Issuer Free Writing Prospectus
Filed Pursuant to Rule 433
Registration No. 333-201731
January 28, 2015
Opexa Therapeutics, Inc.
NASDAQ: OPXA
January 2015
The Woodlands, TX
Precision Immunotherapy
®	

	

2
Free Writing Prospectus Statement
•
This
presentation
highlights
basic
information
about
us
and
the
offering.
Being
a
summary
document,
this
slide
deck
does
not
contain
all
the
information
that
you
should
consider
before
investing.
•
We
have
filed
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statement
(including
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preliminary
prospectus)
with
the
SEC
for
the
offering
to
which
this
presentation
relates.
The
registration
statement
has
not
yet
become
effective.
Before
you
invest,
you
should
read
the
preliminary
prospectus
in
the
registration
statement
(including
the
risk
factors
described
therein)
and
other
documents,
including
the
Company's
Form
10-Ks
and
Form
10-Qs,
that
we
have
filed
with
the
SEC
for
more
complete
information
about
us
and
the
offering.
You
may
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by
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EDGAR”
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site
at
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The
preliminary
prospectus,
dated
January
28,
2015,
is
available
on
the
SEC
website.
Alternatively,
we
or
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this
offering,
Maxim
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LLC
and
National
Securities
Corporation,
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York,
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Telephone:
(212)-895-3745;
Email:
syndicate@maximgrp.com.	

	

3
Forward-Looking Statements
All
statements
in
this
presentation
other
than
those
of
historical
fact,
including
statements
regarding
our
preclinical
and
clinical
development
plans
for
Tcelna®
and
OPX-212,
our
research
and
other
development
programs,
our
ability
to
undertake
certain
activities
and
accomplish
certain
goals,
projected
timelines
for
our
research
and
development
activities
and
possible
regulatory
approvals,
if
any,
our
expectations
regarding
the
relative
benefits
of
our
product
candidates
versus
competitive
therapies,
our
expectations
regarding
the
possibility
of
licensing
or
collaborating
with
third
parties
regarding
our
product
candidates
or
research,
and
our
expectations
regarding
the
therapeutic
and
commercial
potential
of
our
product
candidates,
research,
technologies
and
intellectual
property,
are
forward-looking
statements.
The
words
“believe,”
“may,”
“will,”
“estimate,”
“continue,”
“anticipate,”
“design,”
“intend,”
“expect,”
“potential”
and
similar
expressions,
as
well
as
the
negative
version
of
these
words
and
similar
expressions,
are
intended
to
identify
forward-looking
statements.
Our
forward-looking
statements
do
not
constitute
guarantees
of
future
performance,
and
are
subject
to
a
number
of
risks
and
uncertainties
that
could
cause
actual
results
to
differ
materially
and
adversely
from
those
anticipated
or
implied
in
such
statements.
Our
forward-looking
statements
are
based
upon
our
current
expectations
and
involve
assumptions
that
may
never
materialize
or
may
prove
to
be
incorrect.
Actual
results
and
the
timing
of
events
could
differ
materially
from
those
anticipated
as
a
result
of
various
risks
and
uncertainties
which
include,
without
limitation,
risks
associated
with
the
process
of
discovering,
developing
and
commercializing
drugs
that
are
safe
and
effective
for
use
as
human
therapeutics
and
risks
inherent
in
the
effort
to
build
a
business
around
such
drugs.
Although
we
believe
our
expectations
are
reasonable,
we
do
not
in
any
way
guarantee
future
results,
level
of
activity,
performance
or
achievements.
In
addition,
neither
we
nor
any
other
person
assumes
responsibility
for
the
accuracy
and
completeness
of
any
forward-looking
statements.
Our
forward-looking
statements
in
this
presentation
speak
only
as
of
the
date
this
presentation
is
actually
delivered
by
us
in
person.
We
assume
no
obligation
or
undertaking
to
update
or
revise
any
statements
to
reflect
any
changes
in
our
expectations
or
any
change
in
events,
conditions
or
circumstances
on
which
any
such
statement
is
based.
You
should,
however,
review
additional
disclosures
we
make
that
further
describe
risks
and
uncertainties
relevant
to
us
in
additional
detail
in
our
filings
with
the
Securities
and
Exchange
Commission,
including
our
registration
statement
on
Form
S-1
initially
filed
on
January
28,
2015,
as
well
as
in
our
Annual
Report
on
Form
10-K,
Quarterly
Reports
on
Form
10-Q
and
Current
Reports
on
Form
8-K.
You
may
get
these
documents
for
free
by
visiting
EDGAR
on
the
SEC
web
site
at
http://www.sec.gov .	

	

4
Opexa Investment Highlights
PIPELINE
•
Tcelna
®
: Phase 2b for secondary progressive multiple sclerosis (SPMS), limited
competition, $7BN overall market potential, encouraging prior trials (Phase IIb RRMS,
Phase I/II SPMS)
•
OPX-212: Pre-IND for neuromyelitis optica (NMO), no approved therapies, orphan
indication
TECHNOLOGY
VALIDATION
•
Precision immunotherapy for T-cell-mediated autoimmune diseases
•
Proprietary Platform: potential to yield multiple candidates personalized to each patient
•
Company owned and scalable cGMP manufacturing facility
•
Strong patent estate (98 domestic and international)
•
Option
agreement
secured
with
Merck
Serono
for
Tcelna
–
strong
potential
partner
•
FDA Fast Track designation for Tcelna in SPMS
•
Esteemed Scientific Advisory Board	

	

5
Offering Summary
Issuer
Exchange/Ticker
Structure
Offering size
Subscription Price
Warrant structure
Oversubscription privilege
Use of proceeds
Co-managers
Opexa Therapeutics, Inc.
NASDAQ / OPXA
Rights Offering
Up to 28,776,419 Units
Each Unit composed of one share of common stock and one warrant
TBD
Range expected $0.65-$0.75
Exercise price: $0.50 per share from issuance through June 30, 2016; $1.50 per share from
July 1, 2016 through 3-year expiration
Redeemable for $0.01 per share upon certain conditions
Exercisable for cash unless no effective registration statement
Allocated pro rata up to available Units not purchased by other
holders, subject to limitations
Funding of ongoing Phase IIb Abili-T study in SPMS patients
Funding of preclinical and/or clinical development for OPX-212 in NMO
For general corporate purposes and operational purposes
Maxim Group
National Securities Corp.	

	

6
Opexa Investment Thesis
Why a Rights Offering?
•
A successful rights offering would give Opexa sufficient capital
to fund operations through 2016.
–
Complete
the
ongoing
Phase
2b
clinical
trial
in
SPMS
and
release
data
–
Potentially initiate a Phase 1/2 trial with OPX-212 in neuromyelitis optica (NMO)
Background
•
Opexa has previously raised over $90 million, with most being invested in its T-cell immunotherapy platform.
•
Opexa has conducted two Phase 1 trials and is currently conducting its second Phase 2 trial having treated both RRMS
and SPMS patients with Tcelna. Over 400 individuals in total have been enrolled in Opexa’s clinical trials for Tcelna,
including the ongoing Phase 2b SPMS trial.
•
Current Phase 2b trial is designed to show whether Tcelna could improve clinical outcomes -
data expected in 2H 2016.
–
Enrollment of 190 patients in a randomized, placebo-controlled trial completed
–
The Company may apply for accelerated approval and breakthrough designation with the FDA following the completion of the
current
Phase
2b
trial
in
the
event
of
positive
results
(primary
endpoint-whole
brain
atrophy;
secondary-progression)
•
Fast Track Designation obtained from the U.S. FDA for Tcelna in SPMS.
•
In addition, the Company has further leveraged its platform to move into neuromyelitis optica (NMO), an orphan (rare)
disease with no FDA-approved treatments. This program is in the pre-IND stage.
•
Immunotherapy approaches have been validated and are increasingly being applied in oncology.
•
Opexa has been refining its approach for over a decade focusing on autoimmune diseases, specifically, Tcelna for MS.
•
Based, in part, on
data generated in prior MS trials, Merck Serono, a leading pharma company in MS, entered into an
option and license agreement with Opexa to potentially license Tcelna for MS, worldwide, excluding Japan. Should
Merck Serono exercise its option, they would fund any future Phase III studies and commercial activities with potential
milestone payments and royalties coming to Opexa upon success of
the program.	

	

HOW DOES TCELNA WORK?
7	

	

8
The Root Cause of Multiple Sclerosis
Adapted by permission from Macmillan Publishers Ltd:  NATURE REVIEWS
IMMUNOLOGY 3, 483-492 (June 2003), copyright (2003)
Cytokines
Damage
Damage
•
MS is an inflammatory disease in which the
insulating cover of the nerve fibers (the
myelin sheath) in the brain are damaged by
the body’s own immune system. There is no
cure for MS.
•
In MS patients, the faulty immune system is
unable to prevent the attack of myelin
reactive T-cells (MRTC)
•
MRTC cross the blood brain barrier, enter
the brain leading to a two pronged attack
through:
1.
Destruction of myelin sheath, the protective
coating of nerve fibers
2.
Destruction of oligodendroglial cells, which
are responsible for producing myelin
Myelin peptide
Activated T-
cells degrade Myelin and
Damage Myelin Producing  Cells	

	

9
Tcelna Could Address the Root Cause of Multiple Sclerosis by
Preventing Demyelination and Enabling Remyelination
Adapted by permission from Macmillan Publishers Ltd:  NATURE REVIEWS
IMMUNOLOGY 3, 483-492 (June 2003), copyright (2003)
Opexa’s Strategy
Tcelna programs the immune system to
specifically
recognize only the damaging T-
cells (MRTC), thereby inhibiting further
destruction of the myelin sheath and
potentially enabling remyelination
•
Immune cells, including Tregs, have been
primed, or sensitized to specifically target
the pathogenic MRTC for elimination or
regulation
•
Elimination of harmful MRTC may lead to:
o
Stabilization of disease by preventing
further destruction of myelin
o
Improvement in condition by allowing
Oligondendroglial cells to remyelinate
axons (neuroprotection)	

	

RESULTS AND EXPLANATION OF RRMS &
RESULTS AND EXPLANATION OF RRMS &
SPMS CLINICAL TRIALS
SPMS CLINICAL TRIALS
10	

	

11
Business Strategy and Rationale for Pursuing
Secondary Progressive MS (SPMS)
•
Opexa
completed
a
Phase
2b
clinical
study
in
RRMS
patients
–
Although the primary MRI endpoint was not met, the clinical signal was encouraging
–
In a subset of more active RRMS subjects, patients treated with Tcelna saw a statistically
significant improvement in disability, and the therapy was safe and well tolerated
–
Opexa completed formal End of Phase 2 meetings with the FDA and obtained support to move
into Phase 3 studies in RRMS
•
In
separate
Phase
I/II
trials
in
SPMS
patients,
35
subjects
treated
with
Tcelna showed encouraging results
–
80% of patients showed no disease progression following two years of treatment
–
Substantial reduction in relapse rate following two years of treatment
•
One relapse observed in 21 years of cumulative patient follow up
–
No worsening in physical or psychological condition following two years of treatment
–
Well tolerated, no Serious Adverse Events
•
Strong interest from Key Opinion Leaders, clinical investigators, patients
and potential partners to advance in SPMS
•
Substantial unmet medical need in SPMS
–
Only one product currently approved for SPMS indication with limited use due to cardio toxicity
•
Novel, personalized T-cell approach differentiates Opexa from competition	

	

12
Phase 2b RRMS prior clinical trial
Tcelna showed 37% improvement over placebo (mITT)
(secondary endpoint measurement, primary MRI endpoint measure not met)
n=94
n=48
37%
Total mITT population
n=142
0.214
0.339
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
37% Reduction in Annualized Relapse Rate (ARR)
Tcelna
Placebo	

	

13
Phase 2b RRMS Prior Clinical Trial
Reversal of Disability in Prospective Analysis in More Active Patients
Sub-population of patients (n=50) with more progressed/active disease
profile (baseline ARR >1)
Statistically Significant
Improvement in Disability (p=0.045)
55% Reduction in ARR
Change in Disability (EDSS)
at Week 52
Annualized Relapse Rate (ARR) at week 52
2.4
2.23
2.2
2.39
2.10
2.15
2.20
2.25
2.30
2.35
2.40
2.45
Baseline                             Week 52
Tcelna
Placebo
(p=0.045)
0.28
0.63
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
Tcelna
Placebo
55%	

	

14
Phase I/II SPMS Prior Clinical Trials
Tcelna Stabilizes Disease in SPMS at 2 Years
80%
of
patients
showed
no
further
disease
progression
by
EDSS
at
2
years
Historical Disease
Progression
Tcelna Open Label
(n=35)
*A small percentage of patients in pooled analysis showed an
improvement (i.e. decrease in progression)
**Historical control: ESIMS Study,
published Hommes Lancet 2004
80%
20%
40%
0%
20%
40%
60%
80%
100%
Stabilization vs. Historical Progression
Stable
Progressed	

	

15
Tcelna in Secondary Progressive MS
•
Secondary Progressive MS market
potential in North America could
exceed $7 billion (for all therapies)
•
Roughly 150,000 SPMS patients in
North America
•
Only one drug approved for SPMS in
U.S. (none in EU or Asia)
-
Drug not suitable for chronic use
due to severe side effects
Tcelna being developed to be a
potential therapy of choice in SPMS
SPMS
450,000 Individuals in North America diagnosed with MS;
30-45 % potentially have an SPMS diagnosis
Market Size:
$7 Billion (est.)
Relapsing Remitting MS;
Clinically Isolated Syndrome;
Primary Progressive MS	

	

16
Tcelna
Lead Program Targeting Secondary Progressive MS patients
Fast Track Designation by FDA
•
Phase 2b trial is fully enrolled: 190 patients with SPMS
•
Top line data expected in 2H 2016
•
Design
–
Double-blind, 1:1 randomized, placebo-controlled
–
35 clinical sites in USA and Canada
–
Two annual courses of personalized therapy
–
Efficacy Endpoints: Primary-Whole Brain Atrophy, Secondary-Disease
Progression
•
Immune Monitoring being conducted in parallel
–
Comprehensive biomarker analysis	

	

17
Merck Serono Agreement
Agreement signed 2013; strong potential partner
Option and License Agreement for worldwide rights to all Multiple
Sclerosis indications, excluding Japan
•
If Merck Serono exercises option:
–
Merck Serono to fund any Phase 3, pre-commercial and commercial activities
–
Merck Serono obtains rights to develop Tcelna for all MS indications
–
Worldwide rights excluding Japan
•
Opexa received $5 million upfront option fee at signing
•
Opexa
has
potential
to
receive
additional
$220
million
in
option
exercise and milestone             
payments
•
Opexa has potential to receive royalties ranging from 8% to 15% of annual net sales, with
step-ups occurring if net sales exceed $500 million, $1 B & $2 B
•
Opexa maintains key rights
–
Development and commercialization rights to Tcelna in Japan
–
Certain manufacturing rights
–
Co-development funding option in exchange for increased royalties
–
Rights to all other disease indications	

	

OPX-212:
NEUROMYELITIS OPTICA (NMO)
18	

	

NMO: A Rare Disease with High Unmet Need and 
Significant Market Potential
•
Neuromyelitis optica (NMO) is a rare or orphan autoimmune
disease, affecting the optic nerves and the spinal cord
•
There are no FDA-approved therapies for NMO
•
Any therapy that could achieve tolerization of the AQP-4
reactive T-cells may offer a cure for NMO
•
Opexa retains world wide rights to OPX-212.  Product has
potential to generate $300-$500 million in peak sales, subject
to successful clinical development
•
IND filing expected in Mid 2015
•
Open label Phase I/II clinical trials expected to start in 2H
2015 (subject to IND acceptance and financing)
An orphan disease with no FDA-approved therapy
Image reprinted with permission from MultiView, Inc.
19	

	

20
Recent and Upcoming Expected Milestones
2016
2017
2014
2015
1H
2017 :
Top
line
results
expected from Phase I/II trial
with OPX-212 in NMO (subject
to IND acceptance and financing)
Mid-2015:
File
IND/CTA with US FDA
and/or Canadian health
authorities
2016/17 :
Apply for orphan
and fast track designation for
OPX-212 in NMO
1H 2014:
Complete
enrollment in Phase
IIb SPMS study
2H 2014:
Initiate
second disease
indication: NMO
2H 2015:
Initiate Phase I/II
clinical study with OPX-212 in
NMO (subject to IND
acceptance and financing)
2H
2016 :
Results
from
Immune Monitoring
(biomarker) program
expected
2H
2016 :
Top
Line
results expected in
Phase IIb SPMS trial
20	

	

21
Experienced Management Team and Board of Directors
Neil Warma, President & CEO, Director
›
19+ years international healthcare experience with large Pharma and emerging
biotechnology companies
›
Former Senior Management, Novartis Pharmaceuticals, Basel, Switzerland
›
Former CEO, Viron Therapeutics, Inc.
›
Co-founder and President of MedExact Inc., a company subsequently acquired
Karthik Radhakrishnan, Chief Financial Officer
›
10+ years of health care capital markets experience
›
Formerly, Vice President at ING Investment Management
›
MBA, MS in Engineering, CFA charter holder
Don Healey, Ph.D., Chief Scientific Officer
›
25+ years of experience in cellular immunology and immune regulation
›
Former Director of Immunology, Argos Therapeutics
Donna Rill, Chief Development Officer
›
30 years in cell and gene therapy research and clinical application
›
Designed and validated cGMP Cell & Gene Therapy Laboratories, Vector
Production facilities, and Translational Research Labs
Kenny Frazier, VP of Clinical Dev. and Regulatory
Affairs
›
25+ years of extensive clinical and regulatory experience
›
Formerly, Head of Clinical Operations, Lexicon Pharmaceuticals and Tanox,
Inc.
Board of Directors
Timothy Barabe
Board member of Arqule, Inc.; Former
CFO of Affymetrix, Human Genome
Sciences, Inc., Regent Medical UK and
Sandoz  GmbH
Dr. Hans-Peter Hartung
Chair of Neurology at Heinrich-Heine
University, Germany; Executive Board
member of ECTRIMS
Gail J. Maderis
CEO, BayBio, Former CEO of Five
Prime Therapeutics, Founder of
Genzyme Molecular Oncology
Michael S. Richman
CEO, Amplimmune
Scott B. Seaman
Executive Director,
Alkek Foundation
Neil K. Warma
President & CEO, Opexa	

	

22
SPMS Scientific Advisory Board
Dawn McGuire, M.D., FAAN (Chair)
•
Advisory Council of the Gill Heart Institute
•
Former Vice President of Clinical Research at Elan Pharmaceuticals
Hans-Peter Hartung, M.D
•
Chair of Neurology at Heinrich-Heine University, Düsseldorf
•
Executive Board member of ECTRIMS, World Health Organization Advisory Board on MS
Mark S. Freedman, M.D.
•
Director of the Multiple Sclerosis Research Unit at Ottawa Hospital
•
Multiple Sclerosis Society of Canada, National MS Society (USA)
•
ACTRIMS committee member
Clyde Markowitz, M.D.
•
Director of MS Center at the University of Pennsylvania
Doug Arnold, M.D.
•
James McGill Professor Neurology and Neurosurgery at the Montreal Neurological Institute
Edward Fox, M.D., Ph.D.
•
Director of Multiple Sclerosis Clinic of Central Texas
•
Advisory Committee, Lone Star Chapter of the National Multiple Sclerosis Society	

	

APPENDIX
APPENDIX
23	

	

IMMPATH
:
PROPRIETARY DRUG DEVELOPMENT PLATFORM
24
®	

	

25
Personalized T - cell vaccines
Consisting of Attenuated Antigen Specific T-cell Clones
•
Opexa identifies the exact T-cell
responsible for T-cell-mediated
autoimmune damage, expands the T-cells
in cGMP facility
•
Therapeutic dose of attenuated T-cell
clones is injected subcutaneously
•
Immune system recognizes the large
volume of cells (30-45 million) under the
skin as potential foreign pathogens
•
Attenuated T-cells believed to trigger an
immune response specifically targeting
circulating pathogenic reactive T-cells
Tcelna: lead product candidate in Phase 2b
trial for secondary-progressive multiple
sclerosis
Tcelna
®
Personalized T-cell Vaccine	

	

26
Business Differentiator: Manufacturing Process
Designed for commercialization, Owned and managed by Opexa
Cryopreservation
Formulation/
Irradiation of each
dose as required
Administration: 5
subcutaneous
injections/year
Manufacturing and QC
Dispensation
35 days
Epitope Profiling
1 day
14 days
-
Red Cross
-
Blood Group Alliance
Epitope Profiling
Expansion of antigen specific T-cells
Annual
course
of
treatment
is
5
doses
manufactured
from
a
single
procurement	

	

27
Comprehensive Process to Determine Optimal Additional
Indications Beyond Secondary-Progressive MS
Evaluation Criteria
Short List of
Diseases
Potential Disease
Targets off Platform
First Disease Target
NMO
•
Unmet medical need
•
Competitive landscape
•
Disease incidence
•
Single antigen immunity
•
Multiple antigen immunity
•
Likely duration of Phase 1/2 clinical trial
•
Likely cost of Phase 1/2 clinical trial
•
Clinical endpoint
•
Efficacy biomarker known
•
Animal model available
Addison’s disease
Autoimmune hemolytic anemia
Celiac  Disease
Goodpasture’s syndrome
Grave’s Disease
Hashimoto’s thyroiditis
Idiotypic thrombocytopenic purpura
Myasthenia Gravis
Neuromyelitis Optica (NMO)
Pemphigus vulgaris/foliaceus
Primary Biliary Cirrhosis
Rheumatic heart disease
Systemic lupus erythematosus
Sjögren’s syndrome
Type 1 Diabetes