SilkBiomaterials Investors Deck

1. A tissue engineering company developing the first fibroin-made tissue engineered graft
for vascular procedures (i.e.: artery bypass, peripheral revascularization, etc.)
SilkByPass will help patients regenerate new biological blood vessels

2. A $4bn+ market
opportunity in the
CABG market alone
An extremely low cost
manufacturing process
The ultimate solution
for vascular prostheses
& tissue regeneration
A breakthrough innovation
in small blood vessels grafting
Executive summary

3. Gabriele
Grecchi
Fund raising &
business development
MBA at INSEAD
Antonio
Alessandrino
Technology & product development
Ph. D. in Materials Engineering
at Politecnico di Milano
Lorenzo
Sala
Process & operations
Master Degree in
Management Engineering at
Politecnico di Milano
Our team

4. Giuliano
Freddi
Head of Biotech and
Biomaterials Dept. at
Innovhub Stazioni
Sperimentali per l’Industria
Prof. Piergiorgio
Settembrini
Director at the Cardiovascular
Specialization School at
Università di Milano
Business
advisors
Project Managers &
Business Developer at
some medtech companies
Our advisors

5. The unmet clinical need
The use of autografts is limited due to the lack of tissue donors, previous harvesting or anatomical variability,
whereas xenografts and allografts suffer from their relatively shorter life span and might be rejected by the
immune system. Finally, synthetic prosthetic grafts fails because of stenoses, thromboses or chronic inflammation
What is the problem?
Each year, 1.4m patients in the US need arterial prostheses. The available
options for the replacement of vascular grafts have limited clinical success,
with a cost of more than $25 billion because of hospital readmissions
The golden standard for these transplants is autologous grafts
Alternatives to autografts - such as allografts, xenografts, artificial
prostheses or synthetic vascular grafts - still have important limits

6. Tissue engineering is an alternative approach for
creating new vascular grafts
SilkByPass combines the biomimetic properties
of nano-fibrous electrospun silk fibroin with the
mechanical advantages of micro-fibrous silk fabrics
Our technology stimulates fast
natural* human tissue regeneration
Physiological post-surgery
body reaction occurs in situ**
No rejection risks, easy surgery, no
dangerous degradation products
Our solutions
* without cells, drugs or growth factors. Tissue regeneration is faster than fibroin degradation
** site-specific tissue regeneration

7. The market
The TEVGs opportunity
SilkBiomaterials will initially address
Tissue Engineered Vascular Grafts in
the CABG market
2.7m/yr coronary revascularisation
procedures in OECD countries, of
which 560k/yr CABG surgeries
No true successful TEVG on the
market, yet.
SilkByPass’ disruptive technology
could command a premium price
$9.7Bn/yr CABG
market in
OECD countries*$90Bn market for
tissue engineering
in 2016
+20% CAGR (’12-’18) in
cardiology & vascular
$4.1Bn
TEVG
addressable
market**
* the estimated price of a coronary bypass surgery on average across 24 OECD countries was about USD 17’400 in 2011
** based on an average 3.3 grafts per procedure and an ASP $1’580/graft, as estimated via interviews and market research

8. Benefits Autografts SilkByPass
Allografts &
Xenografts
Synthetic grafts
Device availability
No calcification
No harvesting
No drug treatments
No rejection
Physiological body reaction
No dangerous degradation products
No fibrotic tissues
Our clear advantages

9. Competitor analysis
patency rate
W. L. Gore & Associates, Inc.
Propaten vascular grafts (knitted Gore-tex functionalized with heparin bonded on the lumen
surface of the grafts): 28% of sever adverse events; loss of patency in 30% of patients within 12
months. Literature and interviewed surgeons agree in define in 24 months the expected working-
life of Propaten vascular graft
B. Braun Melsungen AG
Uni-Graft (impregnated polyester) and Vascular Graft PTFE (knitted PTFE): both grafts are related
to thrombosis, loss of patency, scar tissue leading to the failure of the grafts within two years
Le Maitre Vascular Inc.
Lifespan (PTFE): time of occlusion lower than 180 days
Omniflow II biosynthetic vascular graft (cross-linked ovine collagen with a polyester mesh
endoskeleton): loss patency in about 50% of patients within 9 months
Cryolife
ProCol Vascular Bioprosthesis (bovine vein processed with gluaraldehyde): occurrence of
thrombosis of 70% and a patency rate of 36% after 12 months
Cytograft Tissue Enginnering Inc.
Autologous cell sheet based grafts assembled in a tubular shape (Lifeline): strong law
requirements; very long manufacturing time of a single graft (up to 9 months); pricing around
$15’000-$25’000. Patency rate of 60% after 6 months (Preliminary clinical study)
SilkBiomaterials S.r.l.
SilkByPass stimulates the regeneration of functional small blood vessel tissues and it has so far
reached compliance similar to those of saphenous vein
No biological issue in production, manufacturing easy as a synthetic, tissue regeneration better
than a biological
functionaltissueregeneration
Lifeline
SilkByPass
ProCol
Omniflow
Propaten
Lifespan
Uni-Graf

10. A unique patented* technology
which represents a breakthrough
innovation in the manufacturing
of silk fibroin tissue engineered
medical devices
Surgeons would be able to use
an easy to sterilize, store and
implant vascularization
medical device
SilkByPass is made of
fibroin, an already FDA-
approved material
Our best features
* filed on 27/10/2014, submission #MI2014A001841

11. Progress so far
Electro-spinning ComplianceBurst
Generated the
nano-fibrous matrix
In vivo tests
Prototype
Verified the burst pressure
of the nano-fibrous part
Simulated the small
blood vessel compliance
vs. saphenous vein et al.
Implanted the nano-
fibrous part into rats
(abdominal aorta)
Already designed the first
SilkByPass scaffold
Nano & micro
combination
See appendix for additional references
Strength Biological validation
Good mechanical
properties
Performed site specific
biological validation
Manufacturing
Generated the
micro-fibrous matrix

12. CE Mark project timeline
Lab tests
Preliminary
biological tests
Biological validation
ISO 10993
First human
clinical trials
Funding needs
1H15 2H15 1H16 2H16 2017 2020
€ 500.000 € 6.500.000

13. Go-to-market strategy
European roll-out, then
US post-FDA approval
Direct sales
Prove clinical viability &
physician/patient satisfaction
Acquirers
Target hospitals in the
acquirers’ sales channels
Lean sales strategy
On top of safety and efficacy,
develop parallel cost engineering
Focus on costs
After the CE mark regulatory approval, SilkByPass should be sold directly
to hospitals, allowing for an educational component to train physicians
Medical device acquirers pay for proof of penetration or KOL
uptake. We should target hospitals where their KOLs operate
A small team (4/5 sales reps + 2/3 clinical specialists) should execute
a focused and targeted rollout, building clinical experience
Our key customers are medical device companies: they are
interested in high margin products, not big sales teams

14. Seed round and use of proceeds
First application and
maintenance fees
R&D G&A
PersonnelPatents
Preliminary biological
& animal tests
Travel, advisory & legal,
office rent and marketing
Production specialist
& researchers
25%
45%
8%
22%
€500k

15. Recent achievements
We are building momentum and looking for non-dilutive sources of funding and external support
Accelerator Finalist
€ 25’000 in services
1st prize winner
€ 50’000 in services
1st absolute winner
€ 30’000 grant
Selection winner
$ 100’000 convertible

16. Help us disrupt
the tissue engineering ecosystem

17. silkbiomaterials.com
contact@silkbiomaterials.com
twitter.com/SilkBioMat
Contact details

18. Technical appendix

19. This is part of our technology
A bit of nano-fibrous silk
We perform a procedure called
“electrospinning” of silk fibroin 2D
matrices V
+
Injection
system
Collector
Spinneret
FiberDistance
Nanofiber
Polymeric jet
Polymeric solution
Collector
High voltage
generators

20. An ingredient of our technology
…and sub-micrometric fibersWe get uniform…

21. Cell compatibility
0
10
20
30
40
50
60
70
80
90
100
1 3 7
%Reduced
days
ES film
control
Murine fibroblasts (L929 - 7x105 cell/ml)
Cell viability similar to control
Decrease at 7 days -> cell confluence
Cell interaction Test -
Alamar blue Test

22. Cell interaction Test – SEM1day7days
3days7days(backside)
AdhesionandproliferationCellsconfluence
PartiallycolonizedmatrixCellsthoughthematrix

23. Electro-spinning of tubular matrices
V
+
ω"

24. Our first test with blood vessels
In-vivo test with rats
Abdominal aorta
1,5mm Ø

25. Scaffold integrated by the new tissue
a-b) t=0; the nanofibrous matrix is
implanted without drugs, cells and
growth factors
c-d-e-f) t=7 days; the matrix after 7 days
is completed integrated in functional
vascular tissue

26. Amazing results
1. Cellular intimal layer similar to the natural tunica intima
2. Vasa vasorum (D,E: black arrows)
3. Cells in all the thickness

27. Amazing results
Organized elastic lamina

28. Amazing results
• muscle cells (α-actin) (A): layer
similar to the tunica media of native
arteries
• elastic fibers (elastin) (C):
corrugated elastic lamina layer
adjacent to the vessel lumen
• endothelial cells (vWF) (E):
monolayer covering the lumen of
the grafts

29. 2
Amazing results
Macrophages: YES (red)
T-lymphocytes: NO
Physiological
inflammatory response
NO attack from the
immune system
1
3

30. A bit of micro-fibrous silk:
we have micro-fibrous
tubular textile matrices
Another component of our technology

31. maximumtensilestrength(N)
400
800
1.200
1.600
sample 1 sample 2 sample 3 sample 4 sample 5
High range of possible
mechanical properties
Mechanical properties

32. Cells are able to adhere and
colonize the micro-fibrous
textile silk fibroin matrix
Murine fibroblast (L929)
1 day
7 days
Cells interaction tests - SEM

33. Also site specific cells
Primary muscular cells from
pig aorta
7 days
7 days
Cells interaction tests - histologies