Neurocarrus - Nonaddictive pain treatment

Treating Pain Without Addiction Using Targeted, Non-Opioid Pain Therapeutics

1. Targeted, Non-Opioid
Pain Therapeutics
Treating Pain
Without Addiction
For more information:
[email protected]

2. 2
Current drugs for severe pain are addictive and toxic resulting in
hundreds of thousands of deaths per year
Neurocarrusdeveloped N-001 for treatment of
severe pain without addiction or off-target effects
N-001 is a first-in-class long acting anesthetic-like
drug. Its unusual duration could reduce or avoid
opioid use.

3. 3
~90M Pain
Patients a
year
~50M Acute
Pain Patients
a Year
~500K
Patients at
entry (1%
of market)
At a price point of $500 per dose
(conservative estimate based on
anesthesia price) this is market entry at
$250M revenue which could quickly grow
100 fold.
The Company estimates a net profit of
$200 per doseaccomodatingscale up
manufacturing and cGMP production
costs.
Domestic Market Analysis
N-001 is poised to reach a massive market
Disclaimer: future revenue projections are not
guaranteed.

4. 4
Traction
N-001 has success in funding, partnerships,
and preclinical testing
•Highly competitive
accelerator $250K
equity funding
•Crowdfunding
current and past
$350K equity
funding
•$300K non-dilutive
grant awards
Preclinical Trial Metrics*
Longer acting
than current
anesthesia
Eliminates
pain like
behavior
*Independently confirmed by CRO and Stanford
University using double blinded procedures
Visual proof
of specific
targeting
•Over $3M in n on-
dilutive SBIR grant awards
•Conducting
independent
testing

5. 5
•Patent No. 10,633,643 “Engineered
Clostridium botulinum toxin adapted to
deliver molecules into selected cells” issued
by the USPTO on April 28, 2020
•Follow on divisional Patent No. 11,118,170
issued May 19, 2021
•Neurocarrus
exclusively licensed these
patents for all- fields-of-use along with a
sublicense option.
•PCT US 1632573 has issued in Japan 2017-
559588(6-17-21) and EU and is pending in
Canada, Israel, and South Korea.
•
Two New Patent Filings 2024 –extending IP
sales protection to 2044
Intellectual Property

6. 6
Allen et al 2023 Sci Rep
PMID: 37479740
Allen et al 2020 Sci Rep 10,
12789 PMID: 32732905
Pavlik et al 2017 Current
Topics in Peptide and
Protein Research 2017
18:1-15
Pavlik et al 2016 Nature Sci
Reports 6:23707 PMID:
27025362
Publications




Repurposed bacterial toxins for human therapeutics
Benjamin J. Pavlik
1
, Kevin E. Van Cott
1
and Paul H. Blum
2

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

7. 7
Pre-clinical
Research
IND
Clinical Trials
N-001 Development Timeline
Invention &
Founding Patents
Out-licensing income
New Patents
Phase IPhase II Phase III
20252026 2027 2028 Protected Sales
2028 -2044
Investor Exits by
Corporate Acquisition
IND Phase II Phase III
Valuation Cap
(Michaeli 2022; Truebel 2020)
$11.25M $100M $1B $4B
Drug
Approval
Timeline

8. 8
Paul Blum, Ph.D.
Founder and CEO.
Serial inventor and
entrepreneur.
Team
Derek Allen, Ph.D., Research Scientist. N-001
manufacturing and
mechanistic expert
Board
JianguoCheng, M.D.,Ph.D.
Professor of Anesthesiology
Cleveland Clinic, Former
President ofAmerican
Academy of PainMedicine
Mark Blum, JD
Attorney licensed in California.
U. California College of the Law, San
Francisco –Contract Law
Vicky Valverde- Salas, MD
Primary Care Clinic
Director and chronic pain
treatment..
Bruce McDonald, JD
Partner in the intellectual property
group at Smith, Gambrell &
Russell, LLP. USPTO adviser