Applied Catheter Technologies is a medical device company focused on maximizing the performance of existing medical devices and the effectiveness of surgical procedures, with the addition of Halofuginone, which acts to limit or eliminate, scar tissue formation. Halofuginone is a potent, non-toxic type 1 collagen synthase (and to a lesser extent type 3) inhibitor. It’s effect is blocking the trophic effects of TGF-β on collagen synthase.

1. Executive Summary
October 2013
Paul Rohricht MS MBA
Scott Washburn MD

2. “ A p p l i e d C a t h e t e r T e c h nol og i e s i s a m e d i c a l d e v i c e c o m p a n y f o c us e d o n m a x i m i z i ng
t h e p e r f or m a n c e o f e x i s t i ng m e d i c a l d e v i c e s a n d t h e e f f e c t i v e n e s s o f s u r g i c a l
p r o c e du r e s , w i t h t h e a d d i t i on o f H a l o f u gi no ne , w h i c h a r e i n h e r e n t ly l i m i t e d b y s c a r
t i s s ue f o r m a t io n. ”

3. History
Formed in 2008 to develop a series of products which combines existing
medical devices with specific collagen-inhibiting pharmaceuticals, in order to
greatly enhance the performance of the devices.
Research conducted by Dr. Steve Hodges of Wake Forest University and the
Institute for Regenerative Medicine discovered a potent Type I collagen
inhibitor, halofuginone, that prevented excessive collagen deposition and
thereby eliminates the formation of a stricture (scar tissue).
Excessive collagen deposition is the root cause of scar tissue, resulting in
strictures and adhesions throughout the human body. Collagen deposition
occurs whenever the body suffers an injury due to trauma or surgical
procedures.
ACT has secured exclusive rights to the patent estate from Wake Forest
University and is developing a suite of products which addresses high unmet
clinical need that focus on the anti-scarring properties of halofuginone.

4. Halofuginone
Halofuginone is a potent, non-toxic type 1 collagen
synthase (and to a lesser extent type 3) inhibitor. It’s effect
is blocking the trophic effects of TGF-β on collagen
synthase. Halofuginone is an ancient Chinese herbal
remedy derived from the roots of a species of Hydrangea.

5. Procedures at Risk
Urological Procedures*
Abdominal Surgeries
Plastic Surgery/Aesthetic
Benign Esophageal Strictures
Benign Biliary and Pancreatic Strictures
Benign Bowel Strictures
Tendon and Ligament Surgery
Veterinary Surgeries
*Initial clinical target.
Excessive collagen
deposition is the root
cause of scar tissue,
resulting in strictures
and adhesions
throughout the human
body.
Collagen deposition
occurs whenever the
body suffers an injury
due to trauma or
surgical procedures.

6. The Basic Problem
Early intervention is critical!
Normal wound healing begins when inflammatory and
coagulation cascades initiate a series of events resulting in a
“clot cover” of the injury site, which is mainly composed of
thrombin and fibrin. The injured tissue heals beneath this
cover.
When healing is complete, plasmin breaks down fibrin and
exposes the healed, healthy tissue. If the balance between
the formation and the destruction of fibrin is correct, then
adhesion formation after tissue injury/damage should not
occur. Whenever there is an inadequate breakdown of the
fibrin matrix (fibrinolysis), there is an ingrowth of
fibroblasts, blood capillaries, and nerves that lead to the
formation of permanent fibrous connective tissue, or
adhesions and strictures.
Adhesions are primarily composed of Type 1 collagen,
whose formation is driven by the substance TGF-β. The
progressive accumulation of collagen connective tissue and
accompanying capillaries and nerves can destroy normal
tissue architecture and disrupt its normal function as seen
with urethral strictures, exuberant granulation tissue, keloid
scarring, and atherofibrotic joint contracture, and implant
encapsulation, among others. The healing process is
depicted in Figure 1. The phase of scar formation (fibroplasia
phase) begins within 24 hours of injury and under normal
circumstances, resolves by the 14th day after injury.
Adhesion and stricture formation represent a prolongation
of the proliferatve phase of healing.

7. Initial Proof of Concept
Rabbit study using a halofuginone
food supplement (oral). Egypt
Normal diet
Rat study using a halofuginone
coated silicone catheter. Wake
Forest
Normal Rat
Scar
Halofuginone diet
Non-coated catheter
Inflammation
Coated catheter
Additional studies have been performed at Wake Forest using halofuginone coated devices
in the esophagus, trachea and abdomen with comparable results.

8. Our Solution
 Candidate Drug: Halofuginone; Type I collagen inhibitor with
exceptional potency and low toxicity.
 Pre-clinical research: In rabbit and rat with excellent scar prevention in
urethra, ureter, esophagus, trachea and abdomen.
 Catheter: Supplied by Degania Silicone, Israel, FDA 510(k) approved.
 Halofuginone: cGMP Synthesis by Scynexis, Durham NC.
 Coating Process: Proprietary process in conjunction with Covalon
Technologies, Toronto, Canada.
 Regulatory Processes: Regulatory submissions, ISO and Design
Controls conducted by ACT.

9. HaloGel and Abdominal Adhesions:
Rat Cecal Abrasion Model
A
Extent of Adhesions
*
**
*
B
Tenacity of Adhesions
*
*
Figure 1: Scatter plot of adhesion extent and tenacity. (A) Significantly less adhesions were present in the
keratin-halofuginone treated animals than other groups. (B) Keratin-halofuginone group showed
significantly less dense adhesions than Interceed and keratin alone. * - p < 0.05, ** - p < 0.01, (KH)
keratin-halofuginon hydrogel.
Peyton, et al J Surg Research, 2012

10. Development Milestones
Phase 1
Phase II
Phase III
Design Control and Regulatory Documentation
Patent
Filings
Additional Patent Filings and Prosecution
Prototype
Development
Prototype
Validation
Coating
Development
Coating
Validation
Halofuginone
Synthesis (RG)
Halofuginone
cGMP Grade
Pre-Clinical
Testing
Cytotoxicity
Testing
1st Human Trial
Orphan Status
Urethral Strictures
Prevention
2nd Human Trial
Orphan Status
Urethral Strictures
Treatment
FDA
Submissions
510(k)

11. Medical Directors
Anthony Atala, MD
Urologist
Steve Hodges, MD
Urologist
Christopher Sullivan, MD
ENT
Vincent D’Souza, MD
Radiologist
T.J. Pulliam, MD
Gastroenterologist
Scott Washburn, MD
OB/GYN

12. Partners
covalon

13. World Market Urological Catheters
Urethral Catheters
Ureteral Stents
2012
$900 MM
$100 MM
$ 1.13 B
US
50%
Europe
35%
Japan
10%
ROW
5%

14. Additional Markets
Abdominal Adhesion Barriers
$600 MM (2013)
Plastic Surgery/Aesthetic
$2.8 B
Benign Esophageal Strictures
$40 MM (Est.)
Biliary and Pancreatic Stents
$76 MM (2010)
Gastrointestinal Stents (bowel)
$22 MM (2010)
Tendon and Ligament Surgery
$50 MM (Est.)
Equine (below the hock) injuries
$50 MM (Est.)
(2010)
$3.6 Billion
1

15. Business Model
• Develop a suite of medical devices specific to a particular
disease area;
• Add value by demonstrating safety and efficacy in human
clinical trials;
• License those devices to key players;
• Longer-term: exit via acquisition of ACT

16. Partnering
Market
Size
License Fee
Urological Devices
$1 BB+
$40-$50 MM
7%
Abdominal Adhesion Barriers
$500 MM $20-$30 MM
7%
Plastic Surgery/Aesthetic
$2.8 B
$50-$75 MM
7%
Esophageal Stents
$40 MM
$10-$15 MM
7%
Biliary & Pancreatic Stents
$76 MM
$25 MM
7%
Gastrointestinal Stents (bowel) $22 MM
$5 MM
7%
Tendon and Ligament Surgery $50 MM
$20 MM
7%
Equine (Below the Hock)
$20 MM
7%
$50 MM
$190-$240 MM
Royalty
$20-$40 MM Ann. Est.

17. Thank You
Contact:
Paul Rohricht MS MBA
prohricht@appliedcatheter.com
(704) 249.8342