1

CEO’s PresentationASX Announcement 12th November 2012Tissue Therapies Limited ABN 45 101 955 088

Announcement At the Annual General Meeting of Biomedical company, Tissue Therapies Limited (ASX: TIS) held on 12 November 2012, the following CEO’s presentation was delivered to the audience. Please see the PDF of the powerpoint presentation on the following pages.

For

per

sona

l use

onl

y

Tissue Therapies Ltd AGM CEO Presentation 12 November 2012

Commercialising VitroGro® ECM A Revolution in Wound Healing

Dr Steven Mercer, CEO

For

per

sona

l use

onl

y

Tissue Therapies Limited

AGM CEO Presentation

2

!   Introduction

!   VitroGro® ECM

!   Clinical Effectiveness: – Wound Healing – Pain Reduction

!   Economic Effectiveness

!   Market Size

!   Sales Estimates

!   Commercial Partners

!   CE Mark

!   Revised EU Launch

!   Rest of World (ROW) Timelines

!   USA Clinical Trials, Approval and Launch Timelines

!   Summary

For

per

sona

l use

onl

y

Tissue Therapies Limited

Introduction

Tissue Therapies:

!   An Australian biomedical company developing advanced technologies for more cost effective wound healing, tissue repair, cell culture and other global applications

!   Worldwide exclusive rights to commercialise VitroGro®technology: first product – VitroGro® ECM for difficult to heal wounds

!   Patents granted in the USA, Europe, China, Hong Kong, South Korea, Japan, South Africa, Australia and New Zealand (pending applications in Canada & India)

!   CE Mark (EU) approval expected 2013: immediate sales launch in UK, Germany, Switzerland, Austria, the Netherlands and Nordic countries

!   Approved EU claim is for treatment of difficult to heal wounds: broad on-label use

!   Partnerships with Quintiles (hiring & support services) and Movianto (logistics) that minimise operational risk, restrain cost and optimise revenue

!   Attractive margin product; more convenient, consistent and cost effective than existing wound care treatments

!   USA FDA trials scheduled to start 2013

3

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM

What is VitroGro® ECM

VitroGro®  ECM  is  a  synthe2c,  extra-­‐cellular  matrix  (ECM)  protein  crea2ng  a  physical  structure  (a  scaffold)  that  binds  to  the  wound  bed

!   Restores  aCachment  sites  in  skin  &  guides  cells  during  wound  healing  

!   Diabe2c  (DFU),  Venous  (VLU)  &  Pressure  Ulcers  are  primary  markets  

!   Addressing  a  significant  un-­‐met  need  in  providing  a  convenient,  cost  effec2ve  treatment   –  improved  healing,  only  1  applica2on  per  week  x  10  weeks  – Correc2on  of  wound  2ssue  pathology  by  delivery  of  biologically  appropriate  matrix  

!   Scale  up  manufacturing  complete;  VitroGro®  ECM  in  warehouses  ready  to  ship    

4

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM

Additional indications / market segments  

VitroGro®  ECM  can  also  be  used  to  address:  

!   Burns:  Paediatric  &  Adult  !   Surgical  Wound  Applica2ons  (especially  at-­‐risk  

pa2ents)  

!   Specialist  Units  &  Retail    –  Specialist  unit,  general  hospital,  outpa2ent,    GP,  pharmacy,  retail    

– Poten2al  retail  applica2ons  include  dressings,  creams,  lo2ons,  product  range  for  burns,  chronic  wounds,  acute  sunburn  etc.  

5

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: Principle of Operation

6

1 2

3 4

VitroGro® ECM replaces the degraded matrix of the hard-to-heal wound providing a physical structure (a scaffold), for cell attachment. This process is vital for subsequent cell functions that are critical for healing.

For

per

sona

l use

onl

y

Tissue Therapies Limited

Clinical Effectiveness: Wound Healing

EU clinical trial : Venous Leg Ulcer (VLU) study

In human trials, VitroGro® ECM has demonstrated consistent and convenient healing of venous, diabetic and pressure ulcers that had not responded to expert care

!   Results: –  Trial patients were relatively old (average age 72 years) and had suffered venous ulcers

that had not responded to expert care for an average of 36 months –  Strong results: 34 % completely healed & 42% more than 90% healed within 12 weeks

7

Wound area reduction in 45 patientstreated with VitroGro® ECM over 12 weeks*

Wound area reduction (%) * Prior to treatment, patients had no response to 4 weeks of standard care

>90% - 100% >70% - !90% >50% - !70% >20% - !50% Not improved

20

18

16

14

12

10

8

6

4

2

0

Numb

er of

patie

nts

42%

11% 11%16%

20%

For

per

sona

l use

onl

y

Tissue Therapies Limited

Clinical Effectiveness: Pain Reduction

Reduction of patients’ pain is important

!   Improved  pain  management  outcomes  during  healing  delivers  pa2ent  and  health  economic  benefits.  

8

100

71.4 66.7

0

28.6

20.0

0 0

13.3

0

10

20

30

40

50

60

70

80

90

100

severe pain (6 patients) moderate pain (7 patients) mild pain (15 patients)

% o

f pat

ient

s

Pain category at baseline (VAS) scale

Change in pain of patients grouped by baseline pain category

% reduction to no pain

% no change in pain

% Increased pain

Jensen M., Chen C., Brugger A. Interpretation of visual analog scale ratings and scores: a reanalysis of two clinical trials of postoperative pain. Pain. 2003: Sep 4 (7): 407-414

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM Economic Effectiveness

Preliminary UK economic modelling:

!   VitroGro® ECM cost reduction of 22% in the clinic setting and 32% in community care setting for a treatment period of 12 weeks.

!   Many ulcers do not heal promptly when managed using current standard of care treatment. –  Up to 50% of venous ulcers may be

present for 7 to 9 months and between 8% and 34% may be present for more than 5 years

–  For this reason it is appropriate to show the cost comparison between using VitroGro® ECM and managing a non-healing ulcer with standard of care for a duration of one year.

!   51% saving for the cost of treatment for a non healing ulcer with a duration of 1 year

9

For

per

sona

l use

onl

y

Tissue Therapies Limited

Global Market

Global venous, diabetic and pressure ulcer market in 2008

Global market is growing rapidly:

!   In 2008, the market size was estimated at US$14 Bn & growing at ~15% per annum

!   Multiple publications now suggest true market size is US$30 – 40 Bn (refer publications, Appendix)

!   Growth driven by an aging population, increasing incidence of venous disease & diabetes as well as expanding affordability of health care, primarily in developing countries

!   Further potential in consumer, retail and acute wound care products

10

42%  

22%  

36%  

USA  /  Canada  

UK  /  Europe  

Rest  of  World  

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: Sales Estimates

VitroGro® ECM sophisticated sales modelling: diabetic, venous & pressure ulcers

!   Ini2al  focus  on  UK,  German  speaking  Europe,  the  Netherlands,  Nordic,  then  ROW  and  FDA    

!   Cost  compe22ve,  convenient,  consistent  healing  versus  exis2ng  treatments  

11

0 100 200 300 400 500 600 700 800

2013

2014

2015

2016

2017

2018

2019

Revenue in USD (millions)

Cal

enda

r Yea

r

Revenue projection (USD) per market size phased with start of sales

USA

Europe

Rest of World

71 million

675 million

460 million

358 million

209 million

22 million

0.4 million For

per

sona

l use

onl

y

Tissue Therapies Limited

Commercialisation: Partnership Structure

Tissue Therapies has in place partnerships that minimise operational risk, restrain cost and optimise revenue while maintaining flexibility and control

12

!   Quin&les  –  Outsourced  HR  for  dedicated  VitroGro®  ECM  Sales  team;  shared  risk/reward:  KPI  based  fee  structure  

!   Movianto    –  Integrated  Logis2cs,  Mul2-­‐lingual  Customer  Support,  Order  Entry,  Supply,    Accounts  Receivable    

 

!   Eurogentec  –  Manufacture  of  VitroGro®  ECM  Protein    

!   Catalent  –  Fill,  finish  &  release    

!   Queensland  University  of  Technology  (QUT)  –  Research  &  Development;  only  royalty  payable  to  QUT  

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: CE Mark

!   Notification of CE Mark approval received July 2012: now expected 2013

!   New MHRA requirement for European Medicines Agency (EMA) review of manufacturing and quality data: statutory maximum 210 calendar days

!   Delay in EU sales, but compensating factors from EMA review: –  EMA review completes all possible regulatory requirements –  Result will be definitive regulatory approval for sale signed off by all EU member countries –  Stronger, more comprehensive VitroGro® ECM regulatory package for approval for sale in

Turkey, Middle East, Latin America, Russia, Taiwan, Canada and Australia

!   EMA review period will be used to: –  Prepare for earlier sales launches in: Nordic countries, Middle East, Turkey, Latin America

& Russia: bring revenue forward –  Finalise and lodge FDA applications for venous and diabetic ulcer trials

!   EMA submission is Common Technical Document; well understood format and submission substantially complete

!   EU sales will start within 1 business day of CE Mark being granted

13

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: Revised EU Launch

2013 United  Kingdom,  Benelux,  Austria  Germany,  Switzerland,  Northern  Italy,  Sweden*  Denmark*  Finland*,  Norway*  

*  Brought  Forward    

2014 Hungary*,  Czech  Republic*,  Poland*,  (plus  Russia*,  Turkey*,    UAE*,  Saudi  Arabia*,  Bahrain*)  

*  Brought  Forward    

2015 France  (clinical  data  from  FDA  trial  for  reimbursement)  

14

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: Germany, Austria, Switzerland

15

Market preparation

!   12  months  work  with  most  influen2al  KOL’s  

!    Health  economics  project  with  German  data  

!   Publica2ons  planned  based  on  clinical      results  and  health  economics  

!   German,  Austrian,  Swiss  wound  care      expenditure  x  2.5  UK:  €3  Bn  in  2009  

! 800  specialist  wound  care  private  clinic      network  

Sales strategy

!   launch  immediately  amer  CE  Mark  

!   Immediate  sales  to  10  most  influen2al  clinics:  pyramid  rollout  

!   Private  Insurance:  10%  popula2on:  KOL  led  assessment  of  50  pa2ents.    Guideline  doc  for  private  insurance  applica2on:  approval  target  2014  

!   Public  reimbursement:  90%  popula2on:  Accelerated  137e  Review,  target  approval  2014:  VitroGro®  ECM    purchased  for  approx.  550  pa2ents.    Earlier  approvals  of  smaller  40  pubic  reimbursement  agencies  during  137e  Review  

35  

5  4  10  

3  11  8  

1   5  7   11  

German  %  Share  of  Global  VLU  and  DFU  market    

USA  

UK  

France  

Germany  

Nordic  

Japan  

China  

India  

Brazil  

Canada  

Rest  of  World  

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: United Kingdom

16

35  

5  4  10  3  11  8  1   5  

7   11  

UK  %  Share  of  Global  VLU  and    DFU  Market      

USA  

UK  

France  

Germany  

Nordic  

Japan  

China  

India  

Brazil  

Canada  

Rest  of  World  

Market preparation

!   NHS  expenditure  on  wound  care  >  £1  Bn  in  2009*  

!   12  months  work  with  most  influen2al  key    opinion  leaders  (KOL’s)  

!   Health  economics  analysis:  data  ready  now  

!   Prepara2on  for  journal  adver2sing  

!   Publica2ons  wriCen  with  UK  experts  

!   72  PCT  Wound  Care  Clinics  generate  >  80%  of  wound  care  expenditure  

Sales strategy

!   UK  launch  immediately  amer  CE  Mark  

!   Sampling  program  to  key  72  specialist  wound  clinics  

!   Applica2on  for  Drug  Tariff  inclusion  (pharmacy  access)  

!   Immediate  sales  to  PCT  wound  clinics:  formulary  discre2on  

* Madden, M. “Alienating evidence based medicine vs. innovative medical device marketing: A report on the evidence debate at a Wounds conference.” In press Social Science & Medicine xxx (2012) 1e7

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: Rest of World

17

ROW* Sales Timeline

2013 !   Finalise & lodge planned

applications for sale in ROW countries

!   Finalise sales & distribution channels

2014 !   Sales: CE Mark

Recognition: –  Russia, Turkey, Middle East,

Latin America, Australia, South Africa

!   Sales: Independent Approval Process: –  China, Hong Kong, South

Korea, Taiwan, Japan, SE Asia, India

(* ROW = all countries outside EU & North America)

For

per

sona

l use

onl

y

Tissue Therapies Limited

VitroGro® ECM: USA

18

Market preparation

!   Largest  single  global  market:  US$15.3Bn  in  2010*  

!   18  months  work  with  KOL’s,  Chief  Clinical  Inves2gator  &  Clinical  Research  Org.  

!   Venous  &  diabe2c  ulcer  trial  protocols  complete  

!   All  clinical  trial  sites  iden2fied  including  reserve  sites  

!   Almost  en2re  market  is  reimbursement  based  100%  popula2on  coverage  

!   FDA  Biologics  classifica2on;  prac2cal  benefits  in  clinical  trials  &  reimbursement  

Sales strategy

!   Complete  VLU  trial  2014  &  DFU  2015:  15  months  for  approval  &  reimbursement:  Sales  2016  

!   Single  reimbursement  nego2a2on  with  Centers  for  Medicare  &  Medicaid  Services  (CMS):  avoids  device  reimbursement  nego2a2ons  with  all  private  insurance  payers  

!   Extended  health  economics  based  on  US  data:  agreement  with  hospital  network  

!   Decision  on  North  American  fill  /  finish  /  release,  logis2cs,  sales,  customer  service  

!   Sampling  program  

35  

5  4  10  3  11  8  

1   5  7   11  

USA  %  Share  of  Global  VLU  and  DFU  Market        

USA  

UK  

France  

Germany  

Nordic  

Japan  

China  

India  

Brazil  

Canada  

Rest  of  World  

*  Sen  KS,  Gordillo  GM,  Sashwa2  R,  Kirsner  R,  Lambert  L,  Hunt  TK,  GoCrup  F,  Gurtner  GC,  Longaker  MT.  Human  Skin  Wounds:  A  Major  and  Snowballing  Threat.  Wound  Repair  Regen.  2009  ;  17(6):  763–771.

For

per

sona

l use

onl

y

Tissue Therapies Limited

Tissue Therapies Summary

!   Global exclusive rights to commercialise VitroGro® ECM: multiple large and fast growing markets – unmet need

!   European CE Mark approval expected 2013 allowing transition into commercialisation phase; sales in EU and ROW countries brought forward from original launch plan

!   USA FDA trials commencing in 2013 with North American sales to follow

19

0 100 200 300 400 500 600 700 800

2013

2014

2015

2016

2017

2018

2019

Revenue in USD (millions)

Cal

enda

r Yea

r

Revenue projection (USD) per market size phased with start of sales

USA

Europe

Rest of World

71 million

675 million

460 million

358 million

209 million

22 million

0.4 million

For

per

sona

l use

onl

y

Tissue Therapies Limited

Disclaimer

!   This document has been prepared by Tissue Therapies Ltd (the Company) to provide existing and prospective investors in Tissue Therapies Ltd with an update on the Company and its operations

!   The information contained in the presentation is not intended to be an offer for subscription, invitation or recommendation with respect to shares in any jurisdiction.

!   No representation or warranty, express or implied, is made in relation to the accuracy or completeness of the information contained in this document or opinions expressed in the course of this presentation. The information contained in this presentation is subject to change without notification.

!   This presentation contains forward-looking statements which can be identified by the use of words such as “may”, “should”, “will”, “expect”, “anticipate”, “believe”, “estimate”, “intend”, “scheduled” or “continue” or similar expressions. Any forward-looking statements contained in this presentation are subject to significant risks, uncertainties, assumptions, contingencies and other factors (many of which are outside the control of, and unknown to, Tissue Therapies Ltd (“TIS”) and its officers, employees, agents or associates), which may cause the actual results or performance to be materially different from any future result so performed, expressed or implied by such forward-looking statements.

!   There can be no assurance or guarantee that actual outcomes will not differ materially from these statements.

!   The photographs of clinical subjects used in this presentation are illustrative of medical conditions associated with potential applications of VitroGro®. Actual clinical results may vary from those shown.

20

For

per

sona

l use

onl

y

VitroGro® ECM: Product Ready

21

For

per

sona

l use

onl

y

2

CEO’s PresentationASX Announcement 12th November 2012Tissue Therapies Limited ABN 45 101 955 088

Tissue Therapies Limited ABN 45 101 955 088 Level 19, 179 Turbot Street, Brisbane, QLD 4000 Australiawww.tissuetherapies.com

What is VitroGro® ECM

• VitroGro® ECM is a topically applied, biomimetic scaffold, comprising a synthetic extracellular matrix (ECM) protein.

• How it works: VitroGro® ECM replaces the degraded matrix of a hard to heal wound. VitroGro® ECM binds to a prepared wound bed and provides a physical structure (a scaffold) for cell attachment, which is a primary requirement for subsequent cell functions critical for healing, such as cell proliferation and migration [1].

• An optimal scaffold: Oneofthecharacteristicsofhardtohealwoundsisprolongedinflammation,whichdamages the native ECM that would normally guide the wound healing process [1,2,3,4]. Replacement ofthisdamagedECMisabeneficialstrategyfortreatinghardtohealwounds [1]. VitroGro® ECM is ideal as an ECM replacement since its structural and functional elements mimic those present in the ECM at the early stages of normal wound healing.

• Expert health economics modelling indicates that VitroGro® ECM offers the opportunity for substantially more cost effective treatment of wounds compared to the current standard of care.

[1] Widgerow AD . Deconstructing the stalled wound. Wounds 2012

[2] Schultz GS. Extracellular Matrix: review of its roles in acute and chronic wounds. World Wide Wounds. 2005

[3] MoorAN.etal.Proteolyticactivityinwoundfluidsandtissuesderivedfromchronicvenouslegulcers.WoundRepReg.2009

[4] International consensus, Acellular matrices for treatment of wounds. Wounds Int. 2010

About Tissue Therapies Limited

TissueTherapies Limited is abiomedical technology company that is developing significantlymoreeffective treatments for acute and chronic wound healing applications, including chronic skin ulcers and burns. Tissue Therapies Limited is commercialising VitroGro® ECM, a technology created by cell biology, tissue engineering and protein engineering experts at the Institute of Health and Biomedical Innovation at the Queensland University of Technology. The company is also developing treatments for psoriasis, scar prevention and various cancers including those of the breast, colon and prostate. Tissue Therapies Limited’s shares are traded on the Australian, Berlin and Frankfurt stock exchanges.

More information: www.tissuetherapies.com

For

per

sona

l use

onl

y