from fundamental research to structured technology transfer – the vub model prof. jan cornelis...

From fundamental research to structured technology transfer – the VUB model

Prof. Jan Cornelis

Vicerector Research

Dubrovnik-UNICA 2008| pag. 2

Presentation outline

IP ownership regulation in 1991 and now

Fundamental research in the Lab of Raymond Hamers leads to a break-through technology

What did we learn?

Where VUB stands today in technology and knowledge management


Bayh-Dole act in US Situation in Belgium (Flanders)

Bayh-Dole Act of 1980 requires U.S. universities to put into use the intellectual property rights generated from their federally funded research

No equivalent in Belgium / Flanders until 1998


Presentation outline

IP ownership regulation in 1991 and now

Fundamental research in the Lab of Raymond Hamers leads to a break-through technology

What did we learn?

Where VUB stands today in technology and knowledge management


1991: getting the environment right

VUB professor Raymond Hamers and the “wild west” of biotechnology

Generator of diversity...

Fundamental Research:Molecular immunology

DNA-protein interactions: antibodies against DNA

Parasitology: sleeping disease, malaria…cloning and cristallisation of antibodies against carbohydrates (very important in the interaction processes between cells)

-> ?monoclonal antibodies, but this seemed impossible in practice


Our attitude in fundamental research

No thematic steering – initiative of individuals and research groups

Internal quality control based on peers and correlated with bibliometry

Depth of the project reviewing process depending on the level of research:

- Seed level: quality of proposal; starters investement- Incubation level: matching of externally acquired

funds- Excellence level: external peer review


The students !

Student ‘practicum’ immunology: ? blood of the teaching assistant to isolate antibodies

-> ‘80s: students refuse out of fear for hiv contamination

? collect blood from a mouse-> experiment already done several times, no useless

killing

The research group ‘sleeping disease’ received blood samples from camels from Mali:

use of some camel blood for the experiment


Investment in talent & technology

Investment in new talent – important motivation of R&D

Research in university context ensures crossfertilisation education/research


The discovery !

Results: not as expected•possible reasons:

•the students have done something wrong•there’s something wrong with the blood samples •there’s something else going on

•possible solution: •ignore these results conduct further research on fresh camel blood

•the results:

cameloïds posses a different kind of antibodies


What they found: nanobodies®

Fv

VHH

single domain antigen binding fragment (15 kDa)NANOBODY®

CH1 VHCLVL

CH3

CH2

Fc conventional antibody

VHH

CH2

CH3

Fc

camel heavy-chain antibody

Hamers et al., Nature, 1993


Spotting the value

Laboratory: : constant shortage of cash

Not yet in an era where ‘publications’ were an absolute must for researchers

Seeing the possibilities of the camel antibodies:

file a patent, before publication!


Patent and publication

‘Hamers1’ patent was filed(Hamers, Casterman)Immunoglobulins devoid of light chains (priority date 21/8/1992)

Publication in Nature. 1993 Jun 3;363(6428):446-8

Luckily, in this order !


Patent portfolio: valorisation @ vub

Patent costs soon became considerable: inventors turned to the VUB

• 21/8/1992 ep19920402326 immunoglobulins devoid of light chains• 29/4/1993 ep19930201239 production of antibodies or (functionalized) fragments

thereof derived from heavy chain immunoglobulins of camelidae • 2/8/1993: fr19930009511 recombinant vector containing a lipoprotein gene sequence

for expressing nucleotide sequences • 25/4/1995: ep19950400932 variable fragments of immunoglobulins - use for

therapeutic or veterinary purposes + ......

Agreement on transfer of the patent to the VUB (1995): no framework or ruling existed regarding IP a deal was set up to distribute possible income from

the patents


Opportunity vs risk

The university was unexperienced• no specialised technology transfer cell

The researchers were unexperienced• starting negotiations without a non-disclosure

agreement• company starts filing patents around the nanobody

technology

-> licence-agreement VUB - Unilever (1997) on ‘non-healthcare’ applications


Flemish Institute of Biotechnology

Start of the VIB (VlaamsInstituut Biotechnologie): 1997

www.vib.be

Raymond Hamers’ lab becomes a VIB-department

Agreement VUB-VIB• VIB takes the lead in commercialisation• Income distribution system

16

VIB-Virtual research institute

• Virtual institutes, cherishing the best talents without fragmentizing or duplicating efforts and investments

• Advantages

• - light weight central administration dedicated to specific R&D theme

• - research is done by university partners, residing in their local labs talent creation for the sector

• - the best from each research domain are involved• • - bridging gaps between different monodisciplinary research domains

• - balanced/mixed leadership between industry and university

• - Coherence of action

• - Very high R&D performance

Dangers

• - Unique entry point for all R&D rules for new entries and exits of research groups

• - Balance between internal competition and collaboration


Creation in 2001 of the spin-off Ablynx

• Licence to Ablynx: diagnostics & therapeutics• 5 mio € capital

www.Ablynx.com

• External CEO (Mark Vaeck) + 4 researchers VIB/VUB• Start of several government-funded research projects

with VUB/ VIB department• Ablynx becomes a biopharmaceutical company that

further develops the Nanobody ® Technology


Company history and milestones

2001

Ablynx established by VIB and GIMV

Mark Vaeck joins as CEO

Grant by VIB of rights to the Nanobody technology and patent portfolio for all human and animal healthcare applications

€2mm seed money

2002 2003 2004 2005 2006 2007

Began research operations

€3mm from Sofinnova and Gilde

Hennie Hoogenboom joins as CSO

Collaboration with Novartis

Collaboration with P&GP

Raised €25mm from Alta Partners and existing shareholders

Edwin Moses joins as Chairman of the Board

Achieved first milestone and extended scope of P&GP collaboration

Edwin Moses becomes CEO, Wim Ottevaere joins as CFO, Eva-Lotta Allan joins as CBO

Raised €40mm from KBC Private Equity, SROne and existing shareholders

Collaboration with Wyeth—$212.5mm licensing agreement on TNFα

Moved into new facilities (Ghent)

First clinical trial of Nanobody (ALX-0081)

€206mm collaborative agreement with Boehringer Ingelheim for AD

Josefin-Beate Holz joins as CMO Awarded €1.9mm grant to develop new

therapeutic applications of Nanobodies €1.3bn collaborative agreement with

Boehringer Ingelheim


Ablynx history

Currently over 160 employees

Successful IPO on Euronext Brussels (ABLX) Nov 7th 2007

Extensive and actively managed IP portfolio: over 200 patent applications and patents in more than 50 patent families worldwide

Active protection of know-how and trade secrets

Trademarks: nanobody™ and nanoclone™


Ablynx business model

• internal programs focused primarily on clinically validated targets

• target selection based on commercial opportunity, nanobody competitive advantage and freedom to operate

• opportunistic therapeutic area focus

• Collaborate selectively on the development and

commercialization of certain Nanobodies

• Provide exclusivity on targets rather than

indications or therapeutic area

Pipeline development strategy

Partnering strategy


Established partnerships with industry leaders

Partnering rationale: External validation of the technology platform

Deal value: Not disclosed. R&D funding, R&D milestones and royalties

Type: Worldwide research and development agreement

Field: Targets in musculoskeletal indications and all other human therapeutics

Ablynx product rights: None retained

Year: 2004 & 2006

Partnering rationale: External validation and evaluation of platform across a range of targets

Deal value: Not disclosed. Deal includes up-front payments, R&D payments, license fees, milestones and royalties.

Type: Collaborative research program, exclusive license agreement on a target-by-target basis

Field: Multi-target


Year: 2005

Partnering rationale: Specialist in Alzheimer’s disease, strong biological manufacturing expertise

Deal value: €206 million (excluding royalties). Upfront, development and commercial milestones, FTE funding and royalties

Type: Worldwide research and licensing agreement

Field: Target in Alzheimer’s disease and all other human therapeutics


Year: 1H 2007

Partnering rationale: Partner has specific TNFα expertise (Enbrel®), and broad therapeutic area expertise.

Deal value: $212.5 million (excluding royalties) Upfront, development and commercial milestones, FTE funding and royalties

Type: Worldwide licensing agreement

Field: Exclusive rights to TNFα

Nanobodies for all human therapeutics


Year: 2006

Partnering rationale: Exploit the platform’s full capabilities across multiple therapeutic areas (restricted to just 10 different Nanobody therapeutics)

Deal value: €1.3bn; €75mm during the research term. Development milestones of €125mm per therapeutic program, and royalties

Type: Worldwide research and licensing agreement

Field: Human therapeutics

Ablynx product rights: Certain European co-promotion rights

Year: 2H 2007


The learning process...

Learning curve – for the university– for the scientists ....

... has lead to a valorization policy at the university, a regulation comprising IP management and income distributionand ... professionalization of thetechnology transfer interface cell


Knowledge management Technology transfer Interface

Multidisciplinairy team

(3FTE in 1999 -> 10 FTE + 4 consultants today)

Legal support contract research

Patent management & info-source (Patlib)

IP and contract managment

Creation of an entrepreneurial spirit (researchers, students...)

Spin-off creation

BI3 Fund (seed capital fund)

Research parks

Incubators IICB– ICAB

Industrial Network- Crosstalks


Patent portfolio of theVrije Universiteit Brusselwww.vub.ac.be

> 50 patent families (application) VUB

> 20 patent families (application) with IMEC

(Interuniversity institute for Micro-electronics)

> 10 patent families (application) with VIB

(Flemish Interuniversity institute Biotechnology)

•Several patent families (application) with

other research institutions and industry

More information on technology offers: www.vub.ac.be/valorisatie or contact [email protected]


Output indicators

Patents per FTE-professor: VUB ranks 3rd in Flanders

0

0.05

0.1

0.15

0.2

0.25

KUL UH UA UG VUB

IOF

para

mete

r 5 (

2001-2

005)

/ # V

TE

ZA

P 2

005


BI3 FundBI3 FundImagination- Incubation- Innovation

Aim: Provide seed capital for VUB spin-off companies

Partners: Fortis Private Equity, KBC Private Equity, Ethias Leven, GIMB, VUB

Value: 6 mio Euro (extendable to 12 mio Euro)

Obtained in 2006 VINNOF recognition

Participations: Elsyca, BruCells, Symbion, Eggcentris


21 spin-offs21 spin-offs of theVrije Universiteit Brussel


Output indicators

Spin-offs per FTE-professor: VUB ranks 1st in Flanders

0

0.005

0.01

0.015

0.02

0.025

0.03

KUL UH UA UG VUB

aan

tal o

pg

eri

ch

te s

pin

-off

s (

2001-2

005)

/ # V

TE

ZA

P in

2005


Incubators of the Vrije Universiteit BrusselIncubators of the Vrije Universiteit Brussel

Brussels: ICAB

Incubator Arsenaal Brussel Near campus Etterbeek

Operational in 2008

Flanders: IICB

Innovation & Incubation center ZellikNear campus Jette

www.iicb.be

www.vub.ac.be


Partner for industry:

* Medium to long term research projects

* Contract research

* Consultancy and testing facilities

* Training & industrial residents

Contact the technology transfer interface

[email protected]

Research at of theVrije Universiteit Brusselwww.vub.ac.be


Crosstalksthe VUB industry- university network

Creating an exchange dynamicsEncouraging cross-talking and stimulating innovationThrough different formatsAnd international publications

Conferences, science & industry lunches, workshops...

•Windows by Day, Linux by Night: open source paradigma•The Future of Technology•The Future of our Digital Commons•Early Warning Signals•Grenzen van de Geneeskunst•Early Warning Information Systems •The Future of Medication in a Patient-Centered Health Care

•.........

http://crosstalks.vub.ac.be


Technological entrepreneurship education program

Introduce technological entrepreneurship in the Masters Engineer <-> Business engineer

Courses Business administration <-> Technology Entrepreneurship <-> Entrepreneurship

for Bus.engineers Writing of a business plan Start up of a student business via ETC (Entrepreneurial Talent Corporation)

Partners PMV, Yakult, Ethias, WTCM, IBM, Fundus, Bank De Groof, Solvay, Bekaert, Tyco Electronics Raychem,...

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are needed to see this picture.

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Sketchy Technology Life Cycle

Program driven Project driven

Embryonic Potentialgrowth

Growth Mature Aging

IndustrialIndustrial ProductProduct

Generic

technology

Joint research

Proprietary

from fundamental research to structured technology transfer – the vub model prof. jan cornelis...

Documents

fundamental research

level of research

funded research

experiment slide

practice slide

knowledge management

external peer review

fresh camel blood