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“Microbiome-Sparing Solutions for Alzheimer’s & Cardiovascular Disease.”

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AdVax is...

Advax is developing first-of-kind vaccines and a new suite of diagnostics, therapeutics, and monoclonal antibodies in the multi-billion-dollar arena of

Alzheimer’s prevention and cure.

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AdVax Founders

Garth Ehrlich, PhD, FAAASSystemic Microbiology & GenomicsDeveloper of the Mucosal Biofilm Paradigm, Distributed Genome Hypothesis, & Rubric of Bacterial Plurality. Executive Director, Center for Genomic Sciences, Allegheny-Singer Research Institute.

Peter Nara, MSc, DVM, PhD, FAAASVaccinology

Discoverer, Deceptive ImprintingInventor, Immune Refocusing Technology.

CEO, President, Chairman & co-founder of Biological Mimetics, Inc.

Mentored by Jonas Salk

Daniel L. Sindelar, DMDPeriodontics & Oral Systemic BiologyCo-founder & recent president of the American Academy for Oral Systemic Health (AAOSH)Founder and director of Oral Genomics.Preceptorship in prevention of heart attacks, strokes, & diabetes

Judith Miklossy, MD, PhD, DScNeuropathology, Neurology, & Psychiatry

Founder & Director of the Alzheimer’s Prevention International Foundation

Director of the International Alzheimer’s Research Center in Switzerland.

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Scientific Advisory Board

Marc Penn, MD, PhD• Former Medical Director,

Cardiac ICU, Cleveland Clinic

• Former Director, Bakken Heart-Brain Institute

• Chief Medical Officer, Cleveland Heartlab

• Professor of Integrative Medical Sciences, Northeast Ohio Medical University

StJohn Crean, PhD• Executive Dean of

College of Clinical and Biomedical Sciences, University of Central Lancashire

• Robert Bradlaw advisor, Faculty of Dental Surgery at the Royal College of Surgeons of England

• Editor-in-Chief, Faculty Dental Journal

W. Sue T. Griffin, PhD• Editor-in-Chief, Journal

of Neuroinflammation• Dillard Professor & Vice

Chairman, Donald W. Reynolds Dept. of Geriatrics, University of Arkansas for Medical Sciences

• Director of Research, Geriatric Research, Education and Clinical Center, VAMC/CAVHS

Angela Kamer, DDS• Research Scientist, NYU

School of Medicine Center for Brain Health

• Associate Professor of Periodontology & Implant Dentistry, New York University

Sim K. Singhrao, PhD• Senior Research Fellow,

University of Central Lancashire School of Medicine & Dentistry

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Our Vision

NEXT-GENERATION SALIVARY DIAGNOSTICS to identify risk for Alzheimer’s disease, multiple cardiovascular diseases, and neurodegenerative diseases.

LICENSING AGREEMENTS utilizing AdVaxIP, co-developing therapeutics for Alzheimer’s disease, multiple cardiovascular diseases, and neurodegenerative diseases.

MICROBIOME-SPARING VACCINES for keystone pathogen strains directly involved in the pathogenesis of Alzheimer’s disease, multiple cardiovascular diseases, and neurodegenerative diseases.

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Recent Advances

Completed Phase I of Research & DevelopmentAdVax has identified the most virulent strains of a keystone pathogen.

Initiated Development of a First-in-Man DiagnosticFirst-of-kind salivary diagnostics performed by physicians to determine microbial burden & subsequent risk for inflammatory disease

Engineered IRT Mutations into Bacterial Targets (n= 2-4 targets with 5-10 IRT mutations per target)

Now an active member of the Alzheimer’s Association Small Company ConsortiumThe mission of the AASCC is to advance Alzheimer’s disease (AD) research and innovation in small, start-up biotechnology, diagnostic and contract research organizations

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Science & TechnologyAdVax has sequenced and developed supragenomemodeling for the most pathogenic strains of two unique pathogens of oral origin involved in the pathogenesis of Alzheimer’s and cardiovascular diseases:

• Treponema denticola

• Porphyromonas gingivalis

AdVax uses our existing patented technology, developing diagnostics, monoclonal antibodies, and first-in-man vaccines for P. gingivalis & T. denticola

AdVax, in partnership with BMI, brings market-leading technologies currently being used in advanced-stage development of a human rhinovirus vaccine.

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AdVax Science & Technology

AdVax has discovered that cardiovascular disease and neurodegenerative diseases such as Alzheimer's have a common pathogenic etiology:

Specific strains of P. gingivalis.

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Percentage of People with Pathogenic Bacteria Over Threshold

P. Gingivalis Infects…

40% 61% 70% 77%

Age <30

83%

Age 30-40

Age 40-50

Age 50-60

Age >60

Data accumulated from over 200,000 salivary diagnostic samples

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to P. gingivalis & T. denticola

The Body’s Response

WHEN THESE BACTERIA ARE IN THE MOUTH• Oral/systemic vascular and organ

inflammation• Chronic active/silent infection• Biofilm formation• Bleeding gums• Bone loss• Loose/lost teeth• Cavities

WHEN THESE BACTERIA ARE PRESENT IN THE HEART • Foam cells• Ox-LDL• hs-CRP• Lp-PLA2• MPO

WHEN THESE BACTERIA ARE PRESENT IN THE BRAIN• Focal and disseminated neuro-

inflammation• Amyloid beta/Tau activation• Broad slow cognitive decline• Pre-AD and Alzheimer’s

disease• Breakdown of BBB

A rubric of genetic inflammatory traits determines where and how the body

responds to these pathogens.

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Lifestyle Triggers

Traditional lifestyle triggers such as stress, nutritional deficiencies, diet, and sleep:

• Increase the systemic burden of P. gingivalis and T. denticola

• Decrease the host response to these pathogens

A person can have healthy looking gums, but still have a very high bioburden. This silent infection can have grave impacts systemically, in the absence of traditional signs of periodontal disease,

triggering both bacterial spread and inducing inflammation at distant sites resulting in Alzheimer’s disease, as well as a host of cardiovascular diseases. These relationships are not linear—

stress/cortisol, genetics, diet, and obstructive sleep apnea play confounding roles.

12MMP-9/TIMP-1 imbalance induced in human dendritic cells by Porphyromonas gingivalis.

Monocytes may be used as a vehicle for transporting PG. PG can stimulate cytokine production and survive in monocytes.

Microbial Hijacking of Complement–Toll-Like Receptor Crosstalk: Pathogens may not simply undermine complement or TLRs as separate entities, but may also exploit their crosstalk pathways.

Oral administration of P. gingivalis induces dysbiosis of gut microbiota and impairs barrier function leading to dissemination of enterobacteria to the liver

Copper exhibits antimicrobial activity against PG by reducing planktonic & biofilm growth & invasion of host epithelial cells.

Porphyromonas gingivalis Infection Reduces Regulatory T Cells in Infected Atherosclerosis Patients.

MMP-9/TIMP-1imbalance induced in human dendritic cells by Porphyromonas gingivalis. Blood-brain barrier dysfunction by regulation of the MMP-9/TIMP-1 balance.

PG exacerbates brain amyloid deposition and triggers brain inflammation, leading to enhanced cognitive impairment.

Immune-Altering & Manipulating

Microbiome-Disrupting

Immune response deposits Cu

Alters Regulatory T-Cells

Breaks Down Blood Brain Barrier

Initiates Neuroinflammation

Promotes Monocyte Migration by Activating MMP-9

Immune-Evading & Translocating

P. gingivalis

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P. gingivalis initiates neuroinflammatory diseases, specifically Alzheimer's

“The data from the human brains and that from the in vivo mouse study suggested specific associations of P. gingivalis with AD inflammatory pathology.”

“The keystone hypothesis of Hajishengallis et al. helps to explain the contribution that P. gingivalis may cause the early development of a neurodegenerative condition such as Alzheimer’s disease. In our view, P. gingivalis (highly virulent strains) access the CNS during healthy stages but only those individuals with inflammatory susceptibility traits are likely to develop progressive inflammatory component representing neurodegenerative disease processes.”

Sim K. Singhrao, Alice Harding, Sophie Poole, Lakshmyya Kesavalu, and StJohn Crean, “Porphyromonas gingivalis Periodontal Infection and Its Putative Links with Alzheimer’s Disease,” Mediators of Inflammation, vol. 2015, Article ID 137357, 10 pages, 2015. doi:10.1155/2015/137357

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Oral pathogens found at the site of beta amyloid deposits in 98% of Alzheimer’s brains and non-existent in all but7% of the non-

Alzheimer’s brains.

ORAL ORIGIN

OLFACTORY BULB(First sign of AD is loss of smell)

ENTORHINAL CORTEX(First site of AD destruction & AB)

Miklossy J. Alzheimer's disease - a neurospirochetosis. Analysis of the evidence following Koch's and Hill's criteria. J Neuroinflammation. 2011;8(1):90.

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AdVax Targets: Class II Pathogens

Class II pathogens are resistant to current vaccine and monoclonal antibody technologies due to their ability to use molecular decoys, mutate and exist in numerous strains

Vaccines are the only known medical product that can be given to prevent infection by Class II pathogens.

Unmet and completely open multi-Billiondollar markets exist for multiple pathogens.

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AdVax, in partnership with BMI, has the exclusive technology to overcome deceptive imprinting.

How do Class II Pathogens Accomplish this Feat?

DECEPTIVE IMPRINTING

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BMI holds background and genus species specific patents for target vaccine proteins in infectious diseases areas for humans and animal health.

BMI has exclusive worldwide license for Immune Refocusing Technology from the National Institutes of Health.

BMI and AdVax co-own new identified Red Complex oral pathogens

(Initial immune refocused P. gingivalis and T. denticola patents pending.)

Biological Mimetics, Inc.

AdVax Intellectual Propertyin Partnership with BMI

Biological Mimetics, Inc. (“BMI”) was formed in 1996 to commercialize innovative pharmaceutical products that will improve the quality of life and overall state of public health by combating resistant and emerging diseases in human and veterinary medicine.

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AdVax Solutions

6 mos. – 1 year

ORAL GENOMICS

2 years

DIAGNOSTICS & THERAPEUTICS

3-6 years

VACCINES

First-of-kind salivary diagnostics performed by physicians to determine

microbial burden & subsequent risk for

inflammatory disease

REVENUE:$25 - $50 million per year

Early detection & prevention of disease

Paradigm-changing diagnostics, medical

devices, and monoclonal antibody-based

therapeutics

REVENUE:$100 million/year

& a solution for prevention & early detection of Alzheimer’s disease

Next-generation prophylactic,

microbiome-sparing vaccines

REVENUE:$1 - 2 billion/year

& a cure for one cause of Alzheimer’s disease

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Vaccine, Nanobody, & Monoclonal Antibody Development Timeline

Acquisition of a broad array of clinical strains of each species

(N = 10) of periodontal pathogen associated with AD

Map IDNPE’s on bacterial targets (n=1-2 bacterial sp.)

Sequence a minimum of 20 strains of each periodontal

pathogen (N = 200)

Engineer IRT mutations into bacterial targets (n= 2-4

targets with5-10 IRT mutations per target)

Perform comparative genomics on each species

including supragenomemodeling, identify core

genes, identify core gene subset under immune

selection for each species

Express IRT bacterial proteins in commercially licensable systems/

Prepare recombinant proteins for at least 4

candidate core genes for each species and collect

human sera from AD and periodontal patients.

Immunogenicity studies in 2 lab animal species

Determine which of the candidate core proteins

react with human serum from patients with

periodontal disease creating an active target list

4 months 6 months 2 months 6 months 3 months

Quarter 1 Quarter 2 Quarter 3 Quarter 4

COMPLETED

Ehrlich DGH Studies – Sequencing & Molecular Cataloguing

Nara IRT Vaccine& Monoclonal Antibody Development

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Diagnostics Timeline

6 month time frame

TEST 1: SALIVARY DIAGNOSTICSFirst-of-kind salivary diagnostics performed by

physicians to determine microbial burden & subsequent risk for CVD, Alzheimer’s, RA, Diabetes,

Glaucoma, etc.

TEST 2: BUCCAL INFLAMMATORY TESTINGDetermines inflammatory risk for Alzheimer’s

disease.

MARKET-READY DIAGNOSTICS

RESEARCH & DEVELOPMENT

RESEARCH & DEVELOPMENT

COMPLETED

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Product Launch Timeline

Year 1 Year 2 Year 3 Year 4 Year 5 Year 6

Salivary Diagnostics & Advanced Inflammation Testing

Value Inflection PointSalivary Diagnostic Revenues

Value Inflection &Exit Point*

Animal Ready, First-in-Man Vaccines & mAb Therapeutics for AD & CVD causing pathogens.

First-in-Man Vaccines & mAb Therapeutics for AD & CVDcausing pathogens. Full body scan

for early detection of AD

Value Inflection & Exit Point*

Value Inflection & Exit Point*

Value Inflection & Exit Point*

*Capitalizing on existing relationships with Big Pharma

Value Inflection & Exit Point*

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Multiple exits: Phase 1, Phase 2a/2b

Value Inflection Points: Discovery, IND Filing, Phase 1, Phase 2

THE RETURN

Seed Bridge Funding: $500,000 MET

Series A Funding: $2-5M

Series B Funding: $10-15M

CAPITAL NEEDS

Series A/B funding opportunities are being sought for the company's financing of both the development of novel point of care diagnostics worth $100s of millions per year and monoclonal antibodies and vaccines worth

more than $1-2 billion per year.

INVESTMENT OPPORTUNITIES

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