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C2W Life Sciences: 19 April 2010
In tijden van crisis 12,5 miljoen binnenhalen voor een 1,5 jaar oude starter, kan alleen met een ijzersterk verhaal. ArGEN-X belooft snel en simpel krachtige menselijke antilichamen te maken. ‘Zonder subsidies kom je er als biotechstarter niet.’“Het zal niet lang meer duren voordat wij mee kunnen spelen in de grote wereld van de farma”, stelt Tim Van Hauwermeiren, ceo van de Vlaams-Nederlandse start-up arGEN-X. “Onze antibodysysteem SIMPLE genereert met behulp van lama’s niet één goede lead antistof tegen een ziekte, maar een heel scala aan humane antilichamen. We kunnen kiezkeuriger zijn dan onze concurrenten en het allerbeste antilichaam eruit pikken. De techniek is zo simpel dat de tien nieuwe onderzoekers die we van geld uit onze laatste financieringsronde aannamen, hem binnen no time onder de knie hadden.”
ArGEN-X wordt geleid door een managementtrio dat zijn sporen in de antilichaamwereld al ruimschoots verdiende tijdens de opzet van Ablynx. Nadat dat was uitgegroeid tot een succesvol bedrijf met ruim 200 medewerkers, begon het ondernemersinstinct van de heren weer te kriebelen. Hans de Haard, chief scientific officer van arGEN-X en hoogleraar aan de Universiteit van Utrecht, voelde het als eerste. “Jaren geleden al werkte ik voor het eerst met humane antistoffen tijdens mijn post-doc aan de Universiteit van Maastricht, en bij mij overstap naar Unilever, keek ik een keer naar homologen in het dierenrijk. Ik probeerde in een opwelling met humane primers het DNA van conventionele antilichamen van kameelachtigen te vermenigvuldigen. Tot mijn grote verbazing lukte dat heel erg goed. De verschillen tussen humane antilichamen en die van kameelachtigen verschilden veel minder dan gedacht: op een paar aminozuren na waren ze identiek.”
Destijds was er geen interesse in die ontdekking. Maar in 2008 werd zijn Duitse ex-Ablynx-collega Torsten Dreier (chief development officer van arGEN-X) razend enthousiast. “Vanuit zijn ervaring met klinische ontwikkeling zag hij grootse mogelijkheden voor deze antilichamen als therapie. We vroegen Tim erbij en besloten weer het avontuur in te duiken.”
Chronische ziektes
Qua targets richt arGEN-X zich vooral op chronische ziekten. “Onze antilichamen zijn vrij groot en hebben een lachaam heeft al in muistesten bewezen dat het een veel effectiever ontstekingsremmer is dan alle concurrenge halfwaardetijd. Dan zijn deze ziekten een voor de hand liggend doel: uiteindelijk hopen we dat patiënten met een maandelijkse injectie geholpen kunnen worden, terwijl dit nu vaak om de paar dagen nodig is”, aldus De Haard. Zo ver is – arGEN-X, anderhalf jaar na oprichting, nog niet. Met die 12,5 miljoen hopen ze het komende jaar hun drie leadverzamelingen voor bloedkanker, solid tumor kanker en een auto-immuunziekte – welke houden we liever geheim- grondig te testen. “Ons eerste uitgeselecteerde antilirende middelen. Dat willen we ook laten zien voor de andere twee producten in de pijplijn. Als alles goed gaat, kunnen we over 2 à 3 jaar de eerste klinische tests doen.”Doorgefokte muizen
Van Hauwermeiren: “Wij zijn bij mijn weten het enige bedrijf dat met conventionele lama-antilichamen werkt. We hebben het ook uitgebreid gepatenteerd, van molecuul tot productie en selectie.”Om een serie leads te genereren, spuiten de wetenschappers van arGEN-X drie of vier lama’s in met een antigen. De dieren produceren een scala aan verschillende, zeer potente antilichamen tegen de lichaamsvreemde stof. Evolutionair staan ze vrij ver van de mens vandaan, dus roept inspuiting met bijvoorbeeld een menselijke cel een zeer heftige reactie op: ultrapotente antilichamen. Daarnaast hebben de lama’s een veel actiever immuunsysteem dan bijvoorbeeld labmuizen, omdat ze niet ingeteeld zijn. Via een bloedstaal worden de witte bloedlichaampjes uit de lama gehaald. “Dan heb je een hooiberg aan potentiële leads”, legt De Haard uit. “De truc is de juiste cellen te selecteren, die net dat variabele antibody stukje hebben dat zo effectief is. Hoe we die speld in de hooiberg vinden, houden we liever geheim.”
Na deze selectie halen ze het gen voor het goede antilichaam uit de cel en onderwerpen dat aan enige genetische modificatie. De lama antibodies verschillen maar 3 tot 5 aminozuren met de menselijke sequentie. Dat wordt aangepast en de onderzoekers plakken de menselijke varianten van de constante antilichaam-delen aan de sequentie. Dan is het een kwestie van in een CHO-cel transformeren en voila, je kunt zoveel puur menselijk antilichaam maken als je wilt.
“Een groot verschil met onze concurrenten als Regeneron en Medarex, is dat zij doorgefokte muizen gebruiken,” legt Van Hauwermeiren uit. “Dan genereer je veel minder diversiteit binnen je antilichaam populatie. Die diertjes verschillen nauwelijks nog van elkaar, waardoor ze ook weinig verschillende antilichamen produceren. Soms moeten ze wel honderd muizen immuniseren voordat ze een redelijke pool hebben. En dan is de affiniteit nog niet om over naar huis te schrijven.
De andere concurrenten zoals Dyax en Morphosys, gebruiken grote bibliotheken antilichamen. Dan heb je wel meer diversiteit, maar een zeer lage affiniteit. Met zware engineering moet die dan weer worden opgeschroefd, uiteindelijk heb je één goeie lead. Wij prikken een handvol lama’s voor tientallen antilichamen die divers zijn, een hoge affiniteit hebben en vrijwel identiek blijken aan de menseigen antilichamen. We hebben een veel sterkere uitgangspositie.”
De antilichaam-markt is met 40 miljard dollar en een groei van 20% per jaar één van de weinige farmaceutische takken die nog groter wordt. arGEN-X denkt vlug toe te treden tot de groten in dit veld. “De concurrentie wordt stelselmatig opgekocht, dus er is nog genoeg ruimte.”
Risicovolle Business
Hoewel het eerste werk voor arGEN-X aan de Universiteit Utrecht gebeurde, vertrok het bedrijf toch naar Vlaanderen. “We hebben de kansen eerlijk afgewogen en het Vlaamse klimaat is gewoon veel beter voor een starter in onze sector”, verklaart de Nederlander De Haard. “Het beste wat we in Nederland als subsidie konden krijgen was een dure lening! Deze business is zo risicovol, dat kun je nog zo’n sterk team hebben,zonder subsidies kom je er niet. In Vlaanderen zijn die mogelijkheden er wel, we kregen 1,3 miljoen euro als ‘zaaisubsidie’. Het VIB biedt enorme netwerkmogelijkheden en ondersteuning. In mijn ogen laat de Nederlandse overheid daar wel een steekje vallen. Er is genoeg wil en talent, maar als de overheid niet meewerkt vertrekken bedrijven toch. Ze zouden wat beter naar de buren moeten kijken.”Het VIB zag zelfs zoveel toekomst in arGEN-X, dat ze in de laatste ronde tot de investeerders zijn toegetreden. Een unicum, want het VIB investeerde tot nu toe alleen in zijn eigen starters. “We zijn er erg blij mee en zien het als een kwaliteitslabel”, aldus Van Hauwermeiren.
Dit artikel is eerder verschenen in C2W life sciences #7 2010. Auteur: Bo Blanckenburg
Articles
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Novel Platform Set to Transform Human Therapeutic Antibody Discovery & Development
Rotterdam, the Netherlands, July 8 2010 – arGEN-X, a biopharmaceutical company focused on the discovery and development of human monoclonal antibodies using its proprietary SIMPLE Antibody™ platform, announces that it has been granted the first patent covering the platform. The patent GB2461546B, has been granted by the UK Patent and Trademark Office (UKPTO).The broad granted patent covers arGEN-X’s SIMPLE Antibody™ technology, which yields gold standard human therapeutic antibodies with an unmatched functional diversity. It also covers arGEN-X’s antibody products as well as methods of generating them. arGEN-X is prosecuting additional patent applications globally, which when granted will provide the company with an unrivalled IP position in the human antibody space.
arGEN-X’ SIMPLE Antibody™ platform utilizes the active immunization of outbred Camelids with a target antigen to rapidly deliver highly diverse antibodies whose variable regions are nearly identical to those of human antibodies. arGEN-X then uses these to produce variable antibody regions with 96-99% human sequence homology via minimal germlining (humanization). This is easily achieved without any loss in affinity and potency in just a matter of weeks. These variable domains are then combined with human constant domains to generate full size, fully human therapeutic antibodies.
A further key attraction of the SIMPLE Antibody™ platform is its unique ability to generate incredibly diverse panels of ultra-potent antibodies to a broad range of targets, including intractable and conserved targets. These antibody panels effectively blanket the target of interest providing pharma researchers with more choice in the drug discovery stage. This allows them to use more stringent lead selection criteria, increasing the probability of successful therapeutic antibody development.
arGEN-X has already demonstrated that human antibodies generated using its SIMPLE Antibody™ platform routinely exhibit gold standard potencies and affinities, without the need for additional engineering. These properties combined with their excellent manufacturability, make them an ideal starting point for a therapeutic antibody development program.
Prof. Hans de Haard, CSO of arGEN-X commenting on today’s announcement said:
“The UKPTO’s decision to grant the first patent for our SIMPLE Antibody™ platform is a major value-enhancing milestone in arGEN-X’ corporate development. It is also a key step in our goal to achieve a broad and unencumbered global IP position for our platform which will give us a highly competitive position in the human antibody space”.
“As we work with our SIMPLE Antibody™ platform, we are increasingly convinced that it will transform the discovery and development of human therapeutic antibodies. This is due to its ability to rapidly produce incredibly diverse panels of ultra potent antibodies that address a broad range of both intractable and conserved targets. These unique properties are already generating considerable interest amongst potential partners who are looking to access a platform around which they can build broadly based therapeutic antibody discovery and development programs.”
arGEN-X is currently using the power of the SIMPLE Antibody™ platform to build its business by making this unique technology and know-how available to biopharmaceutical companies through selective strategic partnerships and by developing its own portfolio of exciting therapeutic antibody candidates.
The power of the SIMPLE Antibody™ platform is enabling the Company to rapidly build its own pipeline. arGEN-X’ lead product, ARGX-109, a fully human mAb targeting autoimmune, inflammation and oncology indications, has already entered preclinical development in less than 12 months from start of the discovery process. ARGX-109, which targets the cytokine IL-6, has already shown very high potencies in a range of in vivo studies. arGEN-X currently has a further three therapeutic antibody candidates in its own development pipeline.
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• SIMPLE Antibody™ Platform delivers unprecedented choice of ultra-potent functional antibody leads against challenging soluble and cell surface targets.
• ARGX-109, a fully human mAb targeting autoimmune, inflammation and oncology indications, enters preclinical development in less than 12 months from start of discovery.
Rotterdam, the Netherlands, March 1, 2010 – arGEN-X, a biopharmaceutical company focused on the discovery and development of human monoclonal antibodies using its proprietary SIMPLE Antibody™ platform, announces that it will provide an update on the development of this unique platform and its own antibody pipeline during the BIO-Europe Spring event in Barcelona (March 8-10, 2010).
Tim Van Hauwermeiren, the CEO of arGEN-X, will highlight a series of important technical breakthroughs during his presentation, demonstrating the power of the Company’s SIMPLE Antibody™ platform to deliver multiple, diverse, ultra-potent functional antibodies that are able to blanket any target, regardless of its complexity.
He will also outline the very rapid progress that arGEN-X has made in building its own pipeline with its lead product ARGX-109, which entered preclinical development less than 12 months from the start of the discovery process. ARGX-109 was chosen from a panel of 65 functional antagonists generated against IL-6, a cytokine that plays an important role in several autoimmune, inflammation and oncology indications.
arGEN-X’ SIMPLE Antibody™ Platform is based on the active immunisation of outbred Camelids with target antigen to deliver antibodies whose variable regions are virtually identical to those of human antibodies. These variable domains are combined with human constant domains to generate full size, fully human therapeutic antibodies.
SIMPLE Antibodies routinely exhibit gold-standard potency and manufacturability without the need for additional engineering, making them an ideal starting point for a therapeutic antibody development program.
Prof. Hans de Haard, CSO of arGEN-X commenting on the SIMPLE Antibody™ platorm said:
“The work that we have conducted in the past six months has clearly demonstrated the power of our SIMPLE Antibody™ platform and its potential to transform the development of therapeutic antibodies. We have tested its full potential by selecting as targets two highly challenging receptors known to play a pivotal role in cancer. In just a matter of weeks, we managed to generate an incredibly diverse panel of ultra-potent antagonist antibodies, effectively blanketing these targets in a way that, according to our expert collaborators, has never been seen before. Given the outstanding manufacturability of our human antibody leads, we are now in a position to further develop candidates with the best possible drug characteristics in record time.”
arGEN-X intends to use the power of the SIMPLE Antibody™ platform to build its business by making its technology and know-how available to biopharmaceutical companies through selective strategic partnerships and adding more exciting programs to its preclinical portfolio.
Tim Van Hauwermeiren, CEO of arGEN-X commenting on the progress with the Company’s own antibody pipeline said:
“Our lead program has already been remarkably productive, identifying 65 unique IL-6 antagonists with potencies in the picomolar to femtomolar range. Both lead and back-up molecules in this program have shown impressive performance in in vivo efficacy studies less than a year from project commencement, and are now being progressed into preclinical development. We are extremely pleased with how quickly we have progressed all four of our internal programs. The progress that we have made so far with our platform and pipeline gives us great confidence in building a high-value business that makes us an attractive partner for big pharma.”
The power of the SIMPLE Antibody™ platform has enabled arGEN-X to close a recent €12.5 milion Series A fund raising. The round was backed by a range of leading European life science investors including Forbion Capital Partners, LSP, Crédit Agricole Private Equity, KBC Private Equity, BioGeneration Ventures, Erasmus MC Biomedical Fund, Thuja Capital Healthcare Funds, as well as the prestigious Belgian life sciences research institute VIB.
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Rotterdam, The Netherlands, December 3rd 2009 – arGEN-X BV, a biopharmaceutical company focused on the discovery and development of human antibodies using its proprietary SIMPLE Antibody™ platform, today announced the successful second closing of its Series A equity financing round. The Company raised an additional EUR 3.0 million (~USD 4.5 million) from two leading life science investors, Crédit Agricole Private Equity and VIB (the prestigious Flemish research institute).
arGEN-X has raised a total of EUR 12.5million (~USD 18.7 million) from its completed Series A equity financing round, which was heavily oversubscribed.
Philippe Guinot MD, PhD, a senior partner at Crédit Agricole Private Equity, joined the arGEN-X Supervisory Board.
The Series A round was co-led by Forbion Capital Partners (The Netherlands) and LSP (Life Sciences Partners – The Netherlands). Other members of the syndicate, which invested in the first closing of EUR 9.5 million, were KBC Private Equity (Belgium), BioGeneration Ventures (The Netherlands) and existing shareholders Erasmus MC Biomedical Fund and Thuja Capital Healthcare Funds.
arGEN-X will use the proceeds to further develop the Company’s proprietary, unencumbered SIMPLE Antibody™ engine and to continue to build a proprietary pre-clinical antibody product portfolio. arGEN-X’s SIMPLE Antibody™ platform yields monoclonal antibodies which combine an unparalleled functional diversity against human disease targets with best in class human germline homology. arGEN-X’s SIMPLE Antibodies™ are generated in vivo, starting from active immunization, and exhibit ultra high starting affinities and potencies without the need for further engineering.
The arGEN-X platform has the potential to rapidly create exciting product candidates both against novel therapeutic targets and against targets where standard antibody approaches fail to generate an optimal lead diversity.
Philippe Guinot MD, PhD, Senior Partner at Crédit Agricole Private Equity commented: “We believe that arGEN-X has a truly innovative technology and a management team with an impressive track record of building a valuable business in the antibody area. It is no surprise to us that the Company was able to attract such a high-quality syndicate of investors for its Series A round and Crédit Agricole Private Equity is delighted to have had this opportunity to participate at this important early stage of the arGEN-X’ development.”
Tim Van Hauwermeiren, Chief Executive Officer of arGEN-X added: “We are very pleased to have raised this additional funding from two experienced European life science investors. In addition, we are proud to become VIB’s first external investment and we view this as a real quality stamp of approval. With substantial funding now in place, arGEN-X is well positioned to execute its ambitious value-creating strategy over the next two years,.”
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Rotterdam, The Netherlands, November 10th 2009 – arGEN-X BV, a biopharmaceutical company focused on the discovery and development of human antibodies using its proprietary SIMPLE Antibody™ platform, today announced that it has opened a new R&D subsidiary in Flanders – arGEN-X BVBA. The facility is supported by a €1.3 million grant from the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) and is intended to become a center of excellence dedicated to the discovery and development of novel therapeutic antibodies based on arGEN-X’ SIMPLE Antibody™ platform.
The facility will operate under arGEN-X’ CSO Prof. Dr. Hans de Haard, and CDO Dr. Torsten Dreier, who have already attracted an experienced international core team of antibody discovery and development as well as project management experts. Among those recently appointed is Dr Michael Saunders, who has joined arGEN-X as Senior Director Targets & Programs, bringing important relevant experience from within GlaxoSmithKline in target identification and project management.
Under this leadership, the Company is in the process of building an international team of around 25 leading antibody scientists to be based at this facility.
Prof. Dr. Hans de Haard, CSO of arGEN-X, commenting on this announcement said: “We have chosen to locate our R&D facility in what is the heart of the Benelux Biotech cluster and in a region with well-established infrastructure and expertise from which arGEN-X can draw. We are grateful to the Flemish government for providing a grant to help facilitate our move and are progressing towards building a world-leading antibody discovery and development capability. We are confident that we can create a center of excellence in Flanders, which will serve as a magnet to some of the best antibody talents globally who will be attracted by the clear potential of arGEN-X’ SIMPLE Antibody™ platform.”
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Rotterdam, The Netherlands, November 3rd 2009 – arGEN-X BV, a biopharmaceutical company focused on the discovery and development of human antibodies, today announced that its newly formed R&D subsidiary arGEN-X BVBA has received a grant worth €1.3 million to further develop its novel SIMPLE Antibody™ platform. The grant was awarded by the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT).
arGEN-X’s SIMPLE Antibody™ (Superior Immunodiversity with Minimal Protein Lead Engineering) platform has potential as a discovery engine for novel therapeutic monoclonal antibodies that combine unparalleled functional diversity against human disease targets with best-in-class human germline homology.
In the 12 months that the Company has been operational, it has delivered a robust proof of concept for its breakthrough, proprietary SIMPLE Antibody™ platform and progressed its lead program, targeting inflammatory and oncology indications, to in vivo proof of concept. In addition, the Company has filed and prosecuted broad patent protection for its platform technology.
Tim van Hauwermeiren, CEO of arGEN-X, said: “The SIMPLE Antibody™ platform has the potential to rapidly create new product candidates both against novel therapeutic targets and against targets where standard antibody approaches fail to generate optimal lead diversity. We are very pleased to receive this grant from the IWT, which, in conjunction with the substantial series A fundraising we completed recently, will allow us to continue the rapid development and validation of this exciting discovery platform.”
Prof. Dr. Hans de Haard, CSO of arGEN-X added: “The SIMPLE Antibody™ platform has the potential to set a new standard in the fully human antibody space in terms of functional diversity as compared to the currently established technologies. This IWT grant will allow us to further develop the key competitive features of the SIMPLE Antibody™ platform and to initiate additional programs that are situated in the sweet spot of our proprietary antibody platform.”
Note for the editor
About arGEN-X – www.arGEN-X.com
arGEN-X is a research stage biopharmaceutical company with a broadly applicable, proprietary SIMPLE Antibody™ platform. The platform allows arGEN-X to create an unparalleled diversity of in vivo generated antibody leads against a broad range of human disease targets. This superior choice of ultra-high affinity and highly potent leads, having best-in-class human homology, allows for more stringent lead selection criteria, thereby increasing the probability of success later in the drug development path. The Company has validated its monoclonal antibody platform on two human disease targets and has broad patent claims in place covering its technology.In September 2009, arGEN-X has raised €9.5 million in the first closing of a Series A financing. This fund raising was supported by a number of experienced life science investors including Forbion Capital Partners (The Netherlands) and LSP (Life Sciences Partners – The Netherlands), KBC Private Equity (Belgium), BioGeneration Ventures (The Netherlands) as well as existing shareholders Erasmus MC Biomedical Fund and Thuja Capital Healthcare Funds.
arGEN-X™ and SIMPLE Antibody™ are deposited trademarks of arGEN-X BV.
SIMPLE stands for Superior Immunodiversity with Minimal Protein Lead Engineering.
About IWT – Flanders – www.iwt.be
The agency for Innovation by Science and Technology (abbreviated as IWT) is the government agency founded in 1991 by the Flemish Government to support technological innovation projects in Flanders. In 2008 IWT distributed a total of
€311 million in subsidies for innovation projects to companies, organizations, research and educational institutions in Flanders. In addition to financial support, IWT also assists companies by, for instance, helping them find the right information or the right partners at home or abroad and providing assistance with the preparation of projects for European programmes. IWT also has an important coordination mandate aimed at promoting close cooperation among all the actors involved in technological innovation in Flanders.For further information, please contact:
Citigate Dewe Rogerson (for arGEN-X)
David Dible
Mark SwallowT: +44 207 282 2949/2948
E: David.Dible@citigatedr.co.ukarGEN-X
Tim Van Hauwermeiren, MSc, eMBA
Chief Executive OfficerT: +31 6 122 85 257
E: tim.vh@arGEN-X.comIWT
Monique Baeteman
PR & CommunicationmanagerT: +32 2 209 09 29
E: mb@iwt.be
Press releases
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29 – 30th September 2010, Radisson Blu Hotel, Zurich Airport
