Manel Cascallo / VCN Biosciences open innovation case

How tech transfer experiences lead to a biotech foundation:

VCN Biosciences case-report April 10th, 2014

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


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)


Genesis of VCN Biosciences

Virotherapy Group at ICO / IDIBELL experience

2001 2002 2003 2007 2004 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.


Dr. Ramon Alemany Dr. Manel Cascalló Dr. 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

About VCN Biosciences

Mission & View


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).


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



Mission & View


BUSINESS MODELS in BIOTECH sector

HIGH Investment Medium

© Nature Group

Building up VCN Biosciences


The three pillars of a biotech company:

TECHNOLOGY MANAGEMENT INVESTMENT



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 OPPORTUNITIESMANAGEMENT

ORGANIZATION

TRAINING

& CONSULTING

FUNDING

SEARCH

GROWTH

STRATEGY



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

VC

N-0

1

Regulatory Preclinics

PRECLINICS VCN-02 Clinical Phase 1

VCN-02

VC

N-0

2

Regulatory

VCN-02

PRECLINICS

VCN-03 VC

N-0

3

Regulatory

VCN-03

Phase 1

VCN-03



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

Vir

us

in b

loo

d

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

% tu

mo

r g

row

th v

s d

ay 0

VCN-01

% tu

mo

r g

row

th v

s d

ay 0

VCN-01

3.- Antitumoral ACTIVITY



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

Vo

lum

e (m

m3 )

day pi

Tumor volume NP-9(Mean ± S.E.)

PBSVCN01

Hyaluronic Acid (HA) staining

Digested HA(neg. ctrl)

vehicleVCN01

(day 79 p.i.)

hyaluronic acid hyaluronic acid

Intravenous

Administration

*, p<0.05 vs vehicle group



Preclinical Package: Pharmacology of VCN-01 ± Gemcitabine

day 0 day 80

nude

MICEday -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

Hamsterday -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

ᵟ P<0.01 vs VCN-01

P<0.01 vs PBS*



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


UI/

l

Day 8

vehicle

VCN-01 at 2,5E11 vp

VCN-01 at 4E11 vp

1

10

100

1000

10000

100000


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

x10

E6 c

ells

/mL

Day 2

0,001

0,01

0,1

1

10

100

male female male female male female male female male female

x10

E6 c

ells

/mL

Day 8

vehicle

VCN-01 at 2,5E11 vp

VCN-01 at 4E11 vp

Lymphocytes Neutrophils Eosinophils Basophils Monocytes

Lymphocytes Neutrophils Eosinophils Basophils Monocytes

**

*

*

1

10

100

1000

10000

100000

male female male femaleU

I/l

Day 8

vehicle

VCN-01 at 2,5E11 vp

VCN-01 at 4E11 vp

* p <0.05 vs vehicle group

Mice

Hamster

Day 12 Day 7



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%



Gabriel Capellà (4,4 %)



New Investor (40%)

Second Round Grifols

(expected)






New Investor (40%)

CO

MP

AN

Y V

AL

UE






New Investor (40%)



MANAGEMENT

ORGANIZATION

TRAINING

& CONSULTING

FUNDING

SEARCH

GROWTH

STRATEGYFounder 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. Amat Dr. Cascalló


VCN Biosciences Pipeline

Proof of

concept Phase II

Candidate

definition Phase I

Regulatory

Preclínics

Hyaluronidase

Technology

VCN-01

T1- Technology Out-licensed to

ORCA Therapeutics BV

VCN-02

Technology

VCN-02

Pre-candidates

VCN Technologies



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


Thank you!


Dr. Manel Cascalló

Chief Executive Officer

VCN Biosciences SL


Av de la Generalitat 152

08174 - Sant Cugat del Vallès (Barcelona, SPAIN)

phone: +34 571 2359 / + 34 609432375

[email protected]

Funding:

- NEBT2010 - ACC10

- Programa INNPACTO-2012

- CDTI – PiD 2013

http://www.vcnbiosciences.com/

tel:%2B 34 609432375

mailto:[email protected]

Manel Cascallo / VCN Biosciences open innovation case

Healthcare

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