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«Nous sommes une petite entreprise avec un large portefeuille»

05.02.2019

Martine et Jean-Paul Clozel ont créé Actelion en compagnie de deux autres fondateurs, puis en ont fait la plus grande société biotechnologique d’Europe. Actelion et son pipeline de produits en phase finale ont été rachetés par Johnson & Johnson en 2017. A partir des actifs de recherche et développement d’Actelion qui en étaient à l’étape de découverte ou à un stade initial, le couple a alors créé Idorsia, avec l’ambition de bâtir l’une des plus grandes sociétés biopharmaceutiques d’Europe.

Nous nous sommes retrouvés avec Martine Clozel afin d’évoquer sa passion pour la recherche, le point de vue médical sur la science et les besoins des entrepreneurs en devenir dans le secteur des biotechnologies.

BaselArea.swiss: Martine, Idorsia est-elle la nouvelle Actelion?

Martine Clozel: En partie, oui. Nous continuons à réaliser des choses complexes. En ce sens, rien n’a changé. Notre culture et nos objectifs sont les mêmes qu’au sein d’Actelion: nous désirons trouver de nouveaux médicaments innovants, capables d’avoir un impact important sur la vie des patients. Nous sommes vraiment ravis de poursuivre notre travail de découverte de médicaments. C’est fantastique de pouvoir le faire. L’enthousiasme s’exprime à travers toute l’entreprise, je le vois. Actelion était devenue une grosse société biopharmaceutique, présente dans de nombreux pays. Idorsia, quant à elle, est basée à Allschwil et se concentre sur l'efficacité des activités de recherche et développement. Cela dit, nous pensons déjà à la phase commerciale; nous avons récemment embauché un directeur commercial et ouvert un premier bureau à l'étranger, en l'occurrence au Japon.

Vos décisions concernant votre portefeuille sont-elles uniquement guidées par la science? Ou prenez-vous en considération certains facteurs commerciaux?

Nous savons tous que les besoins médicaux sont immenses pour ce qui touche à l’insomnie, au lupus ou à l’hypertension. Le choix d’une nouvelle indication clinique dépend de la nouvelle molécule, de son mécanisme d’action et de là où la molécule peut avoir l’impact le plus fort en tant que nouvelle thérapie. Nous essayons de faire preuve de beaucoup de pragmatisme et d’emprunter la direction que nous montre la science. En phase II et au‑delà, lorsque nous commençons à avoir une meilleure compréhension et à constater que notre hypothèse se confirme en matière de sécurité et d'efficacité, nous pouvons nous lancer dans le positionnement du médicament en vue de sa mise sur le marché et de son potentiel commercial.

Quelle est votre approche en matière de projets d’acquisition ou de cession de licences?

Nous n’acquérons aucune licence, car nous développons quantité de projets internes fascinants. A l’heure actuelle, dix de nos composés sont en phase de développement clinique. Par ailleurs, plusieurs projets de recherche progressent vers le développement. Toutefois, nous menons des activités en vue de signer des accords de cession de licences – pas parce que ces projets ne sont plus d’intérêt prioritaire, mais parce que notre organisation est bien plus petite qu’avant. Nous ne disposons plus que d’un tiers des capacités de développement clinique que nous possédions par le passé et nous ne pouvons donc pas tout gérer. Nous sommes une petite entreprise dotée d'un large portefeuille.

Etes-vous entièrement focalisés sur vos projets internes? Ou recherchez-vous aussi des collaborations externes?

Nous recherchons des solutions sur mesure. Si nous identifions quelque chose qui peut nous aider, nous collaborons volontiers avec des partenaires externes, que ce soit des universités, des sociétés biotechnologiques ou d’autres entités. En fait, nombre de nos projets débutent à la lecture d’un article ou en tombant sur de nouvelles données intéressantes, sur lesquelles nous avons envie de travailler.

Sur votre site web, vous abordez en premier lieu les symptômes des patients lorsque vous décrivez une maladie, et vous évoquez la science seulement dans un deuxième temps. Comment veillez-vous à toujours rester proches des patients, tant vous-même que vos collaborateurs?

Nous sommes très proches des gens qui sont proches des patients, comme les docteurs, les infirmières, etc. Nous écoutons attentivement et essayons réellement de comprendre les patients. Nous invitons également des patients à nous rencontrer. Je suis docteur en médecine. J’ai donc naturellement un point de vue médical sur tout ce que nous entreprenons dans le domaine de la recherche. C’est l’une des caractéristiques d’Idorsia.

En parlant de collaborateurs, est-il facile de recruter les bonnes personnes?

Ce n’est pas facile, mais c’est partout pareil. Personnellement, j’adore la pharmacologie. C’est fantastique de pouvoir aider les patients, d’en traiter des milliers. C’est vraiment génial et pourtant, tout le monde n’en a pas conscience. Il y a un vrai manque de communication autour de l’intérêt de la recherche pharmaceutique, qu’il s’agisse des améliorations de l’espérance de vie, des révolutions dans le domaine de l’oncologie ou de l’amélioration de la qualité de vie. Tout n’est que progrès. Nous devons parler davantage de l’importance du secteur pharmaceutique pour attirer les prochaines générations de talents.

Il semble que les sociétés biotechnologiques américaines sont plus prospères en restant indépendantes. Quelle en est la raison à votre avis?

Je ne suis pas sûre que cela soit vrai au vu des acquisitions récentes de Celgene, Tesaro, Kite et Loxo par BMS, GSK, Gilead et Eli Lilly, respectivement. Pour n’en citer que quelques‑unes. A l’heure actuelle, les sociétés biotechnologiques restent rarement indépendantes, même aux Etats-Unis, simplement parce que les grandes entreprises s’appuient largement sur leurs découvertes. Avec Actelion, nous avions une vision à long terme ambitieuse. Nous n’avons jamais eu pour objectif de nous faire racheter. Au contraire, nous voulions créer une structure – pas seulement une molécule ou une technique – mais une organisation, qui soit en mesure de découvrir de nombreux médicaments. Nous étions ambitieux et nous prenions des risques, ce qui est relativement rare. Peut-être les sociétés biotechnologiques américaines affichent-elles un peu plus cette ambition, mais l’Europe présente des particularités que le secteur devrait mettre à profit. Par exemple, l’industrie chimique en Suisse et en Allemagne est exceptionnelle. D’une manière générale, l’Europe ne manque pas de travaux scientifiques passionnants et de personnes de talent.

En quoi est-ce gratifiant pour vous de travailler dans une start‑up plutôt qu’une grande entreprise?

Une petite organisation offre plus de liberté et, surtout, plus de proximité entre les faits et la prise de risques. Notre portefeuille est suffisamment modeste pour que la direction connaisse tous les projets. Nous pouvons être très efficaces dans la prise de décisions, ce qui est beaucoup plus compliqué dans les grandes entreprises.

Quel serait votre conseil pour lancer une société biotechnologique?

Il faut penser en même temps à survivre et à être rentable. Adopter une vision large, à court et à long terme, sans se focaliser uniquement sur la prochaine étape, mais en voyant les choses en grand dès le début. Faire preuve de pragmatisme dans les décisions. Et plus particulièrement, ne pas faire les choses seul, s’entourer d’une équipe.

Au sujet du choix d’un partenaire, vous avez créé Actelion et Idorsia avec votre mari. Comment passez-vous du laboratoire à la table à manger?

Mon mari et moi, nous nous connaissons depuis très longtemps. Nous avons en commun la passion de la recherche et de l’aide aux patients. J’ai toujours apprécié de pouvoir discuter des difficultés, mais aussi de partager de nombreux bons moments avec Jean-Paul. Bien évidemment, nous travaillons beaucoup et sommes très impliqués – comme tout le monde chez Idorsia. Nous tentons de tracer une limite claire entre le bureau et la maison, surtout quand nos enfants et petits-enfants nous rendent visite. Nous voulons être disponibles pour eux. C’est difficile, mais nous ne pensons pas constamment au travail et n’en parlons pas tout le temps.

Serez-vous encore à la recherche du prochain médicament dans dix ans?

Je ne pense pas. Je n’ai pas envie de travailler toute ma vie. Un jour ou l’autre, j'aimerais avoir plus de temps à consacrer à ma famille et à mes amis.

Actelion n’est pas seulement connue pour ses médicaments, mais aussi pour son édifice emblématique. Idorsia est domiciliée dans un édifice conçu par Herzog & de Meuron. L’architecture est-elle importante à vos yeux?

Très importante. Ces édifices se dresseront là pendant de nombreuses années. Ils font partie de la culture et du style de Bâle. La Suisse, et Bâle en particulier, sont à l’avant-garde en matière d’architecture. Nous sommes heureux d’avoir pu y participer. L’architecture est le symbole de l’innovation à laquelle nous aspirons. Nous souhaitons que nos collaborateurs travaillent dans de bonnes conditions, avec beaucoup de lumière et de nombreuses possibilités d’interaction – après tout, nous passons un temps considérable au bureau.

Nous avons entendu une histoire drôle au sujet du nom Idorsia, qui serait l’acronyme de «I do research in Allschwil». Quelle est la vraie histoire de ce nom?

J’aime bien cette histoire. En réalité, nous avons eu l’occasion d'utiliser l’un des noms de produits que nous avions déjà protégés, ce qui nous a donné une bonne base de départ pour assurer le nom de l’entreprise.

report Life Sciences

The pharma centers of Basel and India are influencing each other

21.02.2020

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Roche builds “best research center in the world”

20.02.2020

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«Notre activité est la plus belle du monde»

04.09.2018

Le parcours de Giacomo di Nepi est impressionnant: ancien cadre supérieur de grandes entreprises, il s’est orienté vers les biotechnologies et assume actuellement la fonction de CEO de Polyphor, dont il a orchestré l’introduction en bourse en mai 2018. Nous nous sommes entretenus avec Giacomo sur le service aux patients, le timing d’une introduction en bourse et le personnel dont les sociétés actives dans les biotechnologies ont besoin.

BaselArea.swiss: Que suivez-vous actuellement – vos e-mails ou l’évolution boursière?

Giacomo di Nepi: Les e-mails et les réunions sont encore ma priorité. Je garde bien entendu un œil sur la Bourse, mais la volatilité est telle que je n’essaie plus d’interpréter le marché à court terme. Je suis néanmoins l’évolution de l’action et m’engage clairement à faire en sorte qu’elle s’apprécie et apporte une plus-value aux actionnaires qui nous ont fait confiance et investi dans nos idées, notre technologie et notre équipe.

Vous avez travaillé dans de grandes entreprises telles que McKinsey et Novartis. Qu’est-ce qui vous a incité à rejoindre une start-up comme Polyphor?

C’est vrai, j’ai travaillé dans des multinationales, mais aussi dans d’autres sociétés. Mon dernier poste était chez InterMune, une société californienne active dans les biotechnologies. J’ai lancé ses activités européennes à partir de rien, depuis mon domicile. Lorsqu’il faisait beau, nous tenions nos réunions dans le jardin plutôt que dans la salle à manger. Cette société est devenue une entreprise de 200 personnes concentrées sur un médicament destiné aux patients atteints de fibrose pulmonaire idiopathique. Dans une start-up, on peut appréhender toutes les dimensions d’une société d’un point de vue beaucoup plus large. C’est ce qui m’a séduit chez Polyphor, mais d’autres raisons m’y ont aussi attiré.

A savoir...?

… la science absolument fantastique qui est sans aucun doute l’un de ses piliers. Polyphor est une entreprise qui a découvert la première nouvelle classe d’antibiotiques contre les bactéries à Gram négatif des 50 dernières années. C’est une innovation fondamentale. La résistance aux antibiotiques devient un problème critique. Certains patients contractent une infection, puis sont traités avec 20 médicaments différents mais meurent quand même. C’est inacceptable. A l’heure actuelle, la pneumonie à Pseudomonas aeruginosa a un taux de mortalité de 30% à 40%. De même, si une femme atteinte d’un cancer du sein métastatique est traitée en chimiothérapie de troisième ligne, elle ne dispose que de rares options thérapeutiques et son pronostic est très sombre. Nous voulons sauver des vies et donner plus de temps aux patients. Pour moi, c’est à cause de cela que notre activité est la plus belle du monde. Cela me brise le cœur de voir ces patients.

Donc vous rencontrez des patients?

Oui, bien sûr. J’ai récemment invité une patiente chez Polyphor: une femme exceptionnelle souffrant d’une colonisation de Pseudomonas qui participé aux essais cliniques précédents. Son formidable courage et sa volonté de se battre pour vivre sont très émouvants et une source d’inspiration pour chacun d’entre nous. Elle nous a parlé de son expérience, car je pense que chacun devrait pouvoir ressentir ce que nous essayons de réaliser, surtout ceux qui ne sont pas directement impliqués dans le développement, par exemple le personnel comptable qui ne voit normalement que les factures liées aux essais cliniques.

D’une société de recherche, Polyphor s’est transformée en une entreprise biopharmaceutique axée sur l’activité de R&D (recherche et développement) au cours des dernières années. Comment l’organisation a-t-elle digéré cette mutation?

En passant d’une étape à l’autre, on place la barre de plus en plus haut parce que le développement implique des projets pluriannuels complexes qui requièrent d’énormes investissements. Il faut vraiment changer d’état d’esprit. En ce qui me concerne, j’aime le changement. L’administration ne m’intéresse pas vraiment. D’ailleurs, ce changement-là était essentiel. Cela dit, nous avons encore une importante activité de recherche spécialisée dans les antibiotiques et l’immuno-oncologie, dont l’ambition est de trouver et créer d’excellents composés.

Bâle semble être devenue une zone-clé pour les antibiotiques dernièrement.

Les antibiotiques ont été négligés par de nombreuses grandes entreprises. A l’instar du principe de Pascal : tout vide peut être comblé. Aujourd’hui, de petites firmes avec un fort esprit d’entreprise deviennent des leaders mondiaux – et Bâle joue un rôle clé à cet égard. C’est sûr, nous bénéficions d’une très bonne base scientifique à Bâle. A mon avis, Bâle est l’endroit idéal pour faire de la R&D. Et je ne serais pas surpris de voir les grandes entreprises revenir...

Polyphor est cotée à la SIX Swiss Exchange depuis mai 2018, générant un produit brut d’introduction de 165 millions de francs suisses. Est-ce qu’une introduction en bourse était l’option optimale pour Polyphor?

Avec un peu de chance, une société active dans les biotechnologies a un produit qui n’est plus qu’à un pas de la commercialisation. Nous en avons deux: notre antibiotique Murepavadin a commencé la phase III pendant notre négociation d’un programme avec la FDA (Food and Drugs Administration américaine) autorisant le lancement de notre médicament immuno-oncologique Balixafortide sur le marché avec une seule étude pivot. Nous sommes donc dans une situation unique. Mais ces études exigeaient des capitaux importants. Depuis notre introduction en bourse, nous disposons des ressources pour développer nos produits et, s’ils répondent aux attentes, les mettre à disposition des patients qui en ont besoin. L’IPO (initial public offering) était un passage obligé à ce stade de notre évolution.

Quelles conditions ont dû être remplies en vue de l’IPO?

Une introduction en bourse est une opération intéressante. C’est un peu comme si l’on passait une visite médicale complète. Les investisseurs ne connaissent pas la société, mais nous voulons qu’ils soutiennent nos idées, notre vision et notre équipe. Cela signifie qu’ils doivent nous faire confiance. Pour acquérir cette confiance, nous devons être complètement transparents et expliquer en détail l’activité de la société ainsi que les risques et opportunités auxquels elle fait face. Au final, les résultats ont été exceptionnels parce que nous étions la plus grande IPO biotechnologique de Suisse des dix dernières années. De plus, nous étions parmi les trois leaders européens au cours des trois dernières années,

Quel rôle a joué le timing?

Le timing est important, mais pas critique. Le premier trimestre 2018 était excellent pour les IPO mais le deuxième trimestre n’était pas fantastique. Une douzaine de sociétés a été introduite en bourse pendant cette période. Il se peut qu’une IPO valide doive être reportée si le timing n’est pas idéal. Mais on ne procède jamais à une IPO non valide à cause d’un timing parfait.

Quelles ont été les réactions à l’IPO de Polyphor?

A l’interne, nous sommes ravis de pouvoir nous employer à mettre nos médicaments à disposition des patients. Mais nous restons conscients de notre responsabilité et réaffirmons notre engagement. En externe, notre introduction en bourse démontre bien les capacités de la Suisse et surtout de Bâle dans le domaine pharmaceutique. L’IPO était une phase de haute visibilité, de reconnaissance publique. D’une certaine manière, une introduction en bourse révèle l’intensité en investissement de cette activité. J’espère que notre capacité à lancer de nouvelles sociétés, à les faire prospérer et à mettre de nouvelles thérapies à disposition des patients est un bon signe pour l’ensemble du secteur.

Pourquoi avez-vous choisi la bourse suisse?

Comme nous avions déjà une importante base d’actionnaires en Suisse, il nous a semblé tout naturel de demander notre cotation à la bourse suisse. Notre société est connue ici. La Suisse est un marché fantastique, je suis ravi de notre choix. A vrai dire, je me demande pourquoi si peu d’entreprises s’y engagent. Les fonds y abondent et il y a des investisseurs versés dans le secteur pharmaceutique et disposés à y prendre des risques.

Quels sont les projets de Polyphor à moyen terme?

Notre vision est claire: Nous voulons devenir un leader dans le domaine des antibiotiques et contribuer à contrer et réduire la menace que posent les pathogènes multipharmacorésistants. Parallèlement, nous voulons faire progresser une nouvelle classe de médicaments immuno-oncologiques. Nous développons des thérapies de troisième ligne contre le cancer du sein métastatique. Les femmes qui en souffrent disposent de très rares options thérapeutiques. Mais nous estimons que le potentiel de ce médicament peut dépasser le cadre de cette population de patients, par exemple pour les premières lignes du cancer du sein ou d’autres combinaisons et indications. Cela nous ferait entrer sur un marché beaucoup plus concurrentiel.

Comment pourrez-vous franchir le pas?

Nous devons veiller à ce que notre organisation et notre culture soient appropriées pour effectuer nos études de manière efficace. Nous voulons faire en sorte que tous les rouages organisationnels fonctionnent et que nous ayons toutes les compétences requises.

Comment allez-vous y parvenir?

Les talents sont, à mon avis, un élément-clé de la réussite d’une société, voire l’unique facteur de réussite. Je consacre donc beaucoup d’efforts et d’engagement à la recherche de talents. Je conduis deux ou trois entretiens avec certains candidats, cela ne me dérange pas. Ils ont aussi des entretiens avec leurs futurs collègues. Quand je travaillais chez Novartis, j’ai eu d’excellentes expériences avec les jeunes talents. Pourquoi? Parce qu’ils ont à la fois l’intellect et les capacités. Il importe peu qu’ils aient une expérience limitée puisque le reste de l’organisation en abonde. A l’inverse, en biotechnologie, il est impératif de recruter des personnes dotées de l’expérience pertinente car les autres collaborateurs n’en disposent pas encore.

Quel changement culturel intervient quand on passe d’un grand groupe pharmaceutique à une société active dans les biotechnologies?

L’expérience n’est qu’un morceau du puzzle. J’ai rencontré beaucoup de candidats chevronnés – mais incapables de faire une photocopie ou de travailler à moins d’avoir trois subalternes. Il ne conviennent pas non plus.Je recherche donc des personnes ayant un profil quasiment «schizophrénique»: en biotechnologie, on a besoin de collaborateurs qui conjuguent expérience, capacité et vision mais sont aussi disposés à retrousser leurs manches, prennent des décisions pratiques et travaillent indépendamment.

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Allthings cooperates with Garaio REM

13.02.2020

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Basel startups to present business concepts in India

11.02.2020

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Basler Pharmafirmen gehen bei Investitionen voran

15.07.2018

Basel - Die 24 Pharmakonzerne, die Mitglieder beim Verband Interpharma sind, haben im vergangenen Jahr 7 Milliarden Franken für Forschung und Entwicklung in der Schweiz ausgegeben. Dabei gehen Roche und Novartis voran.

Die 24 Interpharma-Konzerne haben 2017 weltweit insgesamt 96 Milliarden Franken für Forschung und Entwicklung ausgegeben. In die Schweiz flossen davon 7 Milliarden Franken. Damit übersteigen ihre Schweizer Forschungsinvestition den Umsatz, den sie in der Schweiz erzielen, um mehr als das Doppelte. Dies belegt laut dem Verband die grosse Bedeutung des Forschungsstandorts Schweiz und den Innovationsgedanken innerhalb der Firmen.

Insbesondere Firmen in der Schweiz wie Roche und Novartis haben viel für Forschung und Entwicklung am Standort Schweiz ausgegeben. Aber auch Firmen ohne Schweizer Hauptsitz wie Johnson & Johnson tätigten den Angaben zufolge grosse Investitionen. Zusätzlich zu den Investitionen in die Forschung haben die Unternehmen rund eine halbe Milliarde Franken für Anlagen wie technische Geräte, Maschinen, Gebäude- und Betriebsausstattung ausgegeben.

Interpharma betont in einer Medienmitteilung zur Studie auch die wichtige Rolle der Pharmabranche für die Schweizer Exportwirtschaft. Ausserdem hebt der Verband hervor, dass zwischen 2012 und 2016 aus der Schweiz über 86 Patente pro Million Erwerbstätige in der pharmazeutischen Forschung angemeldet wurden. Das sind doppelt so viele wie in Dänemark und fast fünfmal so viele wie in Deutschland.

In der Studie sind auch die Umsätze der untersuchten Firmen aufgeführt worden. Hinter Pfizer (47,4 Milliarden Dollar) folgt bereits Novartis (46,6 Milliarden Dollar). Roche (39,9 Milliarden Dollar) belegt hinter Johnson & Johnson und Sanofi den fünften Rang. ssp

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FutureHealth conference brings international experts to Basel

29.01.2020

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New test protects mother and child

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“Basel has all the ingredients required to host a successful company”

11.06.2018

The physician and pharmacologist Nicole Onetto is a member of the Board of Directors at the Basilea Pharmaceutica AG. In the Interview that was featured in Basilea’s annual report she talks about current challenges in oncology.

Great strides are being made in the long-term treatment of oncology patients. As an oncology expert, what do you find to be the most important advancements in the industry?

Nicole Onetto: We see spectacular results in terms of long-term survival in quite a few diseases where, less than ten years ago, there were no new treatments available. And for many forms of cancer, where previously we had only access to traditional therapies such as surgery, radiation therapy and chemotherapy, we have been able to take advantage of the new molecular understanding of cancer to personalize the treatment for each patient. This has facilitated the development and the utilization of targeted therapies associated with superior efficacy and reduced toxicity compared to traditional treatments. Finally, in the last few years, we have been able to harness the potential of the immune system to develop new therapeutic approaches which stimulate our own immune defenses to control cancer growth.

What do you see as the next major treatment improvements that may be achieved in the short and mid-term?

Definitely the further development of immune therapies for cancer patients seems more and more important. These new modalities will need to find the right place in the management of patients and will have to be used in combination with more traditional therapies. The cost-effectiveness of these innovative technologies will also need to be evaluated. Another very important topic will be minimizing toxicity of treatments and avoiding over-treatment.

How can companies succeed in clinical development?

With a more personalized approach to cancer treatment, new opportunities do exist to develop drugs associated with high efficacy in well-defined patient populations. However, drug development will always require patience, perseverance and scientific rigor. Many challenges still remain in treating cancer patients, despite the important progress that has been made. Among others issues, drug resistance is a significant hurdle and continues to be in the focus of Basilea. For patients with resistant diseases, not so long ago, the only possible approach was to change to a new drug, often a new chemotherapy. Now we have gained more insight into the mechanisms of resistance. In addition, many researchers all over the world are investigating the best ways to circumvent treatment resistance. Other important factors are collaborations between academia and the private sector such as companies like Basilea, to develop new innovative drugs to benefit patients.

How can this be supported?

The use of biomarkers to help choose the most appropriate treatment regimen and to select the patients with the highest probability of response to treatment has and will continue to have a major impact on the development of new cancer agents. Biomarker data are key to the design of development plans of new drugs and to go/no go decisions. These data are now often incorporated in the approval process and subsequent commercialization of new drugs. This approach, based on scientific evidence to select new drugs, is one of the major advances that are currently transforming the research and development process as well as clinical study methodology.

Do you see advantages for Basilea being located in Basel?

Basel has all the ingredients required to host a successful company: a vibrant research community, an international reputation of excellence in the pharma industry, a pool of talented people and a strong and stable economy. Basel is a leading life-science hub with the presence of an excellent university, the headquarters of established large pharmaceutical companies and many start-ups and innovative ventures. There are many similarities between Basel and the few well established biotechnology hubs in Europe and North America. This favorable environment has already helped Basilea build a very strong company and should continue to support its further success. So I am delighted to have been elected by Basilea’s shareholders as a member of the board and look forward to playing an active role in the Basel biotech community.

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NBE-Therapeutics raises 22 million dollars

10.01.2020

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Sotio opens office in Basel

09.01.2020

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«J’aime réfléchir à des problèmes apparemment insolubles»

13.03.2018

Andreas Plückthun continue de chercher là où d’autres ont laissé tomber: 40 collaborateurs travaillent au sein de son laboratoire dans le domaine de l’ingénierie des protéines. Les résultats constituent la base de trois entreprises de biotechnologie: Morphosys à Munich ainsi que Molecular Partners et G7 Therapeutics (désormais Heptares Zürich) à Schlieren. En marge du congrès Antibody à Bâle, Andreas Plückthun nous a expliqué pourquoi il est resté fidèle à la recherche.

Monsieur Plückthun, en trois décennies, vous avez co-fondé trois sociétés de biotechnologie. Quels ont été les ingrédients de cette réussite?

Au début, il y avait toujours la curiosité de découvrir quelque chose de nouveau, jamais la volonté de créer une entreprise. Après que nous ayons fabriqué des anticorps artificiels et appris comment imiter le système immunitaire, nous avons fondé la société Morphosys. C’est alors que la question suivante s’est posée: est-ce que nous pouvons utiliser d’autres molécules de protéines et résoudre ainsi de nouveaux problèmes? C’est comme cela qu'ont été conçues les Designed Ankyrin Repeat Proteins (DARPins) et une deuxième entreprise, Molecular Partners à Schlieren. Le défi suivant consistait à stabiliser les récepteurs grâce à l’ingénierie des protéines afin de pouvoir développer plus efficacement des médicaments pour ces points sensibles. En raison de ces recherches, nous avons créé une troisième société, G7 Therapeutics.

Qui a respectivement motivé ces créations d’entreprises?

Pour la première entreprise, ce sont mes collègues chercheurs. J’étais alors le plus sceptique des trois. Les deux autres sociétés sont des spin-offs classiques de mes doctorants et post-doctorants.

Aujourd’hui, quelle est la situation de ces entreprises?

Morphosys compte actuellement 430 collaborateurs. L’entreprise a récemment fêté son 25ème anniversaire. De plus, nous avons reçu la première autorisation de la FDA pour un anticorps qui est donc désormais disponible sur le marché. Cette société est l’une des rares qui fait encore exactement ce que nous avions écrit à l’époque dans notre business plan et qui connaît toujours le succès. Molecular Partners emploie 130 collaborateurs, avec plusieurs études en phase deux et trois. Tout comme Morphosys, l’entreprise est cotée en bourse. G7 Therapeutics a été rachetée par l’entreprise anglaise Heptares appartenant elle-même à la société japonaise Sosei. En bref, toutes les entreprises vont bien. Pour moi, la fondation en soi ne représente pas une réussite particulière. Ce qui m’intéresse, c’est plutôt que l’entreprise se porte bien et commercialise des médicaments.

Quels sont les changements auxquels vous avez fait face pour les créations d’entreprise au cours des décennies?

L’environnement a totalement changé. En Europe, il y a 25 ans, créer une entreprise de biotechnologie n’allait pas de soi. Pour cela, les gens partaient en Californie. Aux Etats-Unis, lors d’un symposium, j’ai été accueilli en tant que chercheur et fondateur d’entreprise par la phrase: «He is like us». Là-bas, il était normal depuis bien plus longtemps d’être à la fois chercheur et entrepreneur. Chez nous, le scepticisme a désormais disparu et de telles créations d’entreprises sont perçues de manière positive. De plus, il existe désormais une scène «venture capital». Pour être honnête, je dois dire que par rapport aux bailleurs de fonds, il est utile d’avoir déjà fondé une entreprise prospère. Le premier accord est le plus compliqué.

Vous semblez avoir bien réussi en tant que créateur d’entreprise. Est-ce que vous n’avez jamais eu envie d’intégrer l’une de vos sociétés?

Pour moi, il n’a jamais été question de quitter la haute école. C’est un privilège incroyable d’être payé par l’Etat afin de faire des choses un peu folles. J’ai toujours voulu réfléchir au prochain défi au sein de la haute école. Dans ce cadre, ne pas être obligé de justifier des bénéfices trimestriels constitue la seule possibilité d’assurer le progrès. Dans une entreprise qui utilise l’argent des investisseurs pour la recherche, il n’est pas possible de réaliser des projets risqués et longs comme ceux qui m’intéressent. Mais je peux affirmer que grâce aux entreprises qui se basent sur mes recherches, j’ai remboursé mon dividende et créé de nombreux emplois.

Vous continuez donc à vous consacrer à la recherche fondamentale. Est-ce qu’il est possible de pousser celle-ci vers une commercialisation accrue?

Nous avons toujours voulu résoudre des problèmes qui nous semblaient suffisamment importants. A moment donné, dans la recherche, la question qui se pose est de savoir comment l’on utilise les résultats, ce qui en découle. Si nous n’avions pas commercialisé les résultats, les projets se seraient simplement arrêtés alors qu’ils devenaient intéressants. Nous serions restés bloqués à mi-parcours. C’est comparable avec un plan de construction pour un ordinateur que l’on ne construirait pas. En fondant des entreprises, nous voulions nous assurer que les projets continuent.

Dans le cadre de vos recherches, est-ce que vous avez collaboré avec l’industrie?

La collaboration directe entre l’industrie pharmaceutique et notre laboratoire n’a jamais vraiment bien fonctionnée. Les attentes et les horizons temporels sont très différents. Nous développons de nouveaux concepts et de nouvelles idées. Souvent, cela n’est pas compatible avec la recherche pharmaceutique de la grande industrie. Je pense que je ne froisserai personne en affirmant que l’industrie pharmaceutique est très conservatrice. Nous avons certes de nombreux contacts, mais très peu de collaborations. Cependant, les entreprises que nous avons créées travaillent très bien avec l’industrie pharmaceutique.

Quels sont les prochains thèmes auxquels vous allez vous consacrer?

Nous effectuons des recherches sur les virus artificiels qui ne peuvent pas se multiplier. Il faudrait que les virus produisent dans le corps les protéines nécessaires en tant que produits thérapeutiques. Il s’agit d’un sujet tellement éloigné de la mise en œuvre pratique qu’il est uniquement possible dans une haute école. Mais je suis convaincu que cela aurait des conséquences énormes si cela fonctionne. Je ne serais pas tranquille si nous ne tentions pas au moins le coup. Dans mon laboratoire, nous essayons donc une fois de plus de résoudre un problème que la plupart des spécialistes jugent impossible. C’est ce qui nous motive à nous lever le matin. Je veux démontrer que cela est possible malgré tout.

Inscription à l'événement: Andreas Plückthun between basic research and biotech entrepreneurship on 24 April 2018.


A propos d’Andreas Plückthun
Andreas Plückthun est biochimiste et chercheur dans le domaine de l’ingénierie des protéines et de l’évolution dirigée de protéines, en particulier d’anticorps, de molécules synthétiques de liaison et de protéines membranaires. Il est professeur à l’Institut de Biochimie de l’université de Zurich depuis 1993. Il a étudié la chimie à l’université d’Heidelberg et a passé sa thèse à l’université de San Diego en Californie. Il a réalisé son post-doctorat à l’Institut de chimie et de biologique chimique de l’université Harvard. Après son séjour de sept ans aux Etats-Unis, Andreas Plückthun est revenu en Allemagne pour devenir chef de groupe au centre génétique de l’université de Munich et à l’Institut Max-Planck de biochimie à Martinsried. Il est membre de la European Molecular Biology Organization (EMBO) et fait partie de Leopoldina, l’Académie nationale des sciences. Il a reçu de nombreux prix internationaux et a été récompensé en tant que pionnier de l’ingénierie des protéines. Andreas Plückthun est co-fondateur des deux sociétés spin-off Morphosys (actuellement: 400 collaborateurs) et Molecular Partners (actuellement 40 collaborateurs) cotées en bourse.

Interview: Annett Altvater et Stephan Emmerth, BaselArea.swiss

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Meet the BaseLaunch Startups

11.03.2018

Six of the BaseLaunch startups recently started Phase II. They received either grants up to 250,000 Swiss francs or gained free of charge access to BaseLaunch laboratory and office space at the Switzerland Innovation Park Basel Area. Hear what the startups, the BaseLaunch team and selection committee members experienced in the first year. Find out more about what makes BaseLaunch unique.

The BaseLaunch accelerator is now open for applications for the second cycle. Entrepreneurs with a healthcare based project or a game-changing innovation in diagnostics, medtech or related field at the pre-seed or seed funding stage are invited to submit their applications to the program.

Following the application deadline on 14 May, promising projects will be admitted to the accelerator program for a period of 15 months. In phase I, the startups will benefit from the support of industry experts, office- and laboratory space free of charge and access to healthcare partners. After three months, they will be invited to present their idea to the selection committee. They will determine which promising startups will proceed to Phase II that runs for one year.

BaseLaunch is backed by five industry leaders — Johnson & Johnson Innovation, Novartis Venture Fund, Pfizer, Roche and Roivant Sciences. Other public and private partners such as KPMG and Vossius & Partner also support the initiative.

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report Precision Medicine

“Precision medicine is the best opportunity to reconfigure healthcare”

04.12.2017

After 20 years with the pharmaceutical company Eli Lilly, Bernard Munos set out to better understand pharmaceutical innovation – specifically what makes it possible and how to get more of it. Munos is now a Senior Fellow at Faster Cures, a Center of the Milken Institute, and the founder of the consultancy InnoThink, which advises biomedical research organizations on how to become better innovators. He also contributes to Forbes magazine, an American business publication. Munos travelled to Basel in October, on behalf of HKBB and DayOne to participate in the “Powertalk”.

Mr. Munos, precision medicine has been around for a couple of years. These days everybody seems to talk about it. Why is that?

Bernard Munos: The healthcare system is increasingly torn apart by powerful forces. On one hand, science is delivering amazing things such as protein therapeutics (peptides, monoclonal antibodies); cellular therapies (CAR-T); gene editing (CRISPR); and a growing array of technologies based on a molecular understanding of diseases. The only problem is that this is very expensive. In addition, the population is aging, and older people tend to get diseases that are costlier to treat. The result is nearly infinite demand for costly care, which is clashing with the limited resources available to fund it. But, as it turns out, precision medicine is the most promising opportunity to change the economics of pharmaceutical R&D, reconfigure healthcare, and deliver affordable care to all.

In other words: the current system is not built to distribute the benefits of the new technologies?

For decades, R&D was much simpler: We took a disease that we typically did not fully understand, threw a bunch of compounds at it and saw if something would work. If it did, you had a drug. This was crude, but not a bad strategy since it gave us drugs long before we understood the diseases they treated. Sometimes, however, it does not work. For example, we have thrown over 350 compounds at Alzheimer’s, but none has worked, and we still do not know what causes the disease. There’s got to be a better way, and that is precision medicine.

What will change with precision medicine?

Once we understand how diseases work, our capabilities are so powerful that we can often design a disease modifying molecule literally within months. Precision medicine, along with the technologies that enable it, will give us the insights we need to develop those drugs. But it translates into a smarter – and ultimately cheaper –  way to do science and develop drugs –which is why it will prevail.

What do we need to establish to get precision medicine taking up more speed?

According to the Food and Drug Administration, the number one impediment to innovation is the lack of natural histories for most diseases. This means that we do not have baseline data that describes the course of the disease, and therefore we cannot measure the improvement that a therapy would bring. It really limits our ability to innovate. Many diseases progress quietly for many years before they are diagnosed. Take Alzheimer’s or pancreatic cancer: by the time they show symptoms, it is too late for an intervention. Precision medicine will change that by collecting data while the diseases progress but the patients are asymptomatic. This will advance disease discovery and give us the knowledge we need to develop better therapies. Much of this will be enabled by new and inexpensive data-capture technologies such as biosensors, apps and other plug-in devices that are advancing very rapidly.

But first of all this means new investments – who is going to pay for all this?

At the moment, public companies spend US$110 billion per year on clinical research, much of which goes to collect data. This is an enormous amount of money, and companies gather indeed vast quantities of data, but they are limited in scope and often of mediocre quality. In 2014, the company Medidata Solutions ran an experiment to test the capabilities of biosensors. They assembled a couple hundred patients and equipped them with a few low-cost biosensors such as activity trackers and heart monitors. Over a couple of months, they collected up to 18 million data points per patient and per day. That data was later reviewed by regulators and declared to be “FDA-compliant”. One key point, however, is that its collection cost was trivial. Other evidence suggests that, by redesigning trials to leverage digital technologies, we can cut down the cost of data collection by as much as 80 percent. This is big enough to change the economics of clinical research, but it does more. It also enables better research. Today, drug trials focus on homogenous patient populations, because one needs to minimize the sources of variance. But the result is trials that do not represent very well the populations that we want to treat. Biosensors, on the other hand, can collect lots of data on larger populations, and statistical significance is usually not an issue. It is also high-frequency longitudinal data which gives us a much better picture of what happens to patients.

How will this change medicine?

Today, when someone comes down with Alzheimer’s, we don’t know when it started, or why, and therefore have no way to intervene on the course of the disease before it is too late. If we had data on pre-symptomatic patients, scientists could look back and pinpoint when the disease might have started and how it progressed. With such information, we could design better drugs and intervene earlier when the prognosis is better and treatment costs cheaper. It could potentially move medicine from treatment to prevention, but implementing it won’t be easy. Our whole healthcare system is designed to treat not prevent. Changing it will require a lot of retraining, but it’s the way to go.

Crucial will be the question who owns the data and who will have access to the data?

A key requirement of precision medicine is that data needs to be connected. It will be scattered over hundreds of databases, but they need to be interfaced so that they can easily be searched. Some of the data will be public, but much of them will be collected and controlled by the patients themselves. A majority of patients has signaled a willingness to share their data for legitimate research purposes, but whoever controls data will also control innovation. Patients hold values that are dear to them – such as transparency, openness, and affordability – and they will likely expect the recipients of their data to comply with these values. This will be a big change for the culture of R&D and will have significant consequences for the design of clinical research.

This will change the Value Chain – who will win, who will loose?

Precision medicine will bring some desirable changes: Historically pharmaceutical companies have generated their own data and competed on the basis on such proprietary data. Increasingly, however, data will become a commodity. For instance, the data from the “All-of-Us” million patient cohort that the U.S. National Institutes of Health is assembling will be in public access. There are numerous other large patient cohorts around the world that are being created and whose data will also be public. This will change the basis of competition. Scientists will increasingly work from shared, public data, and their performance will depend upon their ability to extract superior knowledge from the same data used by their peers

What does this mean for the Basel Life Science Cluster?

Big corporations struggle to generate enough internal innovation. The bigger they get, the greater the bureaucracy and the more regimented they become. This creates a climate that is less hospitable to innovation precisely at a time when large companies need more of it. To sustain revenue, they must access a source of external innovation that can supplement their own.  Relying on licensing, mergers or acquisitions does not work well, as companies seldom find what they want to buy at a price they are willing to pay. Innovation hubs such as BaselLaunch or DayOne are a better solution. They allow the local community to create shared infrastructure – such as incubators and support services – that can become a global magnet for entrepreneurs. They also give the local large companies an opportunity to mentor the startups and offer scientific support. For them, it is a way to seed the local ecosystem with innovation that they can harvest later on.  Basel is especially suited for this because innovation tends to blossom where cultures overlap. This has been a factor in the city’s past success, and it is an asset that can be leveraged again.

Do we have enough data scientists?

You certainly have them in Switzerland. Data sciences have long been a strength of Swiss education. It goes hand-in-hand with engineering, physics and other sciences in which Switzerland excels. It is also an important advantage since there is an acute shortage of data scientists around the world. Processing the big data flows discussed earlier requires much larger numbers of data scientists that we are currently training. In America, this has been identified as a critical workforce issue. Switzerland is in a stronger position.

Would an open data platform work like a catalyst?

Scientists flock to data. In all scientific projects, a huge amount of resources – as much as 80% – is spent on data collection and cleanup, which are seldom the most interesting parts. If Basel can offer rich data that is already curated, scientists will be able to accomplish much more while focusing on the part of their work where they really add value. Having data in open free access will also help attract researchers from other disciplines who currently do not engage in biomedical research – such as mathematicians and artificial intelligence experts. Such cross-pollination is a powerful catalyst of innovation.

About Bernard Munos
Munos is a Senior Fellow at FasterCures, a center of the Milken Institute, and the founder of InnoThink, a consultancy for biomedical research organizations. He regularly contributes to Forbes and is a board member and independent non-executive director of innovative healthcare companies.

Interview: Thomas Brenzikofer, Annett Altvater

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"I want to turn innovative research into new drugs"

04.07.2017

Each year some 250,000 patients develop a type of cancer because of faulty communication between cells. This malfunction occurs in what is known as the NOTCH signal path. There are currently no effective treatments – but this is set to change. Cellestia Biotech AG is developing an innovative drug against this type of cancer by using a novel active ingredient that selectively attacks the malfunctioning cell communication. The drug could be used to treat leukaemia, lymphomas and solid tumours such as breast cancer.

In 2014 Professor Freddy Radtke and Dr Rajwinder Lehal, who had dealt with this subject in his dissertation, founded the company Cellestia Biotech AG. In 2015, an experienced team of pharmacology and oncology development specialists led by Michael Bauer came on board, investing in Cellestia as co-founders. Bauer and his team had previously spent several years examining various projects in an effort to help shape the development of such a start-up company. We spoke with him about the risks and implications of founding a company.

Interview: Stephan Emmerth

Mr Bauer, how long did you have to look before you found a project you wanted to invest?

Michael Bauer: Over the course of many years and alongside my regular jobs, I and my colleagues examined, evaluated and rejected a number of projects – sometimes more intensively, sometimes less. Some of the projects were great, some being unbelievably innovative. However, something always led us not to pursue a project in the end.

The search did not just cost you a lot of time, but also a lot of money as you have to conduct due diligence every time.

We of course had to put effort into the search. You could say that we identified, examined and evaluated projects acting similar to a small venture fund. Thanks to the make-up of our team, we were able to undertake many of the tasks ourselves, at times bringing in experts. There were many instances when specialists from our network assisted us. There was a considerable amount of good will. To some extent we footed the bill ourselves.

Why did this not work out before Cellestia?

A number of conditions have to be met. The basis is of course excellent, innovative research results protected by patents. Also important are ownership rights to the inventions and reasonable licencing terms. Finally, there has to be agreement on the expectations of the people involved in the project. We have experienced pretty much everything. Many times it emerged over the course of the investigation that, for example, the research data was not quite so convincing as had initially been presented. Or the expectations with respect to the licencing conditions were too far apart. In one project, they wanted to sell us patents that had expired. It often happens that the scientists have unrealistic ideas about the value of their project. One retired professor who had tried in vain for many years to finance his company expected us to try for five per cent of the shares. This is of course not the basis for a partnership.

Juggling research and entrepreneurship is a big challenge, isn’t it?

It is necessary to develop an understanding of the relations and contributions of the various partners involved in such a project, each of who have very different personal risks. On the one hand, there is some 20 years of basic research behind Cellestia, 11 of which were at the EPFL. Rajwinder Lehal has been working concretely on this project for the past nine years, initially as part of his dissertation, then as a post-doc and since 2014 as Chief Scientific Officer. We respect this history from the management team and are happy to have access to the resulting knowledge. At the same time, the inventor’s side has to have regard for the entire expenditure: some five million of public funds were invested over the years at the EPFL. However, it could take hundreds of millions until a product comes onto the market. Moreover, the path from the first successful experiment in lab animals until a drug is approved for human use is long. Altogether, the cost of research could be marginal in comparison to the development and marketing, amounting to only a few per cent. And the development costs are paid for by the investors, who need the investment to pay off. All of these factors have to be considered and respected in a partnership. This worked with our team.

You have many years of industrial experience. What attracted you to the entrepreneurship?

The challenge of turning ground breaking inventions into products attracted me. I consider myself a product developer and had wanted to start a company even as a student. Looking back, I have to say that I am lucky to have gained nearly 20 years of professional experience in product development as it is important to be able to understand and appreciate just how complex the challenges are in product development in life sciences and pharma. This wealth of experience also helps you understand where your own knowledge ends and when experts have to be brought on board to be able to successfully advance a project or a company.

What was the incubation from first contact until you joined as co-founder at Cellestia like?

The current Chief Scientific Officer, Rajwinder Lehal, and I had been in regular contact with each other for a number of years. At that time, however, the project was not advanced enough to establish a company. Initially, Professor Radtke, Rajwinder Lehal and Maximilien Murone founded Cellestia in 2014. We met a few times in summer 2015 with the Lausanne research and founder team at i-net, the predecessor of BaselArea.swiss. Things moved quickly from there. In just a few meetings, we were able to evaluate the project and develop a good personal understanding, which for me and my partners was very important if we were to invest in Cellestia. We could agree on matters quickly, more or less by handshake. Then came the necessary contracts and in November we were already listed in the commercial register. Our lawyer and co-founder Ralf Rosenow saw to the formalities. We decided to move the headquarters from Lausanne to Basel but to leave the research activities in Lausanne, resulting in a sort of transcantonal partnership.

Why move the headquarters to Basel?

For us, the most important argument in favour of Basel was access to talent and resources for product development, resulting from the proximity to leading pharmaceutical companies such as Novartis, Roche, Actelion and many others. Such access to experienced development specialists is more difficult in Lausanne. In addition, our co-founder Roger Meier and other colleagues already have an active investor network in Basel with an affinity to the sector and Basel itself. We did not have such access in Zurich or Geneva at the beginning. I personally also like the quality of work and life in Basel. The city is of a manageable size yet international, with diverse cultural offerings. Furthermore, the Basel airport has excellent connections – you are in the middle of Europe and in just one to two hours you’re practically anywhere Europe, be it London, Berlin or Barcelona. Lausanne, on the other hand, has in its favour the outstanding academic environment with the EPFL and the Swiss Institute for Experimental Cancer Research. Here, too, there is an excellent environment for start-ups, but in our opinion more toward engineering and technical disciplines or medicine technology. Many companies are founded each year at the EPFL and the innovation potential is enormous, but Cellestia is the first company founded at the EPFL that seeks to bring a drug to clinical development. We are happy to be able to combine the positive elements of both regions via what is now an established approach with two locations.

Which pre-conditions were decisive enough that you ended up collaborating and founding the company?

Actually, everything was right from the very beginning. First of all, the personal atmosphere between the people involved has to be right. This was also the basis in coming to a fair agreement for all co-founders with respect to understanding the evaluation and allocating the respective shares in the company at the time it was founded. On the other hand, it was of course crucial that the substantive examination of the project – as concerns both the scientific basis and the quality of the data – and the examination of the patent as well as license conditions of the EPFL were positive. Also important to us was that the risk profile is manageable, i.e. there is a good balance between innovation and reference to the research already carried out.

How will Cellestia develop further operationally?

Cellestia already has a long history, starting with the research activities at the EPFL. When the management team was expanded in 2015, other co-founders joined at the same time that I did: Dirk Weber as Chief Medical Officer, as well as the already mentioned co-founders Ralf Rosenow and Roger Meier. Cellestia now has six employees. Then there are the numerous service and consulting mandates, which complement our internal resources as needed. If you take into consideration external services, I reckon there are now well over 100 people involved in Cellestia. We expect that we will continue to grow in the direction of clinical development as our first project progresses and further expand the team. Moreover, we would like to develop additional products in our pipeline as soon as possible. This will definitely require additional financial resources. The Board of Directors will also develop further, expanding and adapting with each financing round in order to properly represent new investors. Research work is increasingly being carried out by external services providers, and at the same time continuing in the laboratory of Professor Freddy Radtke at the EPFL. We are currently setting up new framework agreements with the EPFL concerning the further use of their infrastructure. The flexibility there is very helpful for us.

What are the next milestones?

A key milestone is the treatment of the first cancer patients. We hope to be able to treat the first patients in October.

How are the clinical studies organised?

The course of a clinical trial for new drugs is strictly regulated. In the Phase I study, the compatibility of the active ingredient is first examined. This is when we treat patients who are suffering from a form of cancer in which NOTCH most likely plays a role. In the following Phase II study, the efficacy of our drug is researched in different types of cancer. This is when we select patients in whom activation of the NOTCH signal path is detected with a Cellestia diagnostic method. The therapeutic benefit for these patients is therefore very likely.

Have there been any surprises so far?

No, not really, because we have considered everything. Or yes, but pleasant surprises: due to the considerable amount of preparatory work, we were already quite certain with respect to the effect mechanism. It has now finally been possible to detect the precise binding mechanism of the drug, which confirmed all former studies. This is also the basis for significantly expanding the programme. We can now build a new platform on whose basis we can generate new drugs for new indications. In addition, it was not that easy to manufacture the drug in large quantities and in a high quality. Innovative steps were needed, which ultimately leads to a patent.

What do you have in mind for the next five years?

We are very optimistic about Cellestia’s prospects for success and are planning the next couple of years in detail. We of course also have a plan for the overall development over the next five years, but as experience shows, such plans always change with the results obtained. This is also the fascination and challenge in medication development – it does not allow you to plan everything in detail, and you have to respond flexibly to new results. This also applies to possible setbacks, of course. It is important to have sufficient reserves to deal with these and resolve them. Thanks to the successful financing rounds that we could close in January 2017, we are in a position to begin with Phase I while at the same time pursue further financing.

Who has invested in Cellestia so far?

The first investors after the deposit of the initial capital were predominantly many of our advisors, i.e. experts who are familiar with the sector as well as private people involved in life sciences and the pharma sector as investors. Around one-third of the shareholders are experts from the pharma and life sciences setting. Over the course of the Series A, B and C financing rounds, larger investments from family offices also came. The first institutional investor, the PPF Group, invested after its own, extensive due diligence that was conducted by experts from Sotio. So far, we’ve been able to mobilise a total of CHF 8 million to drive product development at Cellestia. In preparation of the next financing round, we are in talks with private investors, venture funds and pharmaceutical companies. We are confident that we will be able to win good partners for Cellestia’s next phase. The right combination of partnerships and financing is important. We need strong partners on board to give patients access to our medications quickly.


About
Michael Bauer (born 1966) has been CEO at Cellestia since November 2015. He studied chemistry at the University of Hamburg and completed his doctoral in biotechology from 1994 to 1997 at the Hamburg-Harburg University of Technology. After working in metabolic research at Zeneca in England, he moved to Syngenta in Basel in 2001 where he worked as Global Regulatory Affairs Manager in project and portfolio management. From 2007 to 2009 he was a project leader at Arpida, a biotech firm in the field of antibiotics development. From 2009 to 2012 he was a Global Program Manager at Novartis where he led global development projects in the field of oncology and brought a range of products to clinical development. From 2012 to 2015 he was the Head of Clinical Development at Polyphor.

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A molecular assembly line to cure the body

08.06.2017

Imagine that certain forms of blindness could be cured. Or imagine that the body itself could produce a cure for some of its own diseases. These may be just some of the results of the National Centre of Competence in Research Molecular Systems Engineering (NCCR MSE). Its long-term goals are to create molecular systems and factories for the production of high added-value chemicals and develop cellular systems for new applications in medical diagnostics, therapy and treatment. Director Thomas Ward is aiming high: He wants to make Basel the leading hub for the next European flagship project. At stake: one billion euro.

Interview: Ralf Dümpelmann

Thomas Ward, you are the director of the NCCR MSE. How did you end up in this position?

Thomas Ward: During my work at the University of Neuchâtel we became curious about artificial metalloenzymes. For instance, we could take ruthenium ion that nature does not have much of at its disposal, and incorporate it in a protein to yield an artificial metalloenzyme. Pursuing this curiosity driven pathway, my group became more and more interested in biological questions. Ultimately I wanted to collaborate with molecular biologists – and this is one of the main reasons why I moved to Basel. When I arrived here nine years ago, the ETH Department of Biosystems Science and Engineering (D-BSSE) had just moved to Basel. That led professor Wolfgang Meier, then head of the Department of Chemistry at our university, to initiate talks with the D-BSSE which were very productive. In the end, he and co-director professor Daniel Müller set out for a National Centre of Competence and Research that ultimately got funded by the Swiss National Science Foundation (SNSF).

What was the goal when starting the NCCR?

Wolfgang Meier and Daniel Müller saw the opportunity to start a collaboration between biologists who relied quite heavily on chemistry and chemists who can provide the required chemical building blocks to address challenging biological questions. This is scientifically a very unique match. In my view this is also reflected in the most important aspect in the title of our NCCR – molecular systems engineering – namely the systems aspect.

Do you build artificial biological systems with the help of chemistry?

At the end of the road, we want to reproduce the properties and the complexity of a living system. There are two ways to get there. The chemical way is to take a compartment, put objects inside one by one and see what evolves. That is the bottom-up approach. On the other hand, a biologist takes a complex system and knocks out components, one at a time. In doing so, biologists focus on computing a system. And they are doing this very well. They can control things, even without fully understanding the molecular details of such systems. These two approaches meet at some point, and that is where our NCCR comes into play.

What could a potential end result look like? A small golem?

If you take the definition of what is life, there are a few features that we are definitely not trying to mimic. We are rather focusing on an artificial organelle, something that you could introduce into a living system and which would work in a living system, but which does not have all the features of a living system itself. I like to call such components molecular prostheses. It is like an artificial Lego block that fits into living systems. There we are already quite advanced.

Can you explain how the work of the NCCR is structured?

The network is planned to work over twelve years, split in three phases. There are roughly 30 groups associated with this NRCC, with some 20 in Basel. When there is somebody outside of Basel who has a competence that we need, they can be integrated to the network. That might be people in the Paul Scherrer Institute or at the University of Bern, for instance.
We are now approaching the end of the first phase of four years. The first step for us as chemists is to synthesise and assemble molecules into modules, an assembly of several molecules. For example, Sven Panke at the D-BSSE and myself synthesise artificial enzymes. Daniel Müller of the D-BSSE on the other hand manipulates pore proteins which allow to control the trafficking of substrates and products in and out of a cell. The goal is assemble an artificial organelle containing two or three enzymes and to introduce this prosthesis inside a cell. With that we can complement the natural metabolism of a cell with an artificial metabolism to produce new chemicals. At the end of the first phase, we ideally want to have solved the module’s problem. In the second and third phase, we can then focus on creating molecular factories and cellular systems.
Ultimately, a chemical factory could produce something that could be useful and a cellular system could be used to cure a disease. For both of these goals, you need a molecular assembly line, much in the spirit of what Henry Ford developed in the early twentieth Century, but at a molecular scale.

Do you already get a stable system out of these assembly lines?

Yes. The question is, however, how stable and for how long. We have systems that function in a cell for two weeks. Whether this is enough to cure a disease remains to be demonstrated.

What benefits may come out of it?

Our aim is to change the way biology and chemistry work in the long term. It is a risky strategy, but with a potentially high payoff.

What would be the high payoff?

You put a molecular or cellular system in the body and it treats or cures a disease.

When will that be feasible?

There are two systems, which are already very well advanced. Both were initiated and funded by the NCCR. Botond Roska of the Friedrich Miescher Institute for Biomedical Research has developed a system that can be injected into the eye to regain vision. This system will enter clinical trials in Winter 2017. It is based on genetic engineering, where you have to inject DNA so that your eye starts to produce pigments again. The other one is aimed at curing diabetes. Your fat cells are re-programmed into cells that are capable of producing insulin. They are then injected into your body and allow you to autonomously produce insulin when the body needs it.

Will these ideas be used in start-ups?

Yes. There are already two start-ups that were created in the past three years. The diabetes treatment is also seriously being looked at for a start-up. The SNSF wants to see things like that. It wants us to bring our research to an advanced stage.

You are organising the International Conference on Molecular Systems Engineering in Basel at the end of August. What is its main goal?

It is a challenge to organise such a conference because people who attend conferences like to talk to specialists in their fields. In our case, we want to apply our approach to a number of different fields. There will be outstanding speakers, but we have to convince people that it is worth looking at the subject from a broader perspective. The good news is that there are similar projects in Europe, in the Netherlands and in Germany. We will have a pre-conference, where graduate students from these other projects can exchange experience and ideas with students from the NCCR.

Is the conference a step to the European level?

Four years ago, the EU funded so called flagship projects. One of them was the Graphene project in Manchester, the other one the Human Brain project at the EPFL in Lausanne. These flagships have a budget of a billion euro. It seems that Europe will have a second round of such flagship projects in a few years. Our aim is to apply for the funding together with our partners in Germany and the Netherlands which would ensure the development of molecular systems engineering at a European level in the future.

In unique events the conference combines art and research. What is the idea behind this special mix?

It is about communication and ethics. We asked ourselves how we can talk about our research as it is quite complex for lay people to understand. One answer is to interact closely with artists and see if they can show their interpretation of what we do, and hopefully this would speak more to the public. We worked with artists hoping that they might rise interest in our research. Furthermore we can engage the public in a dialogue about ethical questions.

When will this dialogue start?

At our conference the argovia philharmonic will present a composition based on illustrations and videos we have provided them with. On the same day, we will also have a public ethics debate. We have brought in an editor of “Science” who will animate the debate and there will be three people debating. We hope one of them will be a bioethics officer of the Pontifical Academy for Life, the two others will be scientists.

What was for you the scientifically most exciting aspect of this NCCR?

When we started, we had a very broad approach and we had quite a number of curiosity-driven research projects. Without it, we would not have come as far as we did in these three years. For the second phase – we have just submitted the pre-proposal – we are much more focused.

What do you hope to achieve at the end of the NCCR?

If we only get one product in use this would already be a very nice achievement. Imagine, for example, that we could say: This NCCR has cured some forms of blindness.

About:
Professor Thomas Ward, born in 1964 in Fribourg, is the director of the NCCR Molecular Systems Engineering. He heads the Ward Group at the Department of Chemistry of the University of Basel. The group’s research focuses on the exploitation of proteins as a host for organometallic moieties with applications in catalysis as well as in nano-biotechnology.
Ward studied organic chemistry at the University of Fribourg. He wrote his PhD thesis at ETH Zurich. He did a first postdoc with Roald Hoffmann at Cornell University in theory and then a second postdoc in Lausanne. He was then awarded an A. Werner Fellowship and moved to Bern where he obtained his habilitation. He moved to Neuchâtel in 2000 and to Basel in 2008. He was awarded a prestigious ERC advanced grant in 2016 and the 2017 Royal Society of Chemistry award in Bioinorganic chemistry.

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“I see a very innovation-friendly climate in Basel”

12.04.2017

It all began with research resources that were a quarter of a century old. Simon Ittig and his colleagues at the Biozentrum of the University of Basel turned these into a research project – and eventually a start-up. T3 Pharmaceuticals develops new therapies to treat solid tumours.

How did T3 Pharma come about?

Simon Ittig: I completed my doctorate at the Biozentum in Professor Guy Cornelis’ group, which dealt primarily with a secretion system of bacteria. Bacteria require these needles to inject proteins into cells and establish their pathogenesis. My doctoral supervisor discovered this mechanism 25 years ago and had researched it ever since. When I completed my doctorate in 2012 and Professor Cornelis retired, I was able to take over many resources such as bacterial strains and study protocols. As a postdoc in another group at the Biozentrum, I dealt with the question of how proteins can be transported rapidly into cells. This brought me back to my collection of bacterial strains, as they are by nature exactly the same. In a short time, I succeeded in showing that such a protein transport does in fact work – and rapidly, efficiently and synchronously. This potential enthralled my research colleagues and me.

What precisely can this technology be used for?

If you have bacteria that transport specific, for example human, proteins into cells, then you can stimulate these cells as you like. It has long been known that bacteria migrate to solid tumours. Accordingly, we focused on the field of solid tumour oncology and could achieve impressive results in a surprisingly short amount of time. We now have bacteria that grow specifically in a tumour over an extended period of time. We can also now program these in such a way that they produce certain active ingredients and pass them into the cells – precisely to where these substances can take effect. Our technology is very stable.

Was it obvious to you that you could go ahead and start a company with this idea?

Yes, this idea came relatively early. We received the first financial support from CTI, the Cancer League and smaller foundations when we were still just academic researchers. It was already clear then that we wanted to become self-employed with our protein transport technology. Founding our own company was even one of the conditions for further research funding from CTI. The Biozentrum supported us in many ways when we were spinning off. As before, the patents belong to the university, but we have an exclusive global license.

How did you finance T3 Pharma?

In the beginning and also subsequently we received substantial amounts of research funding. However, the funds are generally restricted to salaries and materials. Foundations mainly want to finance the actual research work. At some point you reach a limit, which is why we began to actively look for investors for our company.

With great success. What played a decisive role?

First of all, you have to have the right business idea. Second, you need a good amount of mutual trust. The whole set up should be able to accompany the company for several years. If every couple of years you need a few months to secure the next financing round, then this ties up too many resources, creates a lot of uncertainty and distracts from your research activities. For this reason, we looked – and found – investors who had the financial opportunities and necessary understanding, who believe in us and are ready to go the distance with us.

So were you in a privileged position where you could also turn investments down?

Maybe. I’m convinced that you shouldn’t accept every offer if you don’t have to. We carefully examine the conditions connected to the financing and also want to get a sense of the investors’ intentions. It’s also recommended that you keep your options open. If you become content with something too early, it can become very expensive later on.

You have received over 2 million francs from foundations. Is this unusually large for a start-up?

The effort for such financing is of course also very high, especially at the beginning when you can’t yet show proof of your achievements or have yet to receive any research grants. It’s crucial to bring experienced people on board at an early stage. This gives the foundations the necessary certainty when it comes to the project’s feasibility. It’s also important to appreciate smaller amounts. I’m also very grateful that I could learn a lot about the art of writing applications from an experienced and successful scientist, Professor Nigg. With Prof Nigg from the Biozentrum and Prof Christofori from the Department of Biomedicine, we had formed a professional and interdisciplinary consortium from early on. Without these two experienced professors our company wouldn’t exist in its current form.

How high then was the success rate?

I would estimate that half of our requests have been met with a positive result until now.

You’ve come far with this foundation funding, but you’re taking the next steps with the support of private investors. Is this better than turning to venture capital companies?

We of course looked at both alternatives. Private and institutional investors are not mutually exclusive. But we prefer private people because they are generally alone or in small committees and can decide quickly if they want to invest or not. A second point: it’s also important to me personally that we develop an idea together of the next few years and work towards these goals. The interactions, the shared vision and the sense of similar values bring a great amount of pleasure and confidence. It just has to be ‘right’, professional and personal.

How do you go about finding private investors?

Actually, this only goes via a good network and our experienced consultants. In contrast to venture capital firms, private investors tend to remain discretely in the background. It’s therefore important to think early on about the positioning of your own company, the team and its technology. A well-planned communication also helps. Once the ideas are known, it’s easier to get in touch with the right people. If you win someone over in a discussion, there’s a good chance that a private investor will get involved.

What are your next steps?

The financing of T3 Pharm is secured for the time being. We can therefore concentrate on our research and then validate our technology and prepare for preclinical development. As CEO, I’m working outside of the laboratory for the time being while my four colleagues are focussing fully on the research.

What is your long-term vision?

We want to bring our technology for use in patients. This is the major driver in our day-to-day work. How and when we will achieve this goal, I still can’t say today. And also whether or not T3 Pharma will still be an independent company. Who knows what the future holds. We’re therefore open and focused first and foremost on our research.

How do you see the local ecosystem for young entrepreneurs?

We have a good connection to the university and appreciate the open doors. If you trust people and approach them, you receive a lot of support. I see a very innovation-friendly climate in Basel. Of course the large life science cluster creates an incredibly positive environment for start-ups like us. And how BaselArea.swiss promotes innovation also helps in an uncomplicated way when it comes to meeting the right people.

And yet when it comes to start-ups, Basel lags behind other places. What needs to be done?

Nothing works without self-initiative and perseverance. If you have both, you’ll find the best conditions here in Basel and Switzerland. If I had one wish, it would be to more strongly institutionalise the informal exchange at the university. Earlier input from experienced professionals on a start-up idea could help young researchers gather the self-confidence for the next steps and be more successful in presenting their own ideas to a committee. Rejections can be quite discouraging sometimes.

Are there so many ideas that get buried before they’re even given a chance?

Yes, there are, and I find it a real pity. It’s not a matter of course for many people to stand up in front of others and say “I want this, I can do this, and I’ll do it”. Only a few young researchers trust themselves to overcome such a big hurdle and also pursue a project in the face of obstacles. Many talented young scientists remain on the academic track and continue to publish up until the train leaves for a start-up. It would help if they could discuss their ideas informally, without having to shout it from the rooftops. I’m convinced that there would be even more innovative start-ups. Once this hurdle is overcome, you get an unbelievable amount of support even from professors in other fields encouraging you to continue. This is what happened to me.

And was does your doctoral supervisor say about T3?

He’s extremely happy for us. Guy Cornelis also provides us with scientific advice and helps us where he can. The relationship has also since changed and has become very friendly.

About:

Dr Simon Ittig studied biochemistry and biotechnology at the universities of Bern, Vienna and Strasbourg and graduated from the Biozentrum of the University of Basel in microbiology. The start-up T3 Pharmaceuticals grew out of the research project Type 3 Technologies – Bacteria as a versatile tool for protein delivery.

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Roivant Sciences a choisi Bâle pour siège social

19.12.2016

Bâle – Doréanavant, la société biopharmaceutique Roivant Sciences dirigera son activité mondiale à partir de son nouveau siège social de Bâle. Les sociétés affiliées viendront également s’installer à Bâle. BaselArea.swiss accompagnera Roivant et ses partenaires.

BaselArea.swiss a accompagné Roivant et ses partenaires dans l’évaluation et l’implantation du site. L’organisation de promotion économique du nord-ouest de la Suisse se félicite de l’arrivée des nouvelles entreprises dans la région. Elle se réjouit que de telles sociétés aussi passionnantes et au développement rapide aient fait le choix de Bâle pour y établir leurs sièges. « La mission de Roivant est de réduire, au profit des patients, les délais et coûts de mise au point des nouveaux médicaments », a déclaré Vivek Ramaswamy, fondateur du groupe des sociétés Roivant, cité à l’occasion de l’annonce du nouveau siège social. « Nous sommes convaincus que de nous situer au centre des compétences et innovations pharmaceutiques européennes nous permettra d’atteindre cet objectif. » Roivant Sciences est axée sur les phases avancées de mise au point de médicaments. Roivant collabore notamment avec Eisai, GlaxoSmithKline et Takeda Pharmaceuticals. Le développement pharmaceutique de Roivant concerne les domaines de la neurologie, l’oncologie, endocrinologie, la dermatologie et l’hépatologie.

Dans son sillage, Roivant amène des sociétés affiliées qui prévoient également d’établir leur siège à Bâle. Il s’agit notamment d’Axovant Sciences Ltd, est-il annoncé dans le communiqué. Cette société biopharmaceutique est spécialisée dans la phase clinique de médicaments axés sur le traitement de la démence. A Bâle, l’entreprise a l’intention « de développer une organisation totalement intégrée pour gérer les stratégies commerciales et médicales mondiales, qui prendront en charge la fabrication, la chaîne logistique, la propriété intellectuelle et d’autres fonctions d’entreprise », a ajouté Mark Altmeyer, président et directeur commercial en chef d’Axovant Sciences, cité dans le communiqué. « Notre présence à Bâle nous donnera accès à une réserve de talents hautement qualifiés, essentiels à notre futur succès.» hs

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Dr App – Digital transformation in the life sciences

30.11.2016

The future belongs to data-driven forms of therapy. The Basel region is taking up this challenge and investing in so-called precision medicine.
An article by Fabian Streiff* and Thomas Brenzikofer, which first appeared on Friday, 14 October 2016, in the NZZ supplement on the Swiss Innovation Forum.

So now the life sciences as well: Google, Apple and other technology giants have discovered the healthcare market and are bringing not only their IT expertise to the sector, but also many billions of dollars in venture capital. Completely new, data-driven, personalized forms of therapy – in short: precision medicine – promise to turn the healthcare sector on its head. And where there is change, there is a lot to be gained. At least from the investor’s point of view.

From the Big Pharma perspective, things look rather different. There is quite a lot at stake for this industry. According to Frank Kumli from Ernst & Young, the entry hurdles have been relatively high until now: “We operate in a highly regulated market, where it takes longer for innovations to be accepted and become established.” But Kumli, too, is convinced that the direction of travel has been set and digitalization is forging ahead. But he sees more opportunities than risks: Switzerland - and Basel in particular - is outstandingly well-positioned to play a leading role here. With the University of Basel, the Department of Biosystems Science and Engineering ETH, the University of Applied Sciences Northwest Switzerland, the FMI and the University Hospital Basel, the region offers enormous strength in research. It also covers the entire value chain, from basic research, applied research and development, production, marketing and distribution to regulatory affairs and corresponding IT expertise. The most important drivers of digital transformation towards precision medicine include digital tools that allow real-time monitoring of patients – so-called feedback loops. The combination of such data with information from clinical trials and genetic analysis is the key to new biomedical insights and hence to innovations.

Standardized nationwide data organization
In rather the same way that the invention of the microscope in the 16th century paved the way to modern medicine, so data and algorithms today provide the basis for offering the potential for much more precise and cheaper medical solutions and treatments for patients in the future. At present, however, the crux of the problem is that the data are scattered over various locations in different formats and mostly in closed systems. This is where the project led by Professor Torsten Schwede at the Swiss Institute of Bioinformatics (SIB) comes into play.

As part of the national initiative entitled Swiss Personalized Health Network, a standardized nationwide data organization is to be set up between university hospitals and universities under centralized management at the Stücki Science Park Basel. Canton Basel-Stadt has already approved start-up funding for the project. The standardization of data structures, semantics and formats for data sharing is likely to substantially enhance the quality and attractiveness of clinical research in Switzerland – both at universities and in industry. There is no lack of interest in conducting research and developing new business ideas on the basis of such clinical data. This was apparent on the occasion of Day One, a workshop event supported by BaselArea.swiss for the promotion of innovation and economic development and organized by the Precision Medicine Group Basel Area during Basel Life Sciences Week.

More than 100 experts attended the event to address future business models. Altogether 14 project and business ideas were considered in greater depth. These ranged from the automation of imaging-based diagnosis through the development of sensors in wearables to smartphone apps for better involvement of patients in the treatment process.

Big Pharma is also engaged
“The diversity of project ideas was astonishing and shows that Switzerland can be a fertile breeding ground for the next innovation step in biomedicine,” Michael Rebhan from Novartis and founding member of the Precision Medicine Group Basel Area says with complete conviction. The precision medicine initiative now aims to build on this: “Despite the innovative strength that we see in the various disciplines, precision medicine overall is making only slow progress. The advances that have been made are still insufficient on the whole, which is why we need to work more closely together and integrate our efforts. A platform is therefore required where experts from different disciplines can get together,” says Peter Groenen from Actelion, likewise a member of Precision Medicine Group Basel.

There is also great interest among industry representatives in an Open Innovation Hub with a Precision Medicine Lab as an integral component. The idea is that it will enable the projects of stakeholders to be driven forward in an open and collaborative environment. In addition, the hub should attract talents and project ideas from outside the Basel region. The novel innovation ecosystem around precision medicine is still in its infancy. In a pilot phase, the functions and dimensions of the precision medicine hub will be specified more precisely based on initial concrete cases, so that the right partners can then be identified for establishing the entire hub.

Leading the digital transformation
The most promising projects will finally be admitted to an accelerator programme, where they will be further expedited and can mature into a company within the existing innovation infrastructures, such as the Basel Incubator, Technologiepark Basel or Switzerland Innovation Park Basel Area.

Conclusion: the Basel region creates the conditions for playing a leading role in helping to shape digital transformation in the life sciences sector and hence further expanding this important industrial sector for Switzerland and preserving the attractiveness of the region for new companies seeking a location to set up business.

* Dr Fabian Streiff is Head of Economic Development with Canton Basel-Stadt

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