Presentation given by Manel Cascallo, from VCN Biosciences, in the framework of the Emergence Forum Barcelona Biocat organized the Barcelona Emergence Forum (April 10-11th, 2014, Congress Palace, Montjuïc) supported by the TRANSBIO SUDOE, a translational cooperation project dedicated to innovation in life sciences in South-West Europe. The Barcelona Emergence Forum contributed to bringing together Academics, Companies, Investment Entities, Technology Platforms and Technology Transfer Offices from Spain, France and Portugal to set up collaborative projects on Human Health & Agro-food Innovation. More information at: http://www.b2match.eu/emergenceforum2014

1. How tech transfer experiences lead to a biotech foundation:
VCN Biosciences case-report
April 10th, 2014

2. www.vcnbiosciences.com
The origin
Virotherapy Group at ICO / IDIBELL: The team
Name: Cancer Virotherapy
Created: 2001
Group Leader: Dr. Ramon Alemany
IP’s: Ramon Alemany / Manel Cascalló

3. www.vcnbiosciences.com
The origin
normal cell:
abortive replication
Productive
replication
Mechanism of Action
Spread to neighbouring cells
Selective killing of
tumour cells
Self-amplification effect
Potential stimulation of
an antitumoral immune
response
Oncolytic Virotherapy =
Use of replication competent viruses to
selectively destroy cancer cells
Technology
(Extracted from Hedley et al. 2006)

4. www.vcnbiosciences.com
Genesis of VCN Biosciences
Virotherapy Group at ICO / IDIBELL experience
2001 2002 2003 20072004 2005 2006 2008 2009 2010
1rst patent
(VA technology)
2nd patent
(DM technology)
3rd patent
(T1 tech.)
Technology Acquisition
by ORCA Therapeutics
(Holland)
EUREKA project
VCN creation
Regulatory Phase
with ICOVIR-5
Approval by:
- AEMPS
- Environmental Ministry
- Clinical committee at
Hospitals
4th patent
(hyal. tech.)
Technology Transfer to
DNAtrix (USA)
Compassionate Use
Assays ICOVIR-5
Technology Acquisition
by Oncolytics BioTech
(Canada)
CONTRACT RESEARCH
with Oncolytics BioTech.

5. www.vcnbiosciences.com
Dr. Ramon Alemany Dr. Manel CascallóDr. Gabriel Capellà
Internationally Recognized Scientifics
Expertise in Clinical Development of Oncolytic viruses
Inventors of >5 patents & Company Consultants
Business Management Expertise
ENTERPRENEUR TEAM
adhoc Scientific Advisory Board
Dr. Jose Costa (Yale Univ., USA)
Dr. Nick Lemoine (QMCR, UK)
Dr. Ramon Salazar (ICO, Spain)
Dr. Manuel Hidalgo (CNIO, Spain)
Strategic Consultancy
BIOEMPREN SL
(Mr. Jaume Amat)
Hyaluronidase Tech. Transfer
IDIBELL / ICO
Commercial agreement with
a CMO for viral batch production
GenIBET
(Portugal)
Genesis of VCN Biosciences
The decision

6. About VCN Biosciences
Mission & View
www.vcnbiosciences.com
VCN Biosciences was created in 2009 with the aim of developing new agents for the treatment of cancer using a
technological platform based on oncolytic adenoviruses.
VCN Biosciences mission is the development of new candidate oncolytic adenoviruses from its design and
preclinical studies to the validation of their antitumoural efficacy in human patients (Phase I and II clinical trials).

7. www.vcnbiosciences.com
Rational Design of a Clinical candidate
HAd5
(wild-type)
Clinical candidate
selectivity of replication
in tumour cells
Tumour potency
(diffusion)
biodistribution selectivity
(tumour targeting)
Mechanism of Action
Selective killing of tumor cells by effect of its
replication, which results in a self-
amplification of the initial inoculum that is
released after cell lysis and spread through
the tumor mass
The expression of a secreted soluble
hyaluronidase, which degrades partially the
extracellular matrix of the tumor facilitating the
diffusion of the virus progeny and increasing
the accessibility for chemotherapy
About VCN Biosciences

8. About VCN Biosciences
Mission & View
www.vcnbiosciences.com
BUSINESS MODELS in BIOTECH sector
HIGHInvestment Medium
© Nature Group

9. Building up VCN Biosciences
www.vcnbiosciences.com
The three pillars of a biotech company:
TECHNOLOGY MANAGEMENT INVESTMENT

10. Building up VCN Biosciences
www.vcnbiosciences.com
INTELLECTUAL PROPERTY
- Prosecution of patents
- IP strategy
TECHNOLOGY MANAGEMENT
CANDIDATE DEVELOPMENT
- Preclinical package
- Manufacturing
- Clinical Program
- Regulatory Validation
PORTFOLIO CREATION
- New technologies
- Portfolio strategy
MANAGEMENT INVESTMENT
BUDGET STRUCTURE
ACTIVITY SCHEDULING
FINANCIAL OPPORTUNITIES
MANAGEMENT
ORGANIZATION
TRAINING
& CONSULTING
FUNDING
SEARCH
GROWTH
STRATEGY

11. Building up VCN Biosciences
www.vcnbiosciences.com
INTELLECTUAL PROPERTY
- Prosecution of patents
- IP strategy
TECHNOLOGY MANAGEMENT
CANDIDATE DEVELOPMENT
- Preclinical package
- Manufacturing
- Clinical Program
- Regulatory Validation
PORTFOLIO CREATION
- New technologies
- Portfolio strategy
2019
Clinical Phase 2
i.v Pancreas
Clinical Phase 2
Other tumor target ?
2010 2011 2012 2016
Preclinics +
Manufacturing
2013 2014 2015 2017
Clinical Phase 1
intratumoral
Clinical Phase 1
intravenous
2018
VCN-01
Regulatory Preclinics
PRECLINICS VCN-02
Clinical Phase 1
VCN-02
VCN-02
Regulatory
VCN-02
PRECLINICS
VCN-03
VCN-03
Regulatory
VCN-03
Phase 1
VCN-03

12. Building up VCN Biosciences
www.vcnbiosciences.com
1.- Biodistribution
Liver
PBS Wild-type
capsid
RGDK
capsid
1,00E+04
1,00E+05
1,00E+06
1,00E+07
1,00E+08
1,00E+09
1,00E+10
0 500 1000 1500 2000
Virusinblood
Time (minutes)
ICO17
VCN01
2.- Pharmacokinetics
Orphan Drug Designation for the
Treatment of Pancreatic Cancer
Decision adopted by EMA
on June 21th, 2011
(EU/3/11/880 - EMA/OD/008/11)
Days post-injection
%tumorgrowthvsday0
VCN-01
%tumorgrowthvsday0
VCN-01
3.- Antitumoral ACTIVITY

13. Building up VCN Biosciences
www.vcnbiosciences.com
Preclinical Package: Pharmacology of VCN-01
Intratumoral
Administration
*p<0.05 vs PBS
# p<0.05 vs VCN-01 (4xE9vp)
0
500
1000
1500
2000
2500
-1 19 39 59 79
Volume(mm3)
day pi
Tumor volume NP-9
(Mean ± S.E.)
PBS
VCN01
Hyaluronic Acid (HA)
staining
Digested HA
(neg. ctrl)
vehicle
VCN01
(day79 p.i.)
hyaluronic acid hyaluronic acid
Intravenous
Administration
*, p<0.05 vs vehicle group

14. Building up VCN Biosciences
www.vcnbiosciences.com
Preclinical Package: Pharmacology of VCN-01 ± Gemcitabine
day 0 day 80
nude
MICE
day -15
Tumor cells
- VCN-01 i.v. at 5.1010 vp (1X): day 0
- GE i.p. at 100 mg/kg (3X): day 0,2,4,6
Human xenograft model
in mice
Syngenic Model in Syrian
Hamster
day 0 day 45
Syrian
Hamster
day -15
Tumor cells
GE i.p. at 50 mg/kg (7X): day 0,3,6,9,12,15,18)
VCN-01 i.t. at 25.1010 vp (1X): day 0, 9 & 18)
# P<0.01 vs GE
ᵟP<0.01 vs VCN-01
P<0.01 vs PBS
*

15. Building up VCN Biosciences
www.vcnbiosciences.com
Preclinical Package: Toxicity profile
* p<0.05 vs PBS
Transaminases
1
10
100
1000
10000
100000
male female male female
UI/l
Day 2
1
10
100
1000
10000
100000
male female male female
UI/l
Day 8
vehicle
VCN-01 at 2,5E11 vp
VCN-01 at 4E11 vp
1
10
100
1000
10000
100000
male female male female
UI/l
Day 28
AST ALT AST ALT AST ALT
*p <0.05 vs vehicle group
*
*
Total white blood cells count
0,001
0,01
0,1
1
10
100
male female male female male female male female male female
x10E6cells/mL
Day 2
0,001
0,01
0,1
1
10
100
male female male female male female male female male female
x10E6cells/mL
Day 8
vehicl
VCN-0
VCN-0
Lymphocytes Neutrophils Eosinophils Basophils Monocytes
Lymphocytes Neutrophils Eosinophils Basophils Monocytes
*
*
*
*
1
10
100
1000
10000
100000
male female male female
UI/l
Day 8
vehicle
VCN-01 at 2,5E11 vp
VCN-01 at 4E11 vp
*p <0.05 vs vehicle group
Mice
Hamster
Day 12Day 7

16. Building up VCN Biosciences
www.vcnbiosciences.com
MANAGEMENT INVESTMENT
BUDGET STRUCTURE
ACTIVITY SCHEDULING
FINANCIAL OPPORTUNITIES
FFF
entrance
Manel Cascalló (59,13 %)
Ramon Alemany (7,39%)
Gabriel Capellà (7,39%)
BIOVCN Patrimonial (13,66 %)
BIOCAPE Grup (12,43 %)
Founders: 100%
Manel Cascalló (35,5 %)
Ramon Alemany (4,4%)
Gabriel Capellà (4,4 %)
BIOVCN Patrimonial (8,2 %)
BIOCAPE Grup (7,5 %)
New Investor (40%)
Second Round Grifols
(expected)
Manel Cascalló (35,5 %)
Ramon Alemany (4,4%)
Gabriel Capellà (4,4 %)
BIOVCN Patrimonial (8,2 %)
BIOCAPE Grup (7,5 %)
New Investor (40%)
COMPANYVALUE
Manel Cascalló (35,5 %)
Ramon Alemany (4,4%)
Gabriel Capellà (4,4 %)
BIOVCN Patrimonial (8,2 %)
BIOCAPE Grup (7,5 %)
New Investor (40%)

17. Building up VCN Biosciences
www.vcnbiosciences.com
MANAGEMENT
ORGANIZATION
TRAINING
& CONSULTING
FUNDING
SEARCH
GROWTH
STRATEGY
Founder Team
Dr. Alemany
Virotherapy Expert
Dr . Capellà
Cancer Genetics
Expert
Contract Research
with academia
Scientific Advisory Committe
Dr. Hidalgo
CNIO
Dr. Salazar
ICO
Dr. Costa
Yale Univ.
Dr. Cascallo,
CEO / Founder
Ms. Viaplana
Clinical Research
Manager
Ms. Blasi
Regulatory
Affairs
Manager
Dr. Bazan
R&D Manager
Clinical
Commitee
Scientists
Team
Board of Directors
Dr. Terencio Dr. Büscher Dr. Costa Mr. AmatDr. Cascalló

18. www.vcnbiosciences.com
VCN Biosciences Pipeline
Proof of
concept
Phase II
Candidate
definition
Phase I
Regulatory
Preclínics
Hyaluronidase
Technology
VCN-01
T1- Technology
Out-licensed to
ORCATherapeutics BV
VCN-02
Technology
VCN-02
Pre-candidates
VCN Technologies
Building up VCN Biosciences

19. www.vcnbiosciences.com
Clinical program with VCN-01
Phase I by Intravenous
Administration ±GE
(EudraCT number: 2012-005555-16 )
Phase I by Intratumoral
Administration ±GE
(EudraCT number: 2012-005556-42 )
Study Type Open-label / Dose Escalation Open-label / Dose Escalation
Dosage Range 1xE11 vp to 1xE13 vp/patient
(6 dose levels)
1xE10 vp to 1xE12 vp/tumor
(5 dose levels)
Administration Continuous infusion EUS guided
Number of patients 24 to 33 20 to 27
Clinical Sites 1. Institut Català d’Oncologia
(BCN)
2. Centro Integral Oncológico Clara
Campal (Madrid)
1. Institut Català d’Oncologia
(BCN) / Hospital Bellvitge
2.Centro Integral Oncológico
Clara Campal (Madrid)
Starting Date January 2014 January 2014
Estimative Duration Enrollment 24 months 19 months
Building up VCN Biosciences

20. Thank you!
www.vcnbiosciences.com
Dr. Manel Cascalló
Chief Executive Officer
VCN Biosciences SL
www.vcnbiosciences.com
Av de la Generalitat 152
08174 - Sant Cugat del Vallès (Barcelona, SPAIN)
phone: +34 571 2359 / + 34 609432375
mcascallo@vcnbiosciences.com
Funding:
- NEBT2010 - ACC10
- Programa INNPACTO-2012
- CDTI – PiD 2013