1. Stem cells and materials technologies
Group 16 - Biomaterials and waste treatment
Ciência 2009, 29-30th July 2009, Lisbon

2. Strategic Intent
To target clinical needs through the integration of advanced adult stem cell biology and novel biomaterials into innovative therapeutic products for tissue regeneration

3. History Academic spin-off of the 3B’s Research Group
Created in November, 2007
Installed since September 2008 at the European Institute of Excellence for Tissue Engineering and Regenerative Medicine Research, Guimarães, Portugal.
Equipped with a future cGMP compliant facility for the processing of human tissue and cells (2003/94/EC Directive):
300 m2 of clean room (classes B, C and D);
250 m2 of R&D and QC laboratories.
1st funding round estimated to be finished by Sept, 2009
Start of operations estimated by Oct, 2009

4. Team
CSO: Rui L. Reis, CEng., MSc., PhD. (n. 1968) – Founder, President and Chief Scientific Officer: is an Associated Professor at the Department of Polymer Engineering and Director 3B’s Research Group. Editor in Chief of the Journal of Tissue Engineering and Regenerative Medicine, John Wiley and Sons Inc. He is author or co-author of more than 900 scientific publications.
CEO: Rui A. Sousa, CEng., MBA., PhD. (n. 1974) – Chief Executive Officer: is a senior researcher at the 3B’s Research Group. Possesses business experience in several industrial and consultancy domains. He is author or co- author of more than 90 scientific publications and communications.
Dulce Costa
Luísa Pereira
João Oliveira
Adrian Popa

5. Social Context
The WHO estimates that more than 600 million people are aged above 60, being estimated that this number reaches the 2 billion by 2050.
Growing impact of degenerative or traumatic conditions due to demographic evolution, more dynamic lifestyles, and increased physical activities.

6. Regenerative Medicine
Overall Market
Regenerative Medicine 2 1 3 5
Adaptado de Julian H S George et al 4

7. Use of stem cells from adipose tissue
More than 1.6 billion people are overweight, of which 400 million are considered obese, with treatment costs between 2 and 8% of total health costs.
Steep increase in aesthetical surgical procedures, being Europe responsible for about one third of this global market.

8. Business Portfolio Stemmatters Therapeutics Stemmatters Life Banking
Stemmatters Biomedical

9. Stemmatters Therapeutics

10. The Market for Cartilage Regeneration
Current Markets
The Market for Cartilage Regeneration
Prevalence of articular cartilage related lesions in Europe
Nearly traumatic incidents occur;
About 7 million cases of treatable arthrosis occur each year.
High market potential for cartilage regeneration
Among the biggest markets for connective tissues, being estimated between 1 to 5 billion €/year in Europe alone.
Very high penetration of traditional treatment approaches
Arthroscopic lavage and debridement, microfracture and mosaicplasty rule the treatment of cartilage lesions.
Cell based therapies with reasonable track record in this area
ACT and MACI procedures are considered market references.

11. Products Under Development
Product Pipeline
Products Under Development
Types of products currently under development:
ATMPs (Advanced Therapy Medicinal Products)
G01AT110C | pre-clinical | RECART Hydrogel/Adipose derived adult stem cells
G01AT300A | research | Hydrogel/Vascular stromal fraction derived cells
MDs (Medical Devices)
G01MD210B | research | Injectable filler for soft tissue applications
G01MD250B | research | Injectable filler system for maxillofacial applications

12. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
Combined advanced therapy medicinal product (1394/2007 Regulation, CBMP EMEA guideline)
Polysaccharide hydrogel as an active implantable device
Exopolysaccharide produced by microbial fermentation:
Straight chain of repeating glucose, rhamnose and glucuronic acid units;
Potential injectable system for minimally invasive surgeries;
Processing under physiogical conditions without any reagents;
Used in vivo for human ophthalmic applications and oral veterinary drug delivery.
Adipose derived adult stem cells
Isolated from harvested adipose tissue:
Dedicated or non-dedicated harvest procedure;
Subpopulation isolated from the stromal vascular fraction;
Good cell yield avoids previous cell expansion.

13. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
Novel hydrogel system for TE applications
J.T. Oliveira et al, Patent Application

14. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
Good performance upon subcutaneous implantation
1 WEEK
2 WEEKS
3 WEEKS
No clear macroscopic change after 3 weeks of implantation.
Extremely good integration with the surrounding tissues with a residual and thin fibrotic capsule.

15. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
8 WEEKS
Human chondrocytes form hyaline-like cartilage in vitro
Col1 was not detected after 8 weeks
Col2 increased ≈ 400 fold from 2-8 weeks
Aggrecan increased ≈ 35 fold from 2-8 weeks
Sox9 decreased close to zero from 2-8 weeks
house-keeping gene: GAPDH

16. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
ADIPOSE TISSUE FROM THE INTRASCAPULAR REGION
ARTICULAR CARTILAGE FROM THE JOINTS
CHONDROGENIC PRE ≠ MEDIUM WITH TGF-Β1 + BMP-2
BASIC MEDIUM WITH NO PRE ≠
PROLIFERATION INDUCING MEDIUM WITH FGF-2

17. full-thickness defect
Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
Implantation site
Rabbit articular cartilage
Articular cartilage
full-thickness defect
Subchondral drill
(Ø 1 mm)
(4 mm x 2-3 mm thickness)
Study groups
A. Gellan + adipose tissue derived cells with pre differentiation period (ASC + GF*)
B. Gellan + adipose tissue derived cells with no pre differentiation period (ASC)
C. Gellan + articular chondrocytes (AC)
D. Gellan alone (GELLAN)
E. Empty defect (EMPTY) + + +
*TGF-Β1 + BMP-2
Autologous approach
Total implantation time: 8 weeks
[Cells]=10x106 cells/ml
Characterization
Macroscopic observation
Histology (H&E for cell morphology and tissue formation and alcian blue for cartilage ECM formation)
Histological scoring (Pineda score)
Real-time PCR analysis (Sox9, Collagen type I, Collagen type II, and Aggrecan)
J.T. Oliveira et al,
Patent Application

18. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
0 weeks
4 weeks
8 weeks
Combination of hydrogel with ASCs is able to regenerate focal cartilage lesions
J.T. Oliveira et al, Patent Application
Patent Application/Priority date:

19. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells

20. Product Pipeline
Stemmatters Therapeutics | RECART Hydrogel/Adipose derived adult stem cells
Advantages of the cartilage repair strategy include:
Potential therapeutic performance
Minimally invasive system to be administered arthroscopically
Avoids the need for a cartilage biopsy
Shorter time to therapy (TTT)
Competitive cost as compared to traditional ACT and MACI procedures

21. Competition Tissue Engineering Products Primary cells Progenitor cells
Cartilage application
Arthro Kinetics, BioTissue Technologies, Cellgenix, co.don, Curasan, Educell, Fidia Advanced Biopolymers, Geistlich Surgery, Genzyme Biosurgery, Histogenics, Interface Biotech, Karocell Tissue Engineering, Orthogen, TIGenix, TETEC, Verigen Transplantation Service International
Cartilage: application
Stemmatters (Autologous)
Bone application
Aastrom Biosciences (Autologous),
Osiris Therapeutics (Allogeneic)
Skin application
Organogenesis, BioTissue Technologies, Advanced BioHealing, Inc., Genzyme Biosurgery, Fidia Advanced Biopolymers, Intercytex, Celltran, Forticell Bioscience, Cambrex
Primary cells
Progenitor cells
Cartilage application
Osiris Therapeutics (Allogeneic)
Several applications:
Advanced Cell Technologies, Geron, ES Cell International, Stem Cell Sciences, Aastrom Biosciences, Aldagen, Angioblast Systems, Athersys , BrainStorm Cell Therapeutics, Cardio3, Cellerant Therapeutics, Cognate Therapeutics , Gamida-Cell, Mesoblast , Neuronyx, Osiris Therapeutics, AdiStem, Bioheart, Cellerix, Cognate Therapeutics, Cytori Therapeutics , ReNeuron Group Plc, Tengion, PharmaFrontiers , Tissue Genesis, Inc , Gamida-Cell, Saneron CCEL Therapeutics, ViaCell
Cartilage application
co.don, Educell, Geistlich Surgery, Genzyme Biosurgery, Interface Biotech, TIGenix, TETEC
Other Cell
Based Therapies

22. RECART Hydrogel/Adipose derived adult stem cells
Product Pipeline
RECART Hydrogel/Adipose derived adult stem cells
R&D and non-clinical development
Clinical development
MA Applic.
Marketing Authorization
Biomaterial R&D
Phase I
In vitro testing
Phase II
Phase III
In VivoTesting
GMP grade
Phase IV
2019
2020

23. RECART Hydrogel/Adipose derived adult stem cells
Product Pipeline
RECART Hydrogel/Adipose derived adult stem cells
R&D and non-clinical development
Clinical development
MA Applic.
Marketing Authorization
Biomaterial R&D
Phase I
In vitro testing
Phase II
Phase III
In VivoTesting
GMP grade
Phase IV
Stemmatters Life Banking
Stem cell isolation and storage services
Stemmatters Biomedical
Products and services for R&D
2019
2020

24. Contacts Rui A. Sousa CEO Tel. +351-253-540100 Fax. +351-253-540199

25. Stemmatters Life Banking

26. Main application markets for stem cells
Current Markets
Main application markets for stem cells
Current uses of stem cells are made in 3 distinct medical related markets:
Cell banking;
Therapeutic development;
Cell therapies.
(source: Frost & Sullivan).

27. Stemmatters Life Banking | Stem cell isolation and storage services
Current Offering
Stemmatters Life Banking | Stem cell isolation and storage services
Bone marrow (onstem service – B2C);
Adipose tissue (adstem service – B2C):
The treatment of tissues and biological residues generated in surgical procedures assures a cell banking opportunity not yet addressed.
Market potential for the isolation and storage of adipose derived adult stem cells for autologous application is estimated to worth:
75 million €/year for Spain, France, Germany, UK, Italy and Portugal;
120 million €/year for EU15.
Assures a polyvalent platform for regenerative technologies;
Assures positive cash flow and supports leveraging of R&D pipeline.

28. Stemmatters Life Banking | Stem cell isolation and storage services
Competition
Stemmatters Life Banking | Stem cell isolation and storage services
Newborns
Children
Adults
Europe
Crioestaminal, Bioteca, Bebé Vida, Criovida, Cytothera (Portugal)
Celvitae, Vidacord, Secuvita, Vidaplus, Stem Cell, CrioCord, Safetycord (Spain)
ActiVision Life (Poland), Babycord (Cyprus), Babycord (Turkey), Biohellenica (Greece), Biophylaxis (Greece), BPK (Slovenia), CopyGene (Denmark), CryoBank (Turkey), Cryo-Save (Belgium), Cryomedica (Russia), Eticur (Germany), Eurocord (Slovakia), Floramed (Russia), Gemabank (Russia), GenKord (Turkey), Hemafund (Ukraine), In Scientia Fides (Italy), Krio (Hungary), Liaison (Greece), LifeBank (Cyprus), Lifecord (Austria), Lifeline (Cyprus), LongaVita (Poland), Polish Stem Cell Bank (Poland), Progenis (Poland), RCB (Switzerland), Seracell (Germany), SmartBank (Italy), StellaCure (Germany), Stemcare (Denmark), Stem-Health Hellas (Greece), VITA34 (Germany), Vitacord (Austria), Yasam Bankasi (Turkey), Cells4Life (UK), Cells Limited (UK), CryoGENESIS (UK), Future Health Technologies (UK), SmartCells (UK), UK Cord Blood Bank (UK), UK Health Solutions (UK), Virgin Health Bank (UK)
Bioeden (UK)
Stemmatters
Cytothera (Portugal)
Cryo-Save (Belgium)
Cytori Therapeutics
Biohellenika (Greece)
USA
AlphaCord, CordBancUSA, Cord Blood America, Cord Blood Registry, Cord Blood Solutions, Cryobanks International, Cryo-Cell International, DomaniCell, Elie Katz, Family CB Services, Family Link, Genesis Bank, HemaStem, LifebankUSA, LifeLine, LifeSource, MAZE Labs, Neocells, Newborn Blood Banking, New England CB Bank, RMI, Safetycord, Securacell, StemCyte, Stork Medical, Utah Cord Bank, Viacord, Vista Cord, Xytex
Bioeden, StemSave, Baby Teeth Cell Bank
Cryo-cell
Neostem

29. Stemmatters Life Banking | Stem cell isolation and storage services
Current Offering
Stemmatters Life Banking | Stem cell isolation and storage services
Acquisition Drivers
Increased value of the surgical procedure;
Potential application in future autologous regenerative therapies;
Allows for off the shelf availability of personalized regenerative products;
Decreases time for clinical delivery of therapy.
Current applications of adipose derived adult stem cells
Radiation Necrosis
Breast Reconstruction
Heart Attack
Chronic Heart Disease
Crohn’s Disease
Tracheal Fistula Healing
Calvarial Repair
Marrow Transplant Complications
Diabetes

30. Stemmatters Biomedical

31. Stemmatters Biomedical | Products and services for R&D
Current Offering
Isolation and processing services of human cells:
Human stromal vascular fraction isolated from adipose tissue containing human adipose derived stem cells (all samples are characterized for cell number and viability);
Human adipose derived stem cells (all samples are characterized for cell number and viability, as well as multipotent mesenchymal stem cell markers: CD29, CD105, CD34 and CD45);
Pre-clinical research in regenerative medicine accounts for a market volume of about 700 million €/year.
Cell culturing products;
Hydrogel support systems for 3D cell culturing;
Very high R&D visibility among the potential buyer community;
The global market potential for the commercialization of 3D supports for non-clinical R&D is estimated to worth between 7 and 35 million €/year.
Device for dynamic cell seeding and culturing.
Stemmatters Biomedical | Products and services for R&D

32. Corporate Strategy

33. Corporate Strategy

34. Financial projections

35. Financial Projections