Tissue Patch 3 Information For Distributors V1

Information for Distributors

Background to Tissuemed •

Tissuemed is a prominent medical device company based in Leeds, UK

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Founded by surgeons as a University spin-out (mid-1970’s)

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Initially focused on tissue heart valves and grafts

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Current R&D focus is on: – Tissue Sealants / Contact Adhesives / Local Delivery

A few definitions of words you will see: Haemostasis: Literally “static (still) blood”….slowing blood flow down will result in it clotting (flow rate?). Haemostat….something that stops blood flow. Thrombogenic: Literally “clot-generating”…..so a thrombogenic haemostat works by biochemically inducing a clotting reaction. Thrombogenic materials are typically proteinaceous (collagen/fibrin). Importantly Tissuepatch3 is NOT a thrombogenic haemostat…..it only induces clotting by virtue of its barrier effect which slows blood flow to levels at which it will clot, which is why it is only indicated for mild to moderate bleeds.

Covalent: Interaction between molecules resulting in a strong physical bond. Electrostatic: Lower level bonding between atoms carrying opposite charges. Autologous: Derived or transferred from the same individual’s body Multilaminate: Many layered

The Product –Tissuepatch3

What is Tissuepatch3 ? ⇒Tissuepatch3 is a sealant and barrier film for the adjunctive prevention of air, blood and/or fluid leakage in thoracic and general surgery ⇒Tissuepatch3 is a completely synthetic product. Unlike commonly used sealants and haemostats it does not contain any human or animal derived materials.

What isn’t Tissuepatch3 ? ⇒Tissuepatch3 is not a thrombogenic haemostat. It is not designed to biologically induce clotting and therefore will not stop significant bleeds.

Tissuepatch3 Description • Thin film (≤40µm), flexible, integrated tissue sealant, barrier and adhesive • Made from absorbable synthetic materials • Highly versatile • Self-adhesive and tissue-bonding • Dry and ready-to-use Barrier laminate Sealant laminate overprinted with brand Cohesive laminate Sealant and Adhesive laminate

Cross section: Adhesive, sealant and barrier properties provided by fused laminate structure preformed in manufacture

Product Advantages ⇒ Cost-Effective:

Reduced OR time, tissue support during wound healing, and reduced hospital stay.

⇒ Broad Sealing:

Self-adhesive patch that forms a blood/fluid/air tight seal

⇒ Strong:

Strong adhesion with cross linking in situ.

⇒ Flexible/Elastic: Can be applied to non-uniform surfaces. ⇒ Easy to Use:

“Open and Apply”. No guns, no cartridges, no preparation required, Bonds to surgical site in <30 seconds.

⇒ Synthetic:

Constructed from synthetic polymers. No human or animal material. Gamma-sterilized. Absorption in about 50 days.

⇒ Approvals:

CE mark approved

Indication Tissuepatch3 is indicated for use to seal and reinforce against: ⇒ air leakage in thoracic surgery, e.g. lung resection ⇒ leakage of low pressure or oozing bleeding in general surgery Tissuepatch3 is intended for use as an adjunct in thoracic and general surgery. It is not intended to replace sutures or staples. When bleeding or air leak cannot be controlled with conventional methods, Tissuepatch3 can be applied to a wound to seal the area effectively within 30 seconds.

Mechanism of action Tissuemed’s patented polymer technology enables Tissuepatch3 to bond to a range of tissue surfaces in a two-stage process.

Preclinical efficacy The preclinical efficacy of Tissuepatch3 has been demonstrated using two surgical models: • Thoracic • General Both show Tissuepatch3 to be an effective treatment for the sealing of air and blood leaks.

Thoracic surgery model • • • •

Porcine lung (n=6) Punch biopsy to create pleural defect Acute air leak grading 14 and 28 day recovery

Thoracic surgery model

t ≤ 30 minutes

t =14 days

General surgery model • • • •

Rabbit liver (n=9) Punch biopsy to create low rate bleed Acute blood loss collection 1, 2 and 4 month recovery

General surgery model

t < 10 minutes

t = 2 months

Clinical performance History Tissuepatch3 is based on the clinically proven benefits of Tissuepatch2, while offering improved flexibility and conformance to tissue. Tissuepatch2, has been used clinically by thoracic surgeons. This product, using Tissuemed’s adhesive polymer as a dry powder has been shown to be effective in reducing air leaks.

Clinical performance – Tissuepatch2 Multi-Centre Clinical Investigation to Evaluate the Safety and Performance of Tissuepatch2 in the Prevention of Air Leaks Following Lung Resection • Target population: Patients undergoing lung resection • Two centre study with 3 Clinical Investigators • Patient treatment completed - 17 • Follow-up - 6 weeks, 3 and 6 months

Clinical performance – Tissuepatch2 • Easy to handle and apply

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• Immediate and sustained reduction in air leaks

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• Normal fluid discharge and patient recovery

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• Early removal of chest drain(s) (107 hrs v 125-166 hrs)

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• Early hospital patient discharge (6 days v 10-14 days)

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• No device related adverse events

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• Strong surgeon endorsement Tiss uemed Op in io n: Tiss uep atch 2 has p ro ven ef ficacy and safety . Tiss uep atch 3 is e xp ected to maxi mise al read y ver y sub stant ial comp etitive a dvantag es

Clinical performance – Tissuepatch2 • Tissuepatch2 performs better than Tachosil (Nycomed). • Tissuepatch3 is expected to offer further improvements

Clinical performance – Tissuepatch3 A Post-Market Surveillance Study of the Safety and Performance of Tissuepatch3 in the Prevention of Air Leaks Following Lung Surgery • Target population: Patients undergoing lung surgery • Two centre study with 2 Clinical Investigators • Patients to be treated - 20 • Follow-up - 6 weeks and 3 months Comments to Date: “Extremely Good First Impressions”

Matrix of competitive sealant products used in Lung Surgery Company

Product

Product Type

Selling price*

Source/Material

Preparation/ Application time

Efficacy (Reason)

Comments

Baxter

Tisseel

Liquid

£200

Human/Animal

Preparation Time – 15-20 mins*** Application Time – 1-2 mins

Low(Strength)

Haemostat action greater than sealant effect

CSL Behring /Nycomed

Beriplast

Liquid

£200

Human/Animal

Preparation Time – 15-20 mins*** Application Time – 1-2 mins

Low(Strength)

Haemostat action greater than sealant effect

Ethicon/Omrix

Quixil/ Crosseal

Liquid

£200

Human

Preparation Time – 15-20 mins*** Application Time – 1-2 mins

Low(Strength)

Haemostat action greater than sealant effect

CryoLife

BioGlue

Liquid

£190

Animal

Preparation Time – 2-3 mins Application Time – 1-2 mins

Low(Weak adhesion)

Cytotoxicity concerns relating to glutaraldehyde component

Nycomed

Tachosil / Tachocomb

Sheet

£209

Human/Animal

Preparation Time – 2-3 mins ** Application Time – 3-5 mins **

Medium(Slow/Weak adhesion)

Poor surfaceconformance

Thermogenesis

CryoSeal

Liquid

£160

Autologous

Preparation Time – 60 mins** Application Time – 1-2 mins**

Low(Strength)

Requires processing unit to convert patients blood to product

Vivolution

Vivostat

Liquid

£160

Autologous

Preparation Time – 30 mins** Application Time – 1-2 mins**

Low(Strength)

As CryoSeal

Confluent Surgical

DuraSeal

Liquid

£220

Synthetic

Preparation Time – 1-2 mins Application Time – 1-2 mins

Low(Strength,Short duration)

Genzyme

FocalSeal

Liquid

£180

Synthetic

Preparation Time – 2-4 mins*** Application Time – 5-10 mins

Low(Strength/Short duration)

Tissuemed

Tissuepatch3

Film

£200

Synthetic

Preparation Time – 0 mins Application Time – 30 secs/patch

High (Contact surface chemistry, duration of effect)

* Equivalent per 5cm x 5cm patch ** Company information

Requires light source

*** Report entitled Topical Hemostats in Surgery; Mary Jo Drew MD 2003

All liquid sealants require applicators or spray systems…..prices not included as this may be provided Free of Charge General comment: Unlike Tissuepatch3 none of the listed products, excluding FocalSeal, was originated based on the lung application, which explains their generally low acceptance.

Fibrin-based Liquids(Tisseel, Beriplast, Quixil) •Typically require “mixing” up to 20 minutes prior to application •Need time (1-2 minutes) to work •Have low intrinsic strength •Require careful application and may be difficult to apply uniformly to target tissue •Are derived from human/animal sources •Have a haemostatic rather than adhesive sealant effect

Synthetic Liquids (Duraseal, Focalseal) •Typically require “mixing” a few(1-2) minutes prior to application •Need time to apply (Focalseal – 5-10 minutes) and work (1-2 minutes) •Have low intrinsic strength •Require careful application and may be difficult to apply uniformly to target tissue •Have low duration of effect because of their chemistry •In the case of Focalseal requires a Light source to activate.

Autologous “sealants” (Cryoseal, Vivostat) •Require extended preparatory process involving blood removal from patient 30-60 minutes prior to application •Need time (1-2 minutes) to work •Have low intrinsic strength •Require careful application and may be difficult to apply uniformly to target tissue •Have low adhesion, acting primarily as haemostats •Requires significant hardware

Sheet-type haemostats (Tachosil,Tachocomb) •Require preparation (2-3minutes) •Need time (3-5 minutes) to work •Are derived from human/animal proteins •Have low adhesion •Are bulky and have poor “conformability”

Questions and Answers What is Tissuepatch3? Tissuepatch3 is a self adhesive surgical sealant and barrier. It is a thin flexible film supplied in three sizes; small (25mm × 50mm), medium (50mm × 50mm) and large (50mm × 100mm). Tissuepatch3 is 40 microns (0.04mm) thick. What procedures is Tissuepatch3 indicated for?

Tissuepatch³ is indicated for use to seal and reinforce against air leakage in thoracic surgery, and against leakage of low pressure or oozing bleeding or fluid leakage following surgical procedures on soft tissue. Tissuepatch³ is intended for use as an adjunct in thoracic and general surgery and is not intended to replace sutures or staples, as appropriate, in tissue approximation. How does Tissuepatch3 work? Upon application Tissuepatch3 immediately adheres to the surface by a combination of electrostatic and covalent bonding. How adhesive is Tissuepatch3? The adhesive strength of Tissuepatch3 is significantly higher (×100) than that of commonly used haemostats (e.g. Tisseel) and sealants (e.g. CoSeal).

Questions and Answers Does Tissuepatch3 contain animal/human derived material? No – Tissuepatch3 is entirely synthetic. What are the storage conditions for Tissuepatch3? Tissuepatch3 should be stored at 2-8°C. It should not be frozen. The product currently has a shelf life of 17 months. How is Tissuepatch3 packaged? For each product size, a single device is packaged within a sterile paper/plastic inner pouch, which is further sheathed in an outer foil pouch the outside of which is NON-STERILE. Can Tissuepatch3 be cut to shape? Yes – Tissuepatch3 can be cut to shape with sterile scissors. Handling, especially of the contact surface should be minimised and it should be kept dry. Should Tissuepatch3 be applied dry or wet? Tissuepatch3 should remain dry until applied. Wetting will affect adhesion performance.

Questions and Answers How should Tissuepatch3 be applied? Before application the site should be wiped to remove excess blood/fluid. With the “TP 3” text readable, pressure should be exerted across the patch using a dry swab for at least 30 seconds. Can Tissuepatch3 be removed? If Tissuepatch3 has been applied incorrectly or has not adhered it may be removed within the first few minutes of application. The tissue may be prepared for application of a new patch. How large a patch should I use? During application there should be a 1cm margin between the injury and the edge of the Tissuepatch3 applied. When treating large injuries Tissuepatch3 may be overlaid. Is there a limit to how many patches can be applied? Preclinical data supports the safe use of up to 8 small (25mm × 50mm × 0.04mm), 4 medium (50mm × 50mm × 0.04mm) and 2 large (50mm × 100mm × 0.04mm) patches.

Questions and Answers Can Tissuepatch3 be resterilised? No – Tissuepatch3 is a sterile single patient use medical device. Once opened Tissuepatch3 should be kept dry and used within 6 hours, after which it should be discarded. Can Tissuepatch3 be removed? If Tissuepatch3 has been applied incorrectly or has not adhered it may be removed within the first few minutes of application. The tissue may be prepared for application of a new patch. Are there any contra-indications for use? Tissuepatch3 should not be used on patients with a known allergy to its constituents. It should not be used to seal defects in neurological applications. It is not for intravascular use. What is the “TP 3” logo for? Tissuepatch3 should be applied so the “TP 3” logo can be read. Is Tissuepatch3 biodegradable? Tissuepatch3 remains in position covered in a thin fibrous cover and it slowly degrades until resorbed in ≈ 50 days.

In conclusion…..a few soundbites •Because of its construction and contact surface chemistry Tissuepatch3 is the most effective product available for prevention of air leakage in lung surgery •Tissuepatch3 requires no advance preparation, mixing, soaking or extended contact apposition…..it requires the least amount of preparation and application time of all available products, being truly “open and apply” •Tissuepatch3 is the easiest product to handle and apply to the target tissue.