Advaxis is developing a personalized neoepitope immunotherapy called ADXS-NEO to target mutations specific to a patient's cancer. Recent advances in genomics, immunotherapy, and cancer biology have enabled a new understanding of cancer as unique to each patient. ADXS-NEO uses DNA sequencing to identify tumor-specific mutations, engineers these neoepitopes into a bacterial vector, and administers this to activate the patient's immune system to target and eliminate the cancer. Advaxis has several clinical programs testing this approach across multiple cancer types with the goal of empowering each patient's immune system to fight their own unique form of cancer.

1. Company
Confiden,al
and
Proprietary
ADXS-NEO
Personalized
Neoepitope-Targeted
Immunotherapy for
Cancer
A convergence of technologies
to benefit individual patients
1
Precision/Personalized
Therapies
Canadian
Organiza,on
for
Rare
Diseases
Annual
Mee,ng
November
7,
2016

2. 2Company
Confiden,al
and
Proprietary
2015
Advaxis,
Inc.
|
www.advaxis.com
The Technologies
Immunotherapy of Cancer
• Immune Systems Role in Tumor Surveillance
• Understanding Immunologic Tolerance
• Manipulating Immunologic Controls
• Understanding Failures and Successes of Immunotherapy
Genomics Science
• Human Genome Project -1988-2003 (International Consortium)
• Molecular Biologic Understanding of Cell Functional Pathways
• High Throughput Massively Parallel DNA/RNA sequencing – Now accomplished in 4-7 days
Oncogenesis
• Why do cells become cancerous
• What drives tumor growth
• Why do people with the same cancer respond differently
• Why does resistance develop

3. 3Company
Confiden,al
and
Proprietary
2015
Advaxis,
Inc.
|
www.advaxis.com
The Convergence – A new understanding and treatment paradigm
What have we learned?
• The immune system is generally capable of eliminating cancers
• The best balance between efficacy and side effects may be immunotherapy
• Cancers succeed primarily because of a problem or misperception of immune surveillance / tolerance
• Immunologic activity can be manipulated by pharmaceuticals and/or vaccines
• Cancer growth is driven by inappropriate signaling within molecular pathways
• Cancer is caused by an accumulation of mutations, some in tumor growth “driver” genes (10-1000+)
• Cancer is comprised of a diverse population of variants (not identical cells)
• Even patients with the same cancer type harbor vastly different sets of mutations
• DNA sequencing technology is becoming practical, and allows complete understanding of a patients
own personal cancer at the genomic and bioinformatics level within a few days
• The DNA /RNA sequence of a patient’s own cancer is the ultimate personal biomarker

4. Immuno-Oncology – A History
• 1891 William Coley – Coley’s toxins cause tumor regression
• Inflammatory response to pathogens changes immune tolerance of tumor
• 1985 FDA approves Interferon alpha2b - Hairy Cell Leukemia
• Immune modulation of signaling increases immune resistance against cancer
• 1985 First report of IL-2 LAK adoptive immune therapy (Rosenberg)
• Autologous lymphocytes could be manipulated and cultivated ex-vivo as cancer treatment
• 1988 First Report of Clinical Response to IL-2 TIL treatment (Rosenberg)
• Specific enhancement of CTL’s with tumor reactivity (TILs) more effective
• Griffith et. al. J. NCI, 81:1709-1717. 1989 Indium 111 labeled TILS.
TILs were trafficking to tumors, but shutting down.
• 1992 Interleukin 2 approved – Metastatic Renal Cancer (1998 Melanoma)
• Agonism of IL-2 receptor stimulate T cell activation and proliferation
• 2010 FDA Approves Provenge – MCRPC
• Directing immune response via dendritic cells can improve survival
• 2011 FDA Approves Yervoy – Advanced Melanoma
• Blocking inhibitory checkpoint facilitates anti-tumor immunity
• 2011 First Report - CD-19 CAR-T in CLL (Carl June)
• 2014 FDA Approves Keytruda – Advanced Melanoma
4
~100 Yrs
Adoptive
Therapy
Meets
Tolerance
Tools
Immuno-Oncology
Renaissance
Tools
Therapeutic
Cancer
Vaccines

5. What makes the best immunotherapies effective?
• Checkpoint Inhibitors – Temporarily block mechanisms of immune tolerance
• Allows weak immune responses to progress
• CTLA4 – (Yervoy) Melanoma
• PD-1 / PD-L1 – Lung Cancer, Melanoma, Kidney, Head and Neck Cancer, Bladder
• Opdivo (BMS), Keytruda (Merck), Tecentriq (Roche)
• TIL Therapy, Rosenberg NCI (and others) – Cell Therapy
• Extract tumor fighting white blood cells from a patient, expand them in the lab, give them back to fight cancer.
5
The
Aha
Moment!
Expansion
of
pre-­‐exis;ng
Tcells
from
the
pa;ent,
that
target
protein
sequences
associated
with
muta;ons
=
“Neoepitopes”
are
responsible
for
long-­‐term
tumor
control

6. Company
Confiden,al
and
Proprietary
6
Company
Confiden,al
and
Proprietary
Mutational Burden by Tumor Type
• Best efficacy in Melanoma, Lung Cancer
• More Mutations = more chances to have immunogenic neoepitopes (when presented by tumors)
• Challenge: Tumors are poor antigen presenters, mostly “normal”
• Solution: Prospectively Immunize patients against their own neoepitopes with a
potent system that is highly immunogenic…. Personalized Neoepitope
Immunotherapy
Schumacher TN and Schreiber RD. Neoantigens in cancer immunotherapy. Science 2015; 348, 6230: 69-74.

7. 7
Advaxis – Personalized Neoepitope Immunotherapy
Parallel DNA sequencing
mutations identified
ADXS-NEO: Weakened
bacteria with neoepitopes
given to patient
Neoepitopes secreted in
antigen presenting cells
T cells find, destroy tumor
“cell to cell combat”
T cells activated to hunt
down neoepitope targets
Neoepitopes presented by
patient’s immune system
Neoepitope coding DNA
bioengineered into personalized
vector
Immune tolerance reduced
Biopsy
to
first
treatment
~
6-­‐8
weeks

8. 8
Summary
We now have the technology to understand each patient’s cancer at a genomic level
Essentially, every single patient’s cancer is unique with many mutations that cause malignancy
New tools used to control the immune system are making immunotherapy the backbone of new
cancer treatments wherever possible
When applied together, technologies can identify the mutations that cause a patient’s cancer, and
mobilize the patient’s immune system to those mutations for immune elimination
“Personalized Neoepitope Immunotherapy” uses the very mutations that cause cancer as it’s
“Achilles heel”, by training the immune system to target and eliminate the mutated cells
The battle against cancer is a personal one, involving “cell to cell” combat between immune fighter
cells and the cancer cells that are trying to evade and neutralize them
Essentially, every cancer patient has a “rare” disease, unique to them alone. However the best way
to fight it may be through empowering their own immune system to fight it.

9. COMPANY CONFIDENTIAL AND PROPRIETARYCOMPANY CONFIDENTIAL AND PROPRIETARY
Broad Clinical Pipeline Targeting Multiple Tumors
PRODUCT INDICATION PHASE 1 PHASE 2 PHASE 3 Partner
AXAL
CERVICAL CANCER†
M
AIM2CERV: Adjuvant Randomized vs Placebo Phase 3*
Metastatic: GOG 0265 Phase 2
C Metastatic: Combo with Durvalumab Phase 1/2
HPV+ HEAD AND NECK CANCER†
M Presurgical: Window of Opportunity – Mount Sinai Phase 2
ANAL CANCER†
M
RTOG: Adjuvant Randomized vs Control Phase 2/3
Adjuvant: Single Arm High Risk – Brown University (BrUOG) Phase 1/2
Metastatic (FAWCETT) Phase 2
ADXS-PSA
PROSTATE CANCER
C Metastatic: Combo with KEYTRUDA (pembrolizumab) Phase 1/2
ADXS-HER2
HER2-POSITIVE SOLID TUMORS (INCLUDING OSTEOSARCOMA†)
M
Metastatic: Single Arm Phase 1
Osteosarcoma Phase 2
C Combination M Monotherapy Active Planned
*Under FDA Special Protocol Assessment.
†Orphan Drug Designation.
All trademarks and logos are the property of their respective owners. 9

10. 305 College Road East
Princeton, NJ
www.advaxis.com
ir@Advaxis.com
Dr. Robert Petit
Chief Scientific Officer, EVP