Treating Pain Without Addiction. Neurocarrus invented a new way to control pain. We created a novel protein with multiple functions that targets pain neurons, enters them and delivers a therapeutic payload that shuts down pain signalling. The drug, N-001, is administered peripherally where the pain occurs. It is long acting and not addictive. It does not enter the brain. We are in preclinical development and want to start clinical trials as soon as possible. Neurocarrus is actively raising funds to achieve these goals.

1. Targeted, Non-Opioid
Pain Therapeutics
Treating Pain
Without Addiction

2. 2
2018: The opioid epidemic rages on…

3. 34

4. 4
BOTOX freezes motor neurons…
…what if we could freeze pain
neurons?
With N-001, we can.

5. 5
N-001 Profile
• A rationally designed protein
that targets pain (sensory)
neurons and active only inside
them
• Disrupts pain signaling by
neuronal axon through
modification of cytoskeletal
actin that alters ion channels
• Locally administered at site of
pain by injection or topical
application
• Uses our novel drug delivery
system, capable of transporting
other drugs to targeted neurons
Video Link

6. 6
N-001 eliminates acute pain.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
UNTREATED N-001 (20%) OPIATE
PainRelief
Treatment and Dose
N-001 Vs. Opioid In Formalin Pain Test (Mouse)
n=7 n=20
Relief from exposure
to inflammatory pain
equals that of
opiates. Movement
remains normal.

7. 7
N-001 decreases acute pain
for longer than opiates.
0%
20%
40%
60%
80%
100%
PainRelief
Days after treatment
1 2 5 7

8. 8
N-001 eliminates chronic pain.
N-001 Chronic Pain Test (Mouse), Carageenan Sensitized
I
Females treated
with N-001
PainRelief
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Untreated Males treated with
N-001
I I
Chronic pain created by
carrageenan sensitization
increases inflammatory
pain by 55%. N-001
specifically eliminates
this.

9. 9
Global Pain Treatment Market (Pharmaceutical):
$32 billion
Annual U.S Patient Population
Post operative pain : 50 million (acute)
Shingles : 1.3 million (chronic)
Diabetic Neuropathy : 15 million (chronic)
Osteoarthritis : 30 million (chronic)

10. 10
Exclusive license
for all fields of use
(drug and delivery
system)
PCT filed in 8
countries
Intellectual
Property

11. 11
Nature
Current Topics in
Peptide and Protein
Research
Publications
Repurposed bacterial toxins for human therapeutics
Benjamin J. Pavlik1
, Kevin E. Van Cott1
and Paul H. Blum2
1
Department of Chemical and Biomolecular Engineering, 207 Othmer Hall,
University of Nebraska-Lincoln, Lincoln, NE 68588-0643; 2
School of Biological Sciences,
1901 Vine Street, University of Nebraska-Lincoln, Lincoln, NE 68588-0665, USA.
ABSTRACT
Pathogenic bacterial toxins can be repurposed
as therapeutics. Binary bacterial toxins are
macromolecular complexes that are a current focus
of therapeutic development. These proteins bind
to surfaces of specific human cell populations and
transport enzymes across membranes. Basic research
has characterized bacterial toxin mechanisms and
structure so that protein domains can be “shuffled”
for a variety of applications. This approach delivers
an already characterized enzyme to new cell types,
specified by binding affinity. Separated protein
components from holotoxins are also repurposed
into drug delivery applications to form composite
multifunctional drug delivery units. Enzymatic
domains are used for cancer diagnosis and treatment,
influence of intracellular trafficking, and for providing
relief from pain, autonomic disorders, movement
disorders, spasticity, and HIV. Technical challenges
to this field are the immunogenicity, solubility and
stability of therapeutic fusion proteins. Clinical
intervention and predictive computational approaches
identify, prevent, and remove known and predicted
immunogenicity without a significant loss of
efficacy. Unrealized medical potential exists in a
wealth of bacterial diversity that may be captured
by the repurposing of bacterial toxins.
KEYWORDS: bacterial AB exotoxins, protein
engineering, human therapeutics, biologics, drug
delivery
INTRODUCTION
Therapeutic repurposed bacterial toxins (repTox)
are derived from naturally occurring proteins that
target, enter, and disrupt the biological structures and
processes of cells. Many repTox are sophisticated
membrane-associated proteins with high aqueous
solubility, capable of targeted molecular transport to
specific human cell types and intracellular locations.
Treatments for cancer and neurological disorders
have been the focus of several clinical trials [1-4],
but only two have been approved for therapeutic use.
Clostridium botulinum neurotoxin serotypes A and
B (Botox®
, Dysport®
, Xeomin®
, Myobloc®
) can be
purified directly from the microorganism and are
locally administered cosmetics and therapeutics
that cause neuromuscular paralysis. Engineered
interleukin-2-diphtheria toxin (Ontak®
) is an
intravenously injected cancer therapeutic produced
by recombinant biotechnology that combines the
biomolecular functions of interleukin-2 and diphtheria
toxin from Corynebacterium diphtheria to target
IL-2 receptors on the cancer cell surface and gain
entry into the cytoplasm to disrupt a vital protein
translation factor. The potential of these functionally
efficient bacterial components has not yet been
fully realized in the context of human health, and
may provide many new treatments and biomedical
research tools [5-13]. Development of repTox into
therapeutics has been enabled by advances in
protein engineering and functional proteomics. This
minireview considers current human therapeutic
applications of repurposed bacterial toxins using
protein engineering and biotechnology.
Structure/function of bacterial toxins
Pathogenic bacteria have evolved to produce a
swarm of proteins (Table 1), lipopolysaccharides
and effectors to increase virulence [14, 15], but
Current Topics in
Peptide & Protein
R e s e a r c h

12. 12
Paul Blum, Ph.D. CEO
University of Nebraska – Lincoln
25 years of protein development
U. Nebraska Inventor of the Year 2015
Marina Blum Operations
University of California - Berkeley
BA – Public Health
Team
Jianguo Cheng, M.D., Ph.D.
Professor of Anesthesiology
Cleveland Clinic, President Elect
American Academy of Pain Medicine
Richard L. Stieg, M.D., MHS
Former President of American Academy of Pain
Medicine
Founding Member, National Pain Foundation
Stephan B. Abramson, Ph.D.
LifeSci Partners, LLC.
Formerly Director of Clinical
Affairs, Alpha Therapeutic Corp.
Board
Partners

13. 13
The Future of
N-001 Pain Treatment

14. For more information
please reach out to:
paul@neurocarrus.com