The document summarizes presentations from a symposium on medical technologies in North Carolina. It discusses technologies for combat casualty care, nitric oxide therapies for wound healing, and topical applications of nitric oxide. It also profiles companies developing nitric oxide wound treatments and cyanoacrylate surgical adhesives, and introduces a new diagnostic test for protease activity in wound fluid.

1. North Carolina Federal Advanced Technologies Symposium
May 9, 2013
Medical Technologies Forum
Hosted by:
Office of Senator Richard Burr
NC Military Business Center
NC Military Foundation
Institute for Defense & Business
University of North Carolina System
Reception Sponsor:
Bronze Sponsor:

2. CONFIDENTIAL

3. CONFIDENTIAL
Corey Russ
May 9th 2013
Combat Medical Systems
NC Advance Technology Symposium

5. Phases of
Tactical Care
• Care Under Fire
• Tactical Field Care
• Tactical Evacuation

6. Early Lessons
• Standardize techniques
• Simple devices
• Command responsibility
• Train-as-you-fight

7. THANK YOU
Combat Medical Systems
5845-D Yadkin Road
Fayetteville, NC 28303
910.426.0003
www.combatmedicalsystems.com

8. • Exclusively devoted to developing nitric oxide-based
therapies
• Founded by Drs. Mark Schoenfisch and Nathan Stasko
• Core platform technology licensed from the University of
North Carolina at Chapel Hill
• Began operations in 2008
• Raised ~$20M in equity financing from high-net-worth
individuals
• Awarded ~$7.5M in federal contracts and grants from DOD,
NIH and NSF
Novan, Inc.

9. Why Nitric Oxide?
Your body is making nitric oxide every second of every day.
Nitric oxide plays an important role in:
• Wound healing
• Blood pressure control
• Immune function
Nitric oxide has antimicrobial activity:
• Targets gram positive and gram negative bacteria, fungi, and
viruses
• Disrupts mature biofilms and kills bacteria embedded in
biofilms
• Non-antibiotic strategy; no known mechanisms of drug
resistance
Nitric oxide is a gas which is difficult to store and deliver

10. BURN INJURIES DIABETIC FOOT ULCERS
~4 million in the US per year
Cost of ~$8,000 per episode
“Someone, somewhere, loses a leg
because of diabetes every 30 seconds
of every day.” (Lancet, 2005)
$35.6B cost to US
healthcare system
~2.4 million burn injuries per
year in the U.S.
650,000 are treated by medical
professionals
2/3 of patients experiencing
more than 40% TBSA die as a
result of sepsis or other
complications.

11. Department of Defense, US Army
• Topical Nitric Oxide for the Treatment of Acute Military Wound Infections (SBIR
Phases I/II and Option - 2011-2014)
• Effects of Topical Nitric Oxide Formulations on Sulfur Mustard and Thermal Burn
Injuries (Cooperative Research & Development Agreement - 2010)
• Evaluation of Antimicrobial Wound Dressings on Infected and Non-infected
Wounds in a Swine (sus scrofa) model, Amendment 5 (Cooperative Research &
Development Agreement - 2013)
National Institutes of Health
• Nitric Oxide-Releasing Wound Dressing for Treating Chronic Wound Infections
(SBIR Phases I/II – 2008-2013)
• Use of a Nitric Oxide-Loaded Gel to Improve Healing Outcomes of Burn Injuries
(SBIR Phase I – 2012-2013)
Novan Topical Nitric Oxide
Wound Care Contracts and Grants

12. Novan Topical Nitric Oxide
Current Status
• Clinical trial materials (drug substance and drug product) are
manufactured and packaged at Novan’s facilities under GMP.
Drug Substance Drug Product
• Intellectual property portfolio includes >50 patents and
applications with worldwide coverage and 15-20 years of patent
life.
• IND for a topical wound care ointment to be submitted in 2013 to
support future clinical studies.

13. - CONFIDENTIAL - ©2011 Adhezion Biomedical, LLC. All Rights Reserved.
OVERVIEW OF ADHEZION BIOMEDICAL
Page  13
ADHEZION BIOMEDICAL BRINGS INNOVATION TO CYANOACRYLATE-BASED MEDICAL DEVICES
Adhezion Biomedical, LLC is a privately held medical device
company focused on the development, manufacturing and
commercialization of highly differentiated and proprietary
cyanoacrylate-based surgical, wound management and
infection prevention products.
Surgical Solutions
Improve clinical
outcomes in the surgical
specialties with an
emphasis on the O.R.
and E.R. settings.
Infection Prevention
Reduce or eliminate the
incidence of Healthcare
Associated Infections
(HCAIs).

14. - CONFIDENTIAL - ©2011 Adhezion Biomedical, LLC. All Rights Reserved.14
WHAT IS CYANOACRYLATE?
Page  14
• Today’s commercially available cyanoacrylate tissue adhesives can be segmented into two distinct product categories
based on the product’s chemical structure.
Practical comparison of 2-octyl cyanoacrylate (OCA) and n-butyl cyanoacrylate (BCA) Formulations
Property OCA
(SURGISEAL, Dermabond, Derma+Flex QS)
BCA
(Histoacryl, Indermil, LiquiBand, GluStitch)
Chemical Composition
Film Flexibility Higher Moderate
Wound-Breaking Strength1,2 Stronger Strong
Heat released Less More
Setting time Short (minimizes clogging) Shorter
Water Resistance Patient may shower immediately Patient may not shower for 24-48 hours3
Incision Length
Clinically proven to close long
incisions4
Clinically proven to close up to 4-5 cm3,5
Microbial Protection Coverage
Area
Greater Moderate
BO
8-carbon side chain 4-carbon side chain
[1] Perry LC. An evaluation of acute incisional strength with traumaseal surgical tissue adhesive wound closure. Findings by: Dimensional Analysis Systems, Inc., Leonia, NJ. 1995.
[2] Singer AJ, et al. Comparison of wound-bursting strengths and surface characteristics of FDA-approved tissue adhesive for skin closure. J Adhes Sci Technol. 2004;18:19-27.
[3] HISTOACRYL [package insert]. B. Braun; 2009.
[4] Blondeel P, et al. Closure of long surgical incisions with a new formulation of 2-octylcyanoacrylate tissue adhesive vs. commercially available methods. Am J Surg. 2005; 188:307-13.
[5] INDERMIL [package insert]. Norwalk, CT: United States Surgical/Syneture; 2002.

15. - CONFIDENTIAL - ©2011 Adhezion Biomedical, LLC. All Rights Reserved.Page  15
WOUND CLOSURE OVERVIEW
Wound Closure Options
Sutures
• Traditional method
• Easy, safe, cheap
• All internal layers are
normally sutured
• Large incisions
• Deep layers
• Delicate areas (eyes, lips,
etc)
• 95% of incisions are still
sutured
Staples
• Large wounds in areas
requiring extra holding
strength
• Speed is main advantage
• Cosmesis is okay
• Painful to remove staples
• Staple removal is an extra
procedure/cost
Adhesive Strips
• For small wounds only
• No tension
• Poor holding strength
• Not waterproof
• Limited applications
Liquid Adhesive
• No needles
• Reduced anxiety
• Quick closure
• Secure closure
• No removal of sutures or
staples
• No dressings required
• Waterproof closure
• Cost advantage
• Wide applications
SURGISEAL® TOPICAL SKIN ADHESIVE: MARKET ASSESSMENT

16. - CONFIDENTIAL - ©2011 Adhezion Biomedical, LLC. All Rights Reserved.
SURGISEAL® TOPICAL SKIN ADHESIVE: KEY ATTRIBUTES
Page  16
TEARDROP APPLICATOR
2-octyl
cyanoacrylate
Formula contains
embedded activator
(consistent ratio)
No glass in applicator
Sponge can be utilized
with broad or narrow
strokes
Apply 2 layers
Lasts 5-7 days
on skin

17. - CONFIDENTIAL - ©2011 Adhezion Biomedical, LLC. All Rights Reserved.
SURGISEAL® TOPICAL SKIN ADHESIVE: KEY ATTRIBUTES
Page  17
APPLICATION INSTRUCTIONS

18. One Step Wound TestTM

19. Protease Activity in Normally- and Non- Healing Wounds

20. One Step Wound TestTM
Before (left) and After
Reaction With Protease

22. The One Step Wound TestTM
is:
1. Non-invasive—using a drop of Wound fluid
as a diagnostic fluid;
2. Inexpensive--less than $0.05 CGS;
3. Rapid--< 10 min in total;
4. One step--a passive separation;
5. Colorimetric--red-to-grey color change;
6. Sensitive--detection limit approaching ~15
nanogram of a model protease;
7. Selective--only gelatinase activity is
detected;
8. Instrumental Readout--using an inexpensive
$200 turbidimeter;
9. Easy to use-- No training needed;
10. Room Temperature—where the reaction
takes place; it’s stable at room temperature.
11. Quantitative--kinetic analysis provides
nanogram resolution for an improvement over
a yes/no result