Action for prevention and treatment of diseases Pending 2038 PCT ANVS405 - Acute brain and nerve injuries Granted – Europe and Japan 2036 PCT ANVS401 - pK/pD, low doses, formulations Neurodegenerative Diseases Granted – US and Europe 2031 In-licensed patents Composition of matter, manufacturing, method for treating AD and DS Granted 2022-25 Composition of Matter and Method of Use  Process for Production  Methods of Use: pK/pD, Dose, Formulations  Method of Use: Acute Brain and Nerve Injuries  Method of Use: Prevention and Treatment Multi-layer strategy
  • 9. NEUROTRANSITTERS THAT TRAVEL ACCROSS THE AXON Adrenaline Noradrenaline Dopamine HOW NERVE CELLS WORK In healthy nerve cells little packages containing neurotransmitters or nerve growth factors travel unimpaired from the cell body through the axon to the synapse. SOMA & CELL BODY DENDRITES Serotonin Gaba Acetylcholine Glutamine Endorphins SYNAPSE 9 Neurotoxic proteins limit the flow and speed at which neurotransmitters travel along the axon resulting in compromised nerve function T H E I N F O R M A T I O N H I G H W A Y
  • 10. NEUROTOXIC PROTEINS IMPAIR AXONAL TRANSPORT AND CAUSE A TOXIC CASCADE ANVS401 IMPROVES AXONAL TRANSPORT AND IMPEDES THE TOXIC CASCADE IMPAIRED AXONAL TRANSPORT SLOWER SYNAPTIC TRANSMISSION INFLAMMATION DEATH OF NERVE CELLS LOSS OF COGNITIVE AND MOTOR FUNCTION IMPROVED AXONAL TRANSPORT INCREASED SYNAPTIC TRANSMISSION NO INFLAMMATION HEALTHY NERVE CELLS IMPROVED COGNITIVE AND MOTOR FUNCTION HIGH LEVELS OF NEUROTOXIC PROTEINS ANVS401 LOWERS LEVELS OF NEUROTOXIC PROTEINS
  • 11. 11 RESULTS IN HUMANS ANVS401 Lowers Neurotoxic Proteins in Cerebrospinal Fluid (CSF) of Mild Cognitive Impaired (MCI) Patients ▪ In this proof-of-concept study, ANVS401 lowers the levels of APP/Aβ, tau/p-tau and αSYN back to the levels seen in healthy volunteers ▪ It lowers the levels of the three neurotoxic proteins causing AD and PD Maccecchini et al: JNNP 2012; 83: 894-902
  • 12. NEURODEGENERATION IS AN AXONAL TRANSPORT DISEASE Axonal transport is responsible for: Normal Transport The Normal Flow and Speed of vesicles carrying BDNF across the axon. ▪ Neurotransmitters GABA (anxiety), ACh (cognition), dopamine (movement), serotonin (mood) ▪ Neurotrophic factors NGF, BDNF ▪ All communication within and between nerve cells “Axonal transport disruption is linked to human neurological conditions.” - Nature Review, September 2019 Abnormal Transport Shows the Blockage and Slowing of BDNF across the axon. Black areas demonstrate where transport is slowed due to high levels of neurotoxic proteins. TREATED WITH The Flow and Speed of axonal transport is improved. (120s) (88s) (88s) APP, Ab42, C99 – Mobley, UCSD; aSYN – Isacson, Harvard; Lee, U.Penn; Tau – U. Muenich & Zuerich; Htt – Mobley, UCSD; TDP43 – Taylor, Northwestern Retrograde (0.5 frame/sec) 12
  • 13. 13 ANVS401 LOWERS INFLAMMATORY MARKERS Maccecchini et al: JNNP 2012; 83: 894-902 CSF Inflammatory Markers Significantly Decrease After 10 Days of Oral ANVS401 in MCI Patients Inflammatory Protein CSF % of Baseline p-Value Complement C3 -86.9% 0.0007 MCP-1 -87.5% 0.0007 YKL40 -72.7% 0.0113 sCD14 -26.1% 0.1159 Factor FH* 23.7% 0.4988 * Control Factor
  • 14. 14 RESULTS IN ANIMALS Multiple animal studies showed that ANVS401 improved the affected function Function Animal Model Memory and learning AD mice, DS mice, stroke mice, TBI rats Movement PD mice, FTD mice Eyesight Acute glaucoma rats
  • 15. 15 TWO PHASE 2 CLINICAL TRIALS AD Trial AD / PD Trial CRO ADCS Parexel Therapeutic Area Early AD Early to Moderate AD and PD Phase 2 2 Patients 24 28 + 40 Sites 6 12 Country United States Design Double-Blind, Placebo-Controlled, Biomarker Study Endpoints Reversal of Toxic Cascade
  • 16. PHASE 2 CLINICAL TRIAL IN AD AND PD TO MEASURE REVERSAL OF THE TOXIC CASCADE AND IMPROVEMENT IN BRAIN FUNCTION DECREASE IN NEUROTOXIC PROTEINS INCREASE IN NEUROTRANSMITTERS LOWERING OF INFLAMMATORY PROTEINS LOWERING OF NEURODEGENERATION MARKERS COGNITION AND MOTOR FUNCTION ENDPOINTS TARGET: PATHWAY: EFFICACY:
  • 17. TIMELINE OF PHASE 2 CLINICAL TRIAL IN AD and PD Preliminary data commenced in 1Q2021 Start Up AD/PD Study August 2020 May 2021 June 2021 17 A meeting with the FDA to discuss the data from the AD and the PD study as well as from the chronic toxicology in rats and dogs is projected for Fall of 2021 14 AD 14 PD 68 Patients March 2021
  • 18. REVERSAL OF TOXIC CASCADE EXPECTED OUTCOME ACTUAL OUTCOME AD PD Level of neurotoxic proteins Axonal transport Inflammation Dead nerve cells Control proteins 0 Efficacy: Motor function + Efficacy: Cognition REVERSAL OF TOXIC CASCADE Preliminary data from first 14 PD patients 18 +++ p< 0.001 0 no change ++ p<0.01 - Opposite result from expected + p<0.05 +/- trend All rows for Parkinson’s disease will read out later and the same outcomes will also read out for Alzheimer’s disease
  • 19. EFFICACY IN PD PATIENTS – SPEED & COORDINATION Preliminary data from first 14 PD patients 30 35 40 45 50 55 0 25 B A S E LINE V S 25 DA Y S 30 35 40 45 50 55 P LA C E BO ANVS401 P LA CE B O V S 401 0 0.5 1 1.5 2 2.5 3 0 25 Baseline vs 25 Days 0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 placebo ANVS401 Placebo vs 401 Speed: Left the comparison between the treated group with 80 mg/day of ANVS401 at baseline before treatment and after 25 days on treatment in the rapid coding test. At 25 days the speed is faster than at baseline and they make fewer mistakes (p<0.04). Right the comparison between the placebo group and the treated group at 25 days. This graph shows that while the placebo group gets slower, the treated group gets faster (p< 0.04). The lower number shows worse performance. 19 Coordination: Left - Comparison between treated at baseline and at 25 days. The two scores are identical – patients remain stable Right, the comparison is made between the placebo group and the treated group both at 25 days. The placebo treated group shows a marked deterioration in their motor complications compared to the ANVS401 treated group that was stable (p< 0.07). The lower number shows better performance. # of fields coded # of mistakes
  • 20. 1% 2% 4% 8% 16% 47% 60-65 65-70 70-75 75-80 80-85 85+ 20 MARKET PROJECTIONS Source: Alzheimer‘s Association 2014; Incidence of AD in Relation to Age Increase in Incidence with Aging of Population Annual sales potential for US and worldwide are over $100 billion dollars
  • 21. FINANCIAL HIGHLIGHTS 21 ▪ Completed IPO in January 2020 ▪ Cash balance provides runway to early 2022 ▪ NIH grants funding ADCS Phase 2a trial in AD and chronic toxicology study ▪ ~40% insider ownership ▪ Analyst coverage from ThinkEquity and Maxim Group Ticker NYSEAmerican: ANVS Recent Price $22.14 52-Week Range $2.42-$35.00 Market Cap $154M Shares Outstanding 6.9M Float 4.4M Cash (mrq) $5.6M LT Debt (mrq) $0.0M KEY DATA Share price and market cap as of April 30, 2021
  • 22. CHIEF EXECUTIVES AND CHIEF ADVISORS Jeffrey Cummings, MD, Chief Medical Advisor Dr. Cummings completed Neurology residency and a Fellowship in Behavioral Neurology at Boston University, Boston, Massachusetts. US training was followed by a Research Fellowship in Neuropathology and Neuropsychiatry at the National Hospital for Nervous Diseases, Queen Square, London, England. Dr. Cummings was formerly Professor of Neurology and Psychiatry at UCLA, director of the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, director of the Deane F. Johnson Center for Neurotherapeutics at UCLA and director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Cleveland and Florida. He is past president of the Behavioral Neurology Society and of the American Neuropsychiatric Association. Dr. Cummings has authored or edited 30 books and published nearly 600 peer-reviewed papers. 22 Maria L. Maccecchini, PhD Founder, President & CEO Dr. Maccecchini founded Annovis in May 2008 to develop better therapeutics for Alzheimer’s, Parkinson’s and other neurodegenerative diseases. Was partner and director of two angel groups, Robin Hood Ventures and MidAtlantic Angel Group; Founder and CEO of Symphony Pharmaceuticals/Annovis a biotech company that sold in 2001 to Transgenomic; General Manager of Bachem Bioscience, the US subsidiary of Bachem AG, Switzerland and Head Molecular Biology Mallinckrodt; Dr. Maccecchini did one postdoc at Caltech and one at the Roche Institute of Immunology, her PhD in biochemistry is from the Biocenter of Basel with a two-year visiting fellowship at The Rockefeller University. Jeffrey McGroarty, CPA, MBA, Chief Financial Officer Mr. McGroarty is a financial executive with experience in investor relations, working with analysts, creditors and financial institutions, planning and analysis, capital allocation, SEC communications and reporting, accounting, acquisitions and turnarounds. He is experienced in effectively managing complex projects, building professional relations and developing staff. Mr. McGroarty was previously employed as CFO of Safeguard Scientifics, Interim Controller at Cephalon, Inc., Vice President-Financial Planning and Analysis of Exide Technologies, Inc., and Senior Manager at PWC. His MBA is from the Wharton School of Business. William Mobley, MD, PhD Chief Scientific Advisor Distinguished Professor, Department of Neurosciences Florence Riford Chair for Alzheimer Research and Associate Dean for Neurosciences Initiatives at UC San Diego. He is a member of the National Academy of Medicine. His research focuses on the neurobiology of neurotrophic factor actions/signaling and on the hypothesis that malfunction of these mechanisms contribute to neuronal dysfunction in developmental and age-related disorders of the neurosystem.
  • 23. SCIENTIFIC ADVISORY BOARD 23 Sidney Strickland, PhD, Chairman Vice President and Dean for Educational Affairs and Research Professor, Patricia and John Rosenwald Laboratory of Neurobiology and Genetics at Rockefeller University. Dr. Strickland’s laboratory investigates how dysfunction of the circulatory system contributes to Alzheimer’s and other neurodegenerative disorders. He will serve as the Chairman of Annovis Bio’s SAB. Jeffrey Cummings, MD Dr. Cummings completed Neurology residency and a Fellowship in Behavioral Neurology at Boston University, Massachusetts. US training was followed by a Research Fellowship in Neuropathology and Neuropsychiatry at the National Hospital for Nervous Diseases, London, England. Dr. Cummings was formerly Professor of Neurology and Psychiatry, Director of Alzheimer’s Disease Research and Director of the Center for Neurotherapeutics at UCLA. He was Director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, Cleveland and Florida. William Mobley, MD, PhD Dr. Mobley is Distinguished Professor, Department of Neurosciences Florence Riford Chair for Alzheimer Research and Associate Dean for Neurosciences Initiatives at UC San Diego. He is a member of the National Academy of Medicine. His research focuses on the neurobiology of neurotrophic factor actions/signaling and on the hypothesis that malfunction of these mechanisms contribute to neuronal dysfunction in developmental and age- related disorders of the neurosystem. Gregory Petsko, PhD Dr. Petsko is a member of the National Academy of Sciences, the National Academy of Medicine, the American Academy of Arts and Sciences and the American Philosophical Society. His research interests are directed towards understanding the biochemical bases of neurological diseases like Alzheimer’s, Parkinson’s, and ALS discovering treatments (especially by using structure-based drug design), that could therapeutically affect those biochemical targets, and seeing any resulting drug candidates tested in humans. He has also made key contributions to the field of protein crystallography. Rudolph E. Tanzi, PhD Dr. Tanzi has published over 500 research papers and has received the highest awards in his field, including the Metropolitan Life Foundation Award, Potamkin Prize, Ronald Reagan Award, Silver Innovator Award, and many others. He was named to TIME magazine’s list of TIME100 Most Influential People in the World (2015), and received the Smithsonian American Ingenuity Award, the top national award for invention and innovation. He co-authored the popular trade books “Decoding Darkness”, New York Times bestseller, “Super Brain”, and international bestseller “Super Genes”.
  • 24. 24 Michael B. Hoffman Chairman Mr. Hoffman is the Founder and Managing Partner of Stone Capital Partners, a private equity firm focused on power and renewable energy. He was Partner of Riverstone, senior managing director at the Blackstone Group and managing director at Smith Barney, Harris Upham & Co. He serves as Chairman of Onconova, Annovis Bio, Curative and is on the Board of Rockefeller University. Claudine E. Bruck, PhD Dr. Bruck is a pharmaceutical executive and scientist with strong entrepreneurial drive. Exhibited successes in building a therapeutic research unit de novo and leading discovery and clinical development of biological (vaccines, biopharmaceuticals) and small molecule medicines as well as an ophthalmic drug portfolio. With creativity and a strong results-focus, she is energized to challenge and lead teams. Extensive Pharmaceutical industry experience spans drug discovery and development across several therapeutic areas. Mark White Mr. White is a biopharmaceutical executive with global marketing, business development and sales experience. Currently, he is an independent consultant and a member of Robin Hood Ventures, a Philadelphia based angel investor group. Previously, Mr. White held senior level roles at Pfizer in marketing and commercial development, where he led the successful global launches of Inspira, Revatio, Lyrica and Xeljanz. In his last position, he was Vice President Worldwide Marketing, with global responsibility for new product development and in-line marketing for Pfizer’s Inflammation Therapeutic Area. Maria L. Maccecchini, PhD Executive Board Member Dr. Maccecchini founded Annovis in May 2008 to develop better therapeutics for Alzheimer’s, Parkinson’s and other neurodegenerative diseases. She was the Founder and CEO of Symphony Pharmaceuticals/Annovis, a company focused on protecting brain cells after stroke which was sold in 2001 to Transgenomic. BOARD OF DIRECTORS Reid S. McCarthy Mr. McCarthy is experienced in corporate financial management, operations and new venture development. He was CFO of Topaz Pharmaceuticals, Inc. until its sale in 2011 to Sanofi Pasteur. He also served as CFO of JJ Haines & Company, Inc. and provided consulting CFO services to several life sciences companies. He has been a founding executive of several venture capital-backed companies which were successfully sold.
  • 25. INVESTMENT SUMMARY A novel approach to treat neurodegeneration is desperately needed ▪ The markets for AD and PD drugs are in the multibillions of dollars and growing ▪ Annovis has a novel approach to stop the course of AD and PD ▪ ANVS401 improves axonal transport and recovers the affected function ▪ The successful completion of our Phase 2 clinical trials will provide validation of our approach in two diseases and allow us to move to Phase 3 trials 25
  • 26. Improves THE FLOW of Axonal Transport in Alzheimer’s Disease and Neurodegeneration CONTACT US 1055 Westlakes Drive Suite 300 Berwyn, PA 19312 +1 (610) 727-3913 info@annovisbio.com Investor Relations Dave Gentry CEO, RedChip Companies +1 (407) 491-4498 dave@redchip.com www.annovisbio.com Symbol: ANVS (NYSE American)