advax summary slide deck
TRANSCRIPT
2
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.
3
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.
4
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
5
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.
6
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
7
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.
8
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.
9
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
10
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.
11
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
13
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
14
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.
15
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.
16
AdVax, in partnership with BMI, has the exclusive technology to overcome deceptive imprinting.
How do Class II Pathogens Accomplish this Feat?
DECEPTIVE IMPRINTING
17
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.
18
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
19
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
20
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
21
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*
22
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