PHARMAGESIC™TRANSDERMAL SYSTEMAn Innovative Approach to Pain Management

P.O. Box 622, Swiftwater, PA 18370

United StatesTel: +1.570.460.1804

jay@ambianceventures.com

www.pharmadur.com

AmbianceVentures USA

Representing Polytherapeutics, Inc.

PHARMAGESIC OUTLINE

• PharmaDur polymer description.• Performance attributes of PharmaDur in dermal

products.• Pharmagesic™ Transdermal System.

- LOCAL & SYSTEMIC• Intellectual Property• Brief introduction to Polytherapeutics.

PHARMADUR®

POLYMER STRUCTUREWater Soluble Polymer Chain

Water InsolubleStyrenic Polymer Segments

HYDROPHILIC/HYDROPHOBICGRAFT COPOLYMER

COOH COOH

COOH COOH

PHARMADUR“VIRTUAL PATCH”

• Dosage Form: PharmaDur polymer can be formulated into conventional gels, creams and ointments.

• When the formultion is applied to skin, it forms an invisible and imperceptible bioadhesive hydrogel film (“virtual patch”).

• The formed film is retained on skin for 24 hours or until it is washed away.

SCHEMATIC DIAGRAM OF PHARMADUR VIRTUAL PATCH

Kishore Shah, Tracey Vlahovic, and Otto Mills, Poster - New Long Acting Topically Applied Treatments, American Academy of Dermatology Annual Meeting (2007).

B. Michniak-Kohn, K. Shah, B. Kilfoyle, and O. Mills, Poster – Linking Biophysical & Biochemical Findings with Clinical Use, American Academy of Dermatology Annual Meeting (2008).

PharmaDur Film

Stratum Corneum

Epidermis

FLUORESCENCE MICROSCOPIC EXAMINTION OF PHARMADUR FILM ON SKIN

PHARMADUR™ RETENTION ON SKIN

• Fluorescent PharmaDur™ solution in ethanol was painted (X) on hands of a human subject. Examination of the painted surface initially and 24 hours later, under illumination with UV light, showed clearly visible ‘X’.

(AMA Laboratories, New City, NY)

• Assessment by touching site of application with moist finger indicates slippery feel for 24+ hours.

PharmaDur® Dermal Formulations PERFORMANCE ATTRIBUTES

Retains active @ the site of application & provides sustained release of active agent for 24 hours.

Significantly increases the efficacy of penetration enhancer in skin permeation of actives.

Prevents transfer of active to fingers, clothing, towels, and bed linen.

Improves bioavailability & effectiveness of the active.“STRONGER & LONGER”

“PharmaDur® Bioadhesive Delivery System”, K. R. Shah in John J. Wille, ed. “Skin Delivery Systems; Transdermals, Dermatologicals, and Cosmetic Actives”, Blackwell Publishing, Ames, Iowa, © 2006, p 211-222.

KEY ADVANTAGES OF PHARMADUR VIRTUAL PATCH

• Enables delivery of higher dosage of drug or drug having low skin permeability. (Up to 100 to 150 mg /day systemic dose)

• Sustained Therapeutic Effectiveness For 24 hours.

• Flexibility of dosing.• Avoids GI tract. • Bypasses hepatic first pass metabolism.• Ease of manufacture.

PHARMAGESIC™TRANSDERMAL SYSTEM

TWO PRODUCTS1. Provide transdermal delivery of diclofenac

for systemic activity. Produce sustained effective drug concentrations in blood. Once/Day or bid. (SYSTEMIC)

2. Topical delivery of diclofenac for site specific efficacy. (LOCAL)Once/Day

PHARMAGSIC SKIN PERMEATION STUDY

• Solution (50 µl) of the gel placed on surface of human cadaver skin mounted in Franz cell.

• Donor compartment kept open to allow the solution to dry out on skin.

• Receptor phase: phosphate buffer @ pH 7.4 and a temperature of 37° C.

• CONTROL: Voltaren® Gel (Novartis)• Aliquots of the receptor phase analyzed by HPLC

for diclofenac at different time intervals.

DICLOFENAC J FOR SELECTED FORMUALTIONS

Normalized wrt to Voltaren Gel = 1.16 mcg/sq. cm. hr

0

2

4

6

8

10

12

14

16

18

1 2 3 4 5 6 7 8 9

Formulation Number

Dic

lofe

nac

J, m

cg/s

q cm

. hr

DICLOFENAC J, mcg/sq. cm. hrSubject to Subject Variations

Cadaver Donor Number

Voltaren Gel Pharmagesic SYSTEMICNormalized wrt Voltaren Gel

1 0.62 1.23 1.6 10.54 0.4  5 0.5  6 2 97 1.3 12.58 1.2 10.79 0.5 16.7

10 2.3 12.4

AVERAGE 1.16 12

DICLOFENAC, J

-500

50100150

200250300

350400

0 5 10 15 20 25 30 35

Time, hours

Cum

ulat

ive

Am

t of D

iclo

fena

c,

mcg

/sq.

cm Pharmagesic SYSTEMIC

Voltaren Gel

B. Michniak-Kohn , D. Kaushik, and K. Shah, unpublished results (2010)

PHARMAGESIC™ LOCALPRODUCT DESCRIPTION

Dosage Form: Medium viscosity clear hydroalcoholic gel/solution.

API: Diclofenac sodium.Ingredients: USP and/or FDA approved

pharmaceutical excipients &PharmaDur® polymer.

Application: ~ 700 mg Gel Once/day over affected area (e.g. knee, wrist, tendon, etc.).

When applied to skin, it dries to form an invisible PharmaDur® hydrogel film (Virtual Patch) containing the drug and the excipients.

PHARMAGESIC LOCALVS VOLTAREN GEL

PerformanceProperty

Voltaren® Gel Pharmagesic LOCAL

Efficacy Effective J = ~ 3 x Voltaren Gel

Dosage 2-4 grams/knee 700 mg/knee

Dosing Frequency

4 times/day Once/day

Drying Time ~ 10 minutes ~ 5-7 minutes

PHARMAGESICINTELLECTUAL PROPERTY

• U.S. Patent 5,942,243Mucoadhesive compositions for administration of biologically active agents to animal tissue.

• EP 1 077 678 B1Mucoadhesive compositions for administration of biologically active agents to animal tissue.

• Composition for transdermal administration of non-steroidal anti-inflammatory agent - U.S. Patent Pending.- PCT International Pending.

PHARMAGESIC SUMMARY• Pharmagesic LOCAL offers significant

performance enhancement over competitive products (Voltaren & Pennsaid).Greater effectiveness with once/day dosing vs 4 times /day dosing

• Less product application per dose.~ 700 mg per dose Vs 2 or 4 g per dose

• Internationally patent protected technology.• Available marketing exclusivity.

THE PHARMADUR EFFECT• PharmaDur polymer exerts a profound effect on

enhancement of the penetration rate of a drug through skin. Skin permeation enhancer by itself is not the sole determining factor. e.g Diclofenac JPharmagesic SYSTEMIC / JPennsaid = ~ 50NOTE: Pennsaid® Solution contains 45% DMSO, a powerful skin penetration enhancer.

• Combination of the Virtual Patch & the rate enhancement effect enables transdermal drug delivery dosages up to 100-150 mg of /day.

SCOPE OF TRANSDERMAL DRUG DELIVERY

ALL DRUGS

Currently Feasible for Transdermal Delivery

Feasible with PharmaDur® Virtual Patch Technology

POLYTHERAPEUTICSMISSION

• Research & DevelopmentPolymer Technologies & Products for Pharmaceutical & other Healthcare Uses

• License Products to other Corporations for World Wide Marketing

• Manufacture PTI Developed Products for Corporate Licensees where applicable.

POLYTHERAPEUTICS, INC.• Research & Development laboratory in New

Brunswick Technology Center, New Brunswick, NJ.• PharmaDur™ delivery system is commercially

utilized in two Rx dermatological products and more than 15 cosmetic products by licensees of Polytherapeutics. (e.g. Umecta® PD & Aclaro® PD, JSJ Pharmaceuticals; High Definition Healthy FX Foundation, Smashbox Cosmetics – Estee Lauder, Murad Cosmetics)

• Collaboration with a big pharma company in ophthalmic drug delivery.

www.pharmadur.com

PharmaGesic™

Performance

EnhancementProduct

Differentiation

MarketingEdge

AmbianceVentures USA – Global Marketing PartnersJay@Ambiance-Ventures.com

Global licensing opportunity