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Attacks Alzheimer’s Disease and
Neurodegeneration by Improving the
Information Highway of the Nerve Cell
Axonal Transport
J u n e 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 that clinical trials may be delayed; that the data
reported herein is interim data, conclusions as to which may be superseded by subsequent data we expect to
receive in connection with Phase 2a trials and/or subsequent clinical trials; and that any anticipated meeting with or
presentation to the FDA may be delayed. 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, 2020 and other
reports 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 - in Phase 2a clinical trial, is the only
drug to improve cognition in AD and motor function in PD
patients, as recently announced
▪ ANVS401 reduced inflammation, in PD patients as recently
announced. Additional biomarker data to come.
▪ 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
Attacking one neurotoxic protein results in
minimal effect
ANVS401 is the only drug to attack multiple
neurotoxic proteins simultaneously
Aβ Targeting Compounds
Amyloid β
Alzheimer’s - Parkinson’s
ANNOVIS’ NEW APPROACH TO ATTACK AD AND PD
Chronic and acute brain insults lead to high levels of neurotoxic proteins, inflammation
and to neurodegeneration
Tau Targeting Compounds
Tau
Tauopathies - Alzheimer’s
aSYN Targeting Compounds
aSynuclein
Parkinson’s - Alzheimer’s
4
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
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
6
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
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)
7
8
RESULTS IN ANIMALS
Multiple animal studies showed that ANVS401 improved the affected function
Function Animal Model
Memory and learning (4) AD mice, DS mice, stroke mice, TBI rats
Movement (2) PD mice, FTD mice
Eyesight (1) Acute glaucoma rats
9
TWO PHASE 2 CLINICAL TRIALS
AD Trial PD Trial
CRO Parexel
Therapeutic
Area
Early to Moderate AD Early to Moderate PD
Phase 2 2
Patients 14 14 + 40
Sites 12 12
Country United States
Design
Double-Blind, Placebo-Controlled,
Biomarker Study
Endpoints Reversal of Toxic Cascade
TIMELINE OF PHASE 2 CLINICAL TRIAL IN AD and PD
Preliminary data commenced in 1Q2021
Start Up AD/PD Study
August
2020
June/July
2021
August
2021
10
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
AD & PD
Markers
AD&PD
Efficacy
Whole
Study
May
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: WAIS coding
Efficacy: Motor function
Efficacy: Cognition
REVERSAL OF TOXIC CASCADE
Data from first 14 AD and 14 PD patients
11
+++ p< 0.001
++ p<0.01
+ p<0.05
+/- trend
0 no change
- opposite result from expected
EFFICACY IN PD PATIENTS – SPEED & COORDINATION
Data from first 14 PD patients
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.
12
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.
* P<0.04
LOWERING OF INFLAMMATION IN PD PATIENTS
Data from first 14 PD patients
13
The trial measured
four inflammatory
markers that are
prevalent in the
brains of AD and of
PD patients.
Each of the
inflammatory
markers showed
statistically
significant
reduction after 25
days of treatment
with ANVS401
compared to
baseline.
Inflammatory
Marker
% Change
from Baseline p-Value
Complement
C3 -24.9 0.0072
YKL40 -22.9 0.0213
sTREM2 -28.2 0.0108
GFAp -34.6 0.000001
EFFICACY IN AD PATIENTS – ADAS-Cog11
Data from 14 AD patients
14
Within Data:
From baseline to 25 days in the
ANVS401-treated group, ADAS-Cog11
improved by 4.4 points, a statistically
significant improvement of 30%
(p<0.05).
Between Data:
ANVS401-treated group compared to
placebo group at 25 days showed an
improvement of 3.3 points, or 22% (p=
0.13).
This is the first double-blind, placebo-controlled study that shows cognitive
improvements in AD patients as measured by ADAS-Cog and functional
improvements in PD patients as measured by the Unified Parkinson's Disease
Rating Scale (UPDRS).
CODING TEST SHOWS SIMILAR IMPROVEMENT IN AD AND
PD PATIENTS
15
The WAIS coding test measures speed in movement and thinking. Treated AD patients show
a 6.6 point and PD patients a 6.1-point improvement in coding after ANVS401 treatment.
1% 2%
4%
8%
16%
47%
60-65 65-70 70-75 75-80 80-85 85+
16
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
17
▪ Completed $50M equity raise in
May 2021
▪ Fully funded through anticipated
Phase 3 trial / two years
▪ NIH grants funding ADCS Phase 2a
trial in AD and chronic toxicology
study
▪ ~38% insider ownership
▪ Analyst coverage from ThinkEquity
and Maxim Group
Ticker NYSEAmerican: ANVS
Recent Price $48.73
52-Week Range $3.83 - $97.97
Market Cap $387M
Shares Outstanding 7.9M
Float 5.4M
Cash $50M
LT Debt $0.0M
KEY DATA
Share price, market cap, cash & debt as of May 26,
2021
MANAGEMENT AND ADVISORY TEAM
Cheng Fang, PhD, VP of Research
Dr. Fang is an experienced neuroscientist with more than a decade of experience in neurodegenerative diseases, with broad
scientific knowledge and hands-on experience. Prior to joining Annovis, she was a scientific solution consultant with Clarivate
Analytics where she worked on cutting-edge scientific projects with top-50 pharma clients. Previously, Dr. Fang was business
development manager for Coriell Institute for Medical Research and an assistant professor at Boston University, where she designed
and supervised projects focused on prion diseases and AD as a research team leader.
18
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
19
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.
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”.
20
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.
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 AD and PD
▪ ANVS401 shows statistically significant improvements in
Phase 2a clinical trials:
- Cognition in AD patients
- Motor function in PD patients
- WAIS coding in AD and PD patients
- Inflammation in PD patients
▪ The successful completion of our Phase 2 clinical trials is
providing validation of our approach in two diseases and
allow us to move to Phase 3 trials in both diseases 21
CHANGE IN CAUSES OF DEATH FROM 2000 TO 2018
22
• 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
23
Activated Microglia = High Inflammation
PIPELINE
24
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
25
CORPORATE PATENT ESTATE
Patent/Application Subject Matter Status Expiry
Provisional
ANVS401 to treat viral and bacterial infections
of the brain, including Covid19
Pending
2042
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
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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Annovis Presentation - June 2021

  • 1. Attacks Alzheimer’s Disease and Neurodegeneration by Improving the Information Highway of the Nerve Cell Axonal Transport J u n e 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 that clinical trials may be delayed; that the data reported herein is interim data, conclusions as to which may be superseded by subsequent data we expect to receive in connection with Phase 2a trials and/or subsequent clinical trials; and that any anticipated meeting with or presentation to the FDA may be delayed. 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, 2020 and other reports 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 - in Phase 2a clinical trial, is the only drug to improve cognition in AD and motor function in PD patients, as recently announced ▪ ANVS401 reduced inflammation, in PD patients as recently announced. Additional biomarker data to come. ▪ 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. Attacking one neurotoxic protein results in minimal effect ANVS401 is the only drug to attack multiple neurotoxic proteins simultaneously Aβ Targeting Compounds Amyloid β Alzheimer’s - Parkinson’s ANNOVIS’ NEW APPROACH TO ATTACK AD AND PD Chronic and acute brain insults lead to high levels of neurotoxic proteins, inflammation and to neurodegeneration Tau Targeting Compounds Tau Tauopathies - Alzheimer’s aSYN Targeting Compounds aSynuclein Parkinson’s - Alzheimer’s 4
  • 5. 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
  • 6. 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 6 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
  • 7. 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) 7
  • 8. 8 RESULTS IN ANIMALS Multiple animal studies showed that ANVS401 improved the affected function Function Animal Model Memory and learning (4) AD mice, DS mice, stroke mice, TBI rats Movement (2) PD mice, FTD mice Eyesight (1) Acute glaucoma rats
  • 9. 9 TWO PHASE 2 CLINICAL TRIALS AD Trial PD Trial CRO Parexel Therapeutic Area Early to Moderate AD Early to Moderate PD Phase 2 2 Patients 14 14 + 40 Sites 12 12 Country United States Design Double-Blind, Placebo-Controlled, Biomarker Study Endpoints Reversal of Toxic Cascade
  • 10. TIMELINE OF PHASE 2 CLINICAL TRIAL IN AD and PD Preliminary data commenced in 1Q2021 Start Up AD/PD Study August 2020 June/July 2021 August 2021 10 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 AD & PD Markers AD&PD Efficacy Whole Study May 2021
  • 11. REVERSAL OF TOXIC CASCADE EXPECTED OUTCOME ACTUAL OUTCOME AD PD Level of neurotoxic proteins Axonal transport Inflammation Dead nerve cells Control proteins 0 Efficacy: WAIS coding Efficacy: Motor function Efficacy: Cognition REVERSAL OF TOXIC CASCADE Data from first 14 AD and 14 PD patients 11 +++ p< 0.001 ++ p<0.01 + p<0.05 +/- trend 0 no change - opposite result from expected
  • 12. EFFICACY IN PD PATIENTS – SPEED & COORDINATION Data from first 14 PD patients 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. 12 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. * P<0.04
  • 13. LOWERING OF INFLAMMATION IN PD PATIENTS Data from first 14 PD patients 13 The trial measured four inflammatory markers that are prevalent in the brains of AD and of PD patients. Each of the inflammatory markers showed statistically significant reduction after 25 days of treatment with ANVS401 compared to baseline. Inflammatory Marker % Change from Baseline p-Value Complement C3 -24.9 0.0072 YKL40 -22.9 0.0213 sTREM2 -28.2 0.0108 GFAp -34.6 0.000001
  • 14. EFFICACY IN AD PATIENTS – ADAS-Cog11 Data from 14 AD patients 14 Within Data: From baseline to 25 days in the ANVS401-treated group, ADAS-Cog11 improved by 4.4 points, a statistically significant improvement of 30% (p<0.05). Between Data: ANVS401-treated group compared to placebo group at 25 days showed an improvement of 3.3 points, or 22% (p= 0.13). This is the first double-blind, placebo-controlled study that shows cognitive improvements in AD patients as measured by ADAS-Cog and functional improvements in PD patients as measured by the Unified Parkinson's Disease Rating Scale (UPDRS).
  • 15. CODING TEST SHOWS SIMILAR IMPROVEMENT IN AD AND PD PATIENTS 15 The WAIS coding test measures speed in movement and thinking. Treated AD patients show a 6.6 point and PD patients a 6.1-point improvement in coding after ANVS401 treatment.
  • 16. 1% 2% 4% 8% 16% 47% 60-65 65-70 70-75 75-80 80-85 85+ 16 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
  • 17. FINANCIAL HIGHLIGHTS 17 ▪ Completed $50M equity raise in May 2021 ▪ Fully funded through anticipated Phase 3 trial / two years ▪ NIH grants funding ADCS Phase 2a trial in AD and chronic toxicology study ▪ ~38% insider ownership ▪ Analyst coverage from ThinkEquity and Maxim Group Ticker NYSEAmerican: ANVS Recent Price $48.73 52-Week Range $3.83 - $97.97 Market Cap $387M Shares Outstanding 7.9M Float 5.4M Cash $50M LT Debt $0.0M KEY DATA Share price, market cap, cash & debt as of May 26, 2021
  • 18. MANAGEMENT AND ADVISORY TEAM Cheng Fang, PhD, VP of Research Dr. Fang is an experienced neuroscientist with more than a decade of experience in neurodegenerative diseases, with broad scientific knowledge and hands-on experience. Prior to joining Annovis, she was a scientific solution consultant with Clarivate Analytics where she worked on cutting-edge scientific projects with top-50 pharma clients. Previously, Dr. Fang was business development manager for Coriell Institute for Medical Research and an assistant professor at Boston University, where she designed and supervised projects focused on prion diseases and AD as a research team leader. 18 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.
  • 19. SCIENTIFIC ADVISORY BOARD 19 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. 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”.
  • 20. 20 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.
  • 21. 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 AD and PD ▪ ANVS401 shows statistically significant improvements in Phase 2a clinical trials: - Cognition in AD patients - Motor function in PD patients - WAIS coding in AD and PD patients - Inflammation in PD patients ▪ The successful completion of our Phase 2 clinical trials is providing validation of our approach in two diseases and allow us to move to Phase 3 trials in both diseases 21
  • 22. CHANGE IN CAUSES OF DEATH FROM 2000 TO 2018 22 • Breast Cancer - 13% • Colon Cancer - 21% • Heart Disease - 21% • Stroke - 24% • HIV - 67% • Parkinson’s + 84% • Alzheimer’s + 112%
  • 23. 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 23 Activated Microglia = High Inflammation
  • 24. PIPELINE 24 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
  • 25. 25 CORPORATE PATENT ESTATE Patent/Application Subject Matter Status Expiry Provisional ANVS401 to treat viral and bacterial infections of the brain, including Covid19 Pending 2042 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
  • 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)