Embed Size (px)
Citation preview
Biotechnologyin Bavaria PROFILES
PORTRAITS
PERSPECTIVES
GLOBAL PARTNER
Am BioPark 13 | D-93053 Regensburg | Phone: +49 941 92046-0 | Fax: -24 | [email protected] | www.biopark-regensburg.de
1.8 billion Euro turnover
20.000 employees
55 companies (Life Sciences)
3.980 employees
Cluster BioRegio Regensburg
18.000 sqm area
38 companies, 608 employees.
64 start-ups since 1999
fl exible leasehold concept & single offi ces
direct motorway connection
located on the University Campus
own day-care facility
conference rooms and theatre
BioPark Regensburg
Health Industry of Regensburg
A company of the City of Regensburg
Member of
THE SUCCESSFUL INNOVATION CENTRE MADE IN REGENSBURG
BIOTECHNOLOGY | MEDICAL ENGINEERING | PHARMA | ANALYTICS | HEALTH
The transformation of experimentally based inven-tions and innovations into diagnostic concepts andtherapies are the basis of modern biotechnology.
It is therefore no coincidence that this issuegives adequate space to „industrial“ biotechno-logy, with perspectives on new projects, pro-ducts and procedures.
With regard to the laboratory of the future interms of data availability, increased efficiency andsafety, personalized medicine plays a special role.
The following issues are also shaping the futureof the biotechnology industry:
Where are new developments and trends fromall biotechnology areas accurately portrayed?
Why are young entrepreneurs and companyfounders increasingly locating to theInnovation and Start-Up Centre (IZB)?
What prospects does the „DigiMed“ networkoffer for the medicine of tomorrow?
Who supports and sustainably expedites thetransfer of technology from the laboratory tothe market?
What role does the new, future-oriented net-work „bayresq.net“ play towards a powerful andinnovative life science landscape?
Are genetically modified pigs the last thera-peutic resort for damaged organs?
Modern biotechnology provides strong impul-ses for the economy: See for yourself!
Walter Fürst, Managing Director
This publication is also available online at
www.media-mind.info
Editorial
Biotechnology – added value for society
Imprint:
Publisher: media mind GmbH & Co. KGHans-Bunte-Str. 580992 Munich/GermanyPhone: +49 (0) 89 23 55 57-3Telefax: +49 (0) 89 23 55 57-47E-mail:[email protected]
Managing director: Walter Fürst, Jürgen Bauernschmitt
Design + DTP: Jürgen Bauernschmitt
Prepress: media mind, München
Responsible editor: Ilse Schallwegg
Print: grafik+druck, Munich
Published annually: 1 x annually
© 2019/20 by media mind GmbH & Co. KG, Munich.No part of this publication may be stored, copied orreproduced without prior written permission by the editors.
Biotechnology is a multidisci-plinary science-based technolo-gy and finds its application invarious fields, like medicine,food, agriculture or industrialproduction. Biotechnological processes suchas brewing beer or fermenta-tion have existed for thousandsof years. But only this year, theterm ‚biotechnology‘ celebratesits 100th anniversary.Today, modern biotechnologyprovides a strong impetus forthe economy, the research land-scape and, above all, the healthcare sector. In Germany, wehave produced a respectablenumber of very successful bio-tech companies, such as Qiagen,Evotec, MorphoSys, Miltenyiand many others who have be-come global leaders in their field.This also holds true for Bavaria:one of the four companiesmentioned above is based inthe greater Munich area. In2018, MorphoSys became oneof the few companies to have adual listing on the Frankfurtstock exchange and, more re-cently, the US Nasdaq. Havingraised more than USD 200million with their IPO in NewYork, the company can conti-nue with its clinical develop-ment in late-phase trials.
Besides the many drug develo-ping biotech companies locatedin Bavaria, we can also be proudof the many companies thatsupply the so-called tools forpursuing research – the ‚Toolsfor Life Sciences‘. Many ofthese companies operate glob-ally, and some are even leadersin their field. To achieve this,they had to and must rapidlyadapt to the expectations oftheir customers, e.g., by inte-grating artificial intelligence andimplementing machine learningin the instruments they aredeveloping and bringing to themarket.And now we are witnessinghow the shift from experimen-tally based inventions and inno-vations to the creation of newdiagnostic concepts and thera-pies based on the use of bigdata is – albeit still slowly –taking off. With the help ofDigiMed Bayern, a EUR 22.5million program funded by theState of Bavaria, we have takenthe lead in Germany in thisfield. The data of thousands ofpatients suffering from atheros-clerosis will be collected, analy-zed and interpreted, thus enab-ling physicians to select themost reliable diagnostic tooland best treatment. Though
DigiMed Bayern is currently anacademic project it is clear thatthis academic ‚experimental set-ting‘ will eventually evolve intoan economically driven appli-cation in the industry. I am in no doubt: At this 100-year mark, the transformationin and with biotechnology hasonly just begun. With the bio-tech companies and the scienti-fic landscape of which we canboast in Bavaria and all the part-ners in the Bavarian Biotechno-logy Cluster, I am confidentthat we can add value not onlyto our economy but also to oursociety, while coming closer toour vision: Bavaria – the placefor the medicine of the future.
Sincerely yours
Horst Domdey
PrefaceProf. Horst Domdey
Prof. Dr. Horst DomdeyCEO of BioM Biotech Cluster
Development GmbHand spokesman of the
Bavarian Biotechnology Cluster
Biotechnology is one of the keyfactors in academic and clinicalresearch. Especially in the devel-opment of drugs, cancer, im-mune, cell and gene therapies, ithas become indispensable. At thesame time, the pressure on scien-tists to deliver faster, more re-liable results is increasing. With over 25,000 productsPELOBiotech GmbH is one ofthe leading distributors special-ized in primary, stem cells andcell culture media. Based at theGerman Biotech hotspot Mar-tinsried in Munich area, PELO-Biotech offers everything fromtissue dissociation, 3D technolo-gies to cryopreservation. ”Wewant scientists to be able to focuson their actual research work,“says Dr. Peter Frost, CEO ofPELOBiotech. ”That’s why ourexpertise enables us to offer sim-ple solutions that lead to successquickly and reproducibly. Justgive us a call.“ PELOBiotech also has a longhistory of success in the field of3D models: co-founder Dr. Frosthas already successfully intro-duced several 3D systems to themarket. In addition, PELOBio-tech has access to a worldwidenetwork of competent and inno-vative partners. ”We are involved in several co-operations with companies anduniversities. This enables us tooptimize our products constantly,exceed the highest quality stand-
ards and know where the realchallenges are, in the laboratory,“adds Dr. Lothar Steeb, CSO ofPELOBiotech. He has developeda number of products of PeloBio-tech’s premium brand Cellova-tions. ”Defined media are gettingmore and more attention in lead-ing institutes,“ says Dr. Steeb.Therefore, many cell cuture pro-ducts are also available in GMPquality for clinical applications,but also as equivalent R&D pro-ducts at significantly more favor-able conditions. The advantage isthat customers do not need totest these systems again - savingtime and money. Besides their comprehensiveportfolio PELOBiotech can alsooffer customized cells from raredonors, ”so that scientists canconduct their research targetedand efficient finally again“ says Dr.Frost.
PELOBiotech –Your partner
for cells and media
Genexpression
Be one step ahead - togetherwith competent cell experts
Authors:
PELOBiotech GmbH
Am Klopferspitz 19D-82152 Planegg/MartinsriedPhone: +49(0)89-517 286 59-0Fax: +49(0)89-517 286 59-88E-Mail: [email protected]
Dr. Lothar Steeb
Dr. Peter Frost
Choose from over 25,000 cell relevantproducts. Competent, Simple process-es, Ready-to-use
Cell isolation: highly purified enzymes (colla-genase / dispase) for optimal and standard-ised isolation of various cell types, in particu-lar islet and liver cells.Cell culture: human and animal primary cells,iPS, stem cells, labelled primary and stem cells,"Diseased" cell systems; CITES-compliantmonkey cells; customized cellsCell Culture Media and Reagents: Correspond-ing to Cells, Media animal-free, xeno-free,chemically definedCooling and freezing media: Gold standard,DMSO-containing and DMSO-free, costfriend-ly mediaProducts for Genomics/Proteomics3D Models: 3D co-cultures, hydrogels, scaf-folds and scaffold-free systems for the pro-duction of spheroids and 3D ring structures aswell as ECMs Cell Culture models: angiogenesis, 3D tumorspheroids and 3D liver microtissue and mediaTools: Cytokines, growth factors, antibodiesand assay systems such as MicroMatrix Assay,protein labeling reagents for microscopy,FACS, HTS (TR-FRET).
Follow our blog or on LinkedIn:www.pelobiotech.comhttps://www.linkedin.com/company/pelobiotech-gmbh/
Immunic is a clinical-stage bio-pharmaceutical company develop-ing selective oral therapies aimedat treating chronic inflammatoryand autoimmune diseases, includ-ing ulcerative colitis, Crohn‘s di-sease, relapsing-remitting multi-ple sclerosis, and psoriasis. TheCompany‘s development pipelineconsists of three small moleculeproducts: IMU-838 is a selectiveimmune modulator that inhibitsthe intracellular metabolism of ac-tivated immune cells by blockingthe enzyme DHODH; IMU-935is an inverse agonist of the tran-scription factor RORγt; andIMU-856 targets the restorationof the intestinal barrier functionby inhibiting a new and yet undi-sclosed target. In November
2018, Japanese pharma companyDaiichi Sankyo granted Immunican exclusive global option to li-cense IMU-856 and related mo-lecules.Immunic‘s lead development pro-gram, IMU-838, is in phase 2 cli-nical development for ulcerativecolitis and relapsing-remittingmultiple sclerosis, with an addi-tional phase 2 trial in Crohn‘s
disease planned for 2019. Aninvestigator-sponsored proof-of-concept clinical trial for IMU-838in primary sclerosing cholangitisis planned to start at the MayoClinic during summer 2019.Immunic AG was founded in2016 with headquarters in Pla-negg-Martinsried, Germany. SinceApril 2019, the company has beenoperating under the name Immu-nic, Inc. with its registered officein the United States and has beentrading on The Nasdaq StockMarket under the ticker symbol”IMUX.” The listing followed areverse takeover transaction withUS based Vital Therapies, Inc., asannounced in January 2019. Thecompany's research and develop-ment activities continue to be con-ducted in Germany.Concurrent with the closing ofthe transaction, an investor syndi-cate that comprises LSP, OmegaFunds, Fund+, LifeCare Part-ners, Bayern Kapital, High-TechGründerfonds and IBG Beteili-gungsgesellschaft Sachsen-Anhalt,
invested EUR 26.7 million in thecompany. This is expected to besufficient to fund Immunic‘s de-velopment activities into the thirdquarter of 2020. In September 2016,Immunic completed a series A finan-cing round of 31.7 million euros.
Immunic: From Inception
to NASDAQin only 3 Years
Imm
un
ic T
he
rap
eu
tics
Immunic AGAm Klopferspitz 1982152 Planegg-Martinsried/GermanyPhone: +49 89 250079460Fax: +49 89 250079466
[email protected]://www.immunic-therapeutics.com
Dr. Daniel VittCEO and President ofImmunic(Source: Immunic)
Author:Immunic team(Source: Immunic)
Immunic develops best-in-class therapies for the treatment of chronic inflammatory andautoimmune diseases (Source: Immunic)
The ideal of sustainable eco-nomy is an ambitious goal, whichIBB Netzwerk GmbH has beenactively supporting for over adecade now with various instru-ments and measures.
IBB Netzwerk GmbH promotestechnology transfer with allknown means: whether scientificand market-relevant research,the selection of suitable finan-cing sources, support in (grant)applications or networking withsuitable partners for research anddevelopment projects.Through these supporting activi-ties, IBB and its partners have rai-sed over 70 million euros in fun-ding for Bavaria in recent years. Intotal, the network has alreadyacquired over 100 million euros infunding and invested around 270million euros in equity capital. Butthe IBB is also active in a numberof other areas.
‚Motley‘ is the IBB network, in whichbiotechnological companies and re-search institutions are joined by com-panies from the engineering, auto-motive, aerospace, chemical and lubri-cant industries, paper, adhesive and
environmental technologies, nano-biotechnology, bioinformatics and anumber of other sectors.The current111 network partners are locatedmainly in Bavaria, but also in almostall other federal states and in neigh-bouring countries such as France,Austria and the Netherlands.
IBB NETZWERK GMBH:
Driving force of Industrial Biotechnology
Ind
ust
rie
lle
Bio
tech
no
log
ie B
aye
rn N
etz
we
rk G
mb
H
Competence network of theIndustrial Biotechnology
Fig. 1: IBB’s competence network operates in a large number of different industries
The ‚classical‚technology transfer
Developing biobased and at the same time degradable plastics; converting greenhouse gas carb-on dioxide into environmentally friendly products;replacing conventional,petroleum-based goodswith renewable raw materials - what almost sounds like visions of the future are in reality thefields of work of industrial biotechnology. Since 2008, Industrielle Biotechnologie Bayern (IBB)Netzwerk GmbH has been actively committed to the associated change towards a sustainablesociety and greater independence from fossil raw materials. Similar to a catalyst, the network andservice company supports and accelerates technology transfer from laboratory to market.
In the ‚UseCO2‘ network, thename says it all: the harmfulgreenhouse gas carbon dioxide isused as a raw material for variousproducts and energy sources.At ‚MoDiPro‘ digitization is mak-ing its way into biotechnology.There, the network develops digi-tal models for diagnostics and pro-cess optimization.
It is well known that the strengthlies in the community. This iswhy IBB Netzwerk GmbH alsonetworks with domestic and for-eign clusters, networks and asso-ciations within the industry andin related subject areas. Throughthis ‚network of networks‘, thou-sands of relevant groups of peo-ple are reached and the opportu-nity for successful cooperationcan be further increased.
The competence network IBB pre-pares the ground for disruptiveinnovations. If a new thematic focusemerges, IBB Netzwerk GmbHthen establishes so-called ‚sub-net-works‘. These ensure short and effi-cient routes to new projects, pro-ducts and processes for participatingmembers. IBB Netzwerk GmbHcurrently manages four such specia-lized sub-networks in addition to thelarge competence network:
The ‚BioPlastics‘ partners arededicated to the aim of developinginnovative, bio-based and at thesame time biologically degradable,marketable polymers.The ‚Waste2Value‘ network pro-cesses residual and waste materialsfrom various industry sectors andconverts them into higher-valueproducts.
13Industrielle Biotechnologie Bayern Netzwerk GmbH
IBB as partner in twoEuropean projects
In some cases, IBB NetzwerkGmbH also assumes the func-tion of a project partner, e.g.in the two EU-funded projects"SUNLIQUID" (FP7, No.322386) and "LIGNOFLAG"(BBI JU, No. 709606).
The two project consortia areworking on the enzymaticconversion of plant residues,such as straw, to bioethanol.This conversion is to be esta-blished on an industrial scale.In both projects, IBB will beresponsible for disseminatingthe progress achieved atevents and via various mediachannels. It will also acquirefurther stakeholders.
In concrete terms, workshopsfor Romanian farmers whoact as straw suppliers havebeen and are being organized,or parliamentary evenings inBrussels and Berlin with re-levant politicians and stake-holder.
Fig. 2: Geographical distribution of IBB network members
Strength throughstrategic partnerships
Operating consortia -The ‚sub-networks‘ of IBB
Contact:
Industrielle BiotechnologieBayern Netzwerk GmbH
Am Klopferspitz 19D-82152 MartinsriedTel.: +49 89 540 45 47-11Fax: +49 89 540 45 [email protected]
Dipl.-Biol. KatrinHärtling-Tindl
In 1999 BioPark Regensburgkicked into action with its firstbuilding and today with 18,000 m2
is the second biggest center of itstype in Bavaria. Together with itssubsidiary enterprise TechBase,currently over 30,000 m2 of floorspace is available in the technologyand startup centers on the universitycampus in the city on the Danubewith 166,000 inhabitants. For yearsprognostic studies have countedRegensburg as being amongst themost dynamic and fastest growingmunicipalities in Germany. A rea-son for this was and is the consis-tent economic promotion of thecity, which with its active businessand cluster policy has had a signi-ficant influence on the innovativelocation on-site.
“Small but fine” has been the mottotime and again succeeding in bring-ing the decision makers spanningdifferent parties in the cathedral cityto the table and bringing them to-gether on the way towards innova-tive projects. All of the building pro-jects were able to be realized by fun-ding from the EU, FederalGovernment, State of Bavaria, Cityof Regensburg and private equity.As an enterprise of the City ofRegensburg BioPark RegensburgGmbH has been able to constantlyfurther develop its cluster policy inthe Regensburg BioRegion beyondits sole leasing business. It is a regioncertified in East Bavaria with a Silver
Label in accordance with the Euro-pean Cluster Excellence Initiative.In particular the interdisciplinarylinking of biotechnology with otherindustries such as sensory techno-logy has led to new industry bran-ches at the location.
Today over 50 companies withalmost 4,000 employees are active inthe Regensburg BioRegion, a goodten times more than 20 years ago. Inthis period of time we have succes-sfully been able to bring 64 startupcompanies to the Business PlanCompetition for North Bavaria. Todate the companies have acquired661 million €, half as private equityand a quarter of this as venture capi-tal or funding.
The success has many parents. Thelocation is directly on the universitycampus surrounded by two universi-ties and four clinics. The consistentsupport by the City of Regensburgand the State of Bavaria. A self-sup-porting BioPark Regensburg GmbH.The stakeholders on-site from uni-versity and businesses and ofcourse the successful startups withtheir innovative applications.
With our youngest project “Health-care Regensburg – managed by Bio-Park” we are just now expanding thenext interdisciplinary cluster inhealthcare in the region with thesupport of the State of Bavaria. Forthis we have produced a Healthcare
Masterplan which denotes the po-tentials and recommendations foraction for Regensburg and the Regi-on in this field. One point of special-ty is of course digitalization. For the“Digital Health Initiative Regens-burg” we are organizing innovationdays e.g. in caregiving or supportingthe networking of regional stakehol-ders for the exchange of data formultiprofessional and interdiscipli-nary care in the whole of East Ba-varia. With an incubator in the fieldof medical engineering and accelera-tor in the field of healthcare we arepromoting innovation and startups inregional healthcare.
20 Years ofBioParkRegensburg
Bio
Pa
rk R
eg
en
sbu
rg Author:
BioPark Regensburg GmbH
Am BioPark 13D-93053 RegensburgPhone: +49 941 92046-0Fax: +49 941 92046-24E-Mail: [email protected] www.biopark-regensburg.de
Dr. Thomas Diefenthal
CEO
Successfully looking back and looking forward forthe Cluster in East Bavaria
BioM, the network organization ofthe biotechnology industry inMunich and Bavaria, will helpshape tomorrow’s medicine withits latest project „DigiMed Bayern“.At the end of 2018, the DigiMedBayern lighthouse project waslaunched with 22.5 million eurosin funding from the Bavarian StateMinistry of Health and Care(StMGP). The aim of the projectis to integrate P4 medicine (pre-dictive, preventive, personalized,participatory) into clinical routinein the exemplary indication ofatherosclerosis. Finally, diseaserisk prediction, targeted preven-tion, diagnosis and therapy are tobe improved. The scientific leader of DigiMedBayern is Prof. Heribert Schun-kert, Director of the Departmentof Cardiovascular Diseases at theGerman Heart Centre Munich.BioM Biotech Cluster Develop-ment GmbH is responsible formanagement and project coordi-nation. The consortium embracesfurther worldwide leading part-ners from Bavaria such as clinics,patient organizations and researchinstitutions.
One of the most promisingdevelopments in medicine is theintegration and analysis of clinicaldata, research data and patientreal-world information. DigiMedBayern focuses on atherosclerosis,the deadliest disease in industrialcivilizations. The five-year pro-
ject combines comprehensive cli-nical and epidemiological datafrom patients diagnosed withatherosclerotic diseases, such ascoronary heart disease and stroke,and/or with genetic risk factors.This dataset will be further en-riched through state-of-the-artmolecular “multi-omics” charac-terization. For integrative analy-sis of the resulting “big data”, anethically and legally compliant,highly secure and sustainabledigital infrastructure is required.This will be fundamentally de-signed and be implemented witha focus on balancing privacy withsharing of sensitive medical data.Statements were obtained fromthe ethics committee and the sta-te data protection officer early onand will be continuously conside-red throughout the entire pro-ject.The greater vision is to thengenerate real-life improvementsin disease risk prediction, targe-
ted prevention, health care manage-ment, diagnosis and therapy.DigiMed Bayern also wants tocreate an exemplary integrateddigital infrastructure. High-dimensional medical approachesand digital solutions promise topave the way for other similaractivities and finally help shapethe medicine of the future.
The current detailed countrycomparison #SmartHealthSystems,commissioned by the Bertels-mann Foundation, reveals merci-lessly how much Germany lagsbehind in the digitization of thehealth care system. In the study,an overall index was formed fromthe three areas of policy activity,readiness and actual data use. Ofthe 17 countries analyzed, 14 ofwhich are in Europe, Germanyranks second last with only a scoreof 30. Estonia leads with a score
DigiMed Bayernfor the medicine of the future
Dig
iMe
d B
aye
rn
Kick-off meeting of the partners of DigiMed Bayern on October 1, 2018.
Using digital datato combat atherosclerosis
Germany ranks second lastin digitization in health care
already in the conception phaseof the project and addressed thetopic with a public lecture series“DigiMed Bayern Public Semi-nar”. On seven dates fromJanuary to April 2019, ninerenowned pioneers of P4 medi-cine from leading Europeancountries presented their projects.The aim was to determine thecurrent situation, provide orien-tation assistance and internatio-nal networking for players in theBavarian and German healthsystem. A focus was on big datainfrastructures for application-oriented medical research anddevelopment.
Since 1997, BioM is the centralnetwork organization for thebiotechnology sector in Munichand Bavaria, supporting the com-munity in a variety of ways withits extensive network. The non-profit cluster management offerscentralized access. As a centralpoint of contact, BioM connectsBavarian life science companieswith relevant national and inter-national partners. Furthermore,BioM organizes a broad range oftraining courses, events and net-work meetings. Especially forstart-ups the network organiza-tion also provides comprehensiveconsulting services and specia-lized coaching, training and men-toring programs. Finally, theinformation portal at www.bio-m.org offers an extensive com-pany database, news and eventsupdates as well as a popular jobforum.
The DigiMed Bayern consorti-um anticipated the situation
DigiMed Bayern
of 82. 13 countries have above 50points and mostly significantlymore. The study confirms theurgent need for activities such asDigiMed Bayern.
The leadership team of DigiMed Bayern at the kick-off meeting: Prof. Heribert Schunkert(German Heart Centre), Prof. Horst Domdey (BioM), Dr. Huber (StMGP), Dr. Georg Münzen-rieder (StMGP), Dr. Anand Schwenk-von Heimendahl (StMGP), Dr. Jens Wiehler (BioM) (fromleft to right).
Prof. Jan Baumbach from TU Munich started the public lecture series with the topic"Systems Medicine: A big data driven disruptive view on current medicine".
Contact:
DigiMed Bayern
c/o BioM Biotech Cluster DevelopmentGmbH
Dr. Jens [email protected]
Am Klopferspitz 19aD-82152 MartinsriedPhone: +49 89 89 96 79 0Fax: +49 89 89 96 79 79
Learning from theEuropean leaders: DigiMed
Bayern lecture series
About BioM
IGZ Würzburg is the largestbusiness incubation centre inLower Franconia. Opened in De-cember 2001, it has since providedsome 2,500 m2 lab and 3,000 m2
office space to technology-orientedentrepreneurs in their formativestages at competitive prices. Alllabs have high-tech equipment andcan be upgraded to the highersecurity standard S2. It also pro-vides conference and seminar facili-ties as well as consultancy services,which are currently being used by28 companies with some 310employees. The centre aims atsafeguarding jobs, creating net-works and synergies as well as pro-moting the region scientifically andeconomically. The facility is run bya separate operating companywhose shareholders include thecity and district of Würzburg,Sparkasse Mainfranken (savingsbank) and the Würzburg-Schwein-furt chamber of commerce (IHK).
With its research centres, researchgroups, and postgraduate schools ofmedicine and life sciences, the Julius-Maximilian University ranks amongthe most successful universities inGermany. The Rudolf-VirchowCentre for Experimental Biomedi-cine is one of the DFG-funded cen-tres of excellence focussing on theidentification of new target proteinsin cancer, cardiovascular, auto-im-mune and inflammatory diseases,
which can be the basis for improveddiagnosis and treatment. The dualcentre of internal and operativemedicine (Doppelzentrum für Innereund Operative Medizin) of the Uni-versity clinic Würzburg the Univer-sity Clinic Würzburg has excellenttechnical equipment and offers idealconditions for patient care as well asbasic and clinical research. Located inthe immediate vicinity is the Com-
prehensive Heart Failure Centre(CHFC), an integrated research andtreatment centre for cardiovasculardiseases, which moved to a modernnew building in 2016. The Compre-hensive Cancer Centre (CCC) wasestablished at Würzburg university
hospital in 2011 and is recognised asa centre of excellence for oncologyby German Cancer Aid (DeutscheKrebshilfe). The interdisciplinarybank of biomaterials and data Würz-burg (ibdw), established in 2013, isone of five nationwide databaseswhich are an important prerequisitefor a better understanding of diseasesand disease mechanisms. The Fraun-hofer project group for the investiga-tion of regenerative technologies foroncology was integrated in 2014 aftera positive evaluation in the newlyfounded „Regenerative therapies forOncology and MusculoskeletalDiseases“ translational centre, whichis funded by the Free State of Ba-varia. Within the scope of the Nord-bayern initiative, launched in 2014,Würzburg's scientific excellence isbeing further expanded in the lifesciences. This includes, amongothers, the establishment of aMax Planck research group forsystem immunology to investigatethe immunotherapy of cancer andother diseases, the establishment of aHelmholtz Institute for RNA-basedInfection Research (HIRI) as well asthe “Center for Computational andTheoretical Biology (CCTB)”.
IGZ Würzburg –where knowledge
becomes business
IGZ
Wü
rzb
urg
The enrolment of patients for theclinical phase 3 was started in August2016 based on the very good results inclinical phase 2: the test substanceRonopternin (VAS203) of vasopharmGmbH from the IGZ Würzburg affectsthe increase in cranial pressure intraumatic brain injury patients
Würzburg has huge potential to offer when it comes to the health industry, biomedicine andbiotechnology as well as medicine and medical technology. The "Innovations- und Gründerzentrum"IGZ Würzburg (innovation and business incubation centre) is a major player in developing, profilingand networking the local scientific and business community.
IGZ, the innovation and business incubation centre, is located in the science park on theWürzburg-Ost industrial estate (Gewerbegebiet).
Würzburg – a force to bereckoned with in life sciences
Northern Bavaria business plan com-petition: since 2007 prize-win-ners have come regularly fromWürzburg life sciences with theteams CALPORTIN Pharma-ceuticals, CoBaLT, SmartmAb,Mablife, Cherry Biolabs, RealT-Vac, and AIM Biologicals. Inorder to promote business ideas,it was possible to gain over 16million Euros in public funding(4x GO-Bio, VIP, m4 award,medical valley award, EXIST-Forschungstransfer and EXIST-Gründerstipendium). Four start-up companies that have emergedfrom the pre-seed start-up pro-grams have moved into the IGZ.Further start-up companies areexpected in the coming years.
At the IGZ Würzburg, a structuredprogram is pursued above all in orderto further develop the potential of lifesciences in the region. Start-up com-panies, company relocations and ex-isting companies are promoted andgiven intensive support in cooperationwith the Bavarian Ministry of Econo-mic Affairs, the Würzburg universitycolleges, BayStartUP GmbH and thecity of Würzburg economic develop-ment department. The incubationcentre promotes the networking ofregional companies and research insti-tutions in the field of biotechnologyand medical technology and supportstheir visibility through the platformBioRegion Würzburg (www.biore-gion-wuerzburg.de). Furthermore, asregional partner in Lower Franconia, itensures efficient networking with theBavarian biotechnology cluster, theMedical Valley in Erlangen and theexcellence initiative m4 in Munich.
Together with local universities,IGZ Würzburg has developed acomprehensive program for pro-moting start-up activities in theregion. Young scientists are of-fered advanced trainings courseswith an economic and branch-specific focus. Technology scoutsat colleges and research institu-
IGZ Würzburg
tions in the region are screeningresearch results for new businessconcepts with high economicpotential at early stages. Oncepromising concepts and entrepre-neurial teams are identified andmotivated, they will be supportedon the way to their own companythrough intensive coaching, con-sulting and networking. As mem-ber of the "Three Business Cen-ters in Würzburg" (www.gruen-derzentren-wuerzburg.de), theIGZ Würzburg works closelytogether with the “Technologie-und Gründerzentrum” TGZ Würz-burg (Technology and StartupCenter) and the “Zentrum fürDigitale Innovationen” ZDIMainfranken (Center for DigitalInnovations). The new initiative “Gründen@Würzburg.de” (www.gruenden.wuerzburg.de) supports the net-working of founders and startupsin Würzburg.
In recent years, in close coopera-tion with universities and Bay-StartUP, IGZ Würzburg hasdone the initial work for creationof many new jobs at the incuba-tion centre. Successful supportby the IGZ and partners isreflected in the scoring of variousWürzburg start-up projects in the
IGZ Würzburg has a comprehensive service packagefor young companies:
Hire of 3,000 m2 office space and 2,500 m2 lab space at competitive pricesFlexible rental possible - from small units to building tractsHigh-tech equipment, labs can be upgraded to the S2 security standardSupport in preparing and updating business plans, grant applications andinitiating collaborationsAdvice on business strategies, business models, patent and brand strategies,quality management and quality assurance and corporate managementquestionsAdvice on financial planning and financing, support in investor talks andfinancing rounds as well as when negotiating with strategic, licensing andcooperation partners.
Other tasks include the following:
regional and supraregional networkingnetworking academic and industrial partnerscollaboration in the creation and further development of a constructiveclimate between regional companies and institutions in Würzburg and theMainfranken region
Start-up support bears fruitSupport for entrepreneurs
Networking - locallyand in Bavarian clusters
Klaus Walther
Director
E-Mail: [email protected].: +49-931-37-23 19Fax: +49-931-37-34 23
Dr. Gerhard Frank
Project Manager
E-Mail: [email protected].: +49-931-78 08 57 11Fax.: +49-931-78 08 57 22
Contact:
Dr. Jennifer Gehring
Project Manager
E-Mail: [email protected].: +49-931-78 08 57 12Fax.: +49-931-78 08 57 22www.igz.wuerzburg.dewww.bioregion-wuerzburg.de
Multi-resistant pathogens are alreadycausing more than 6‘000 deaths peryear in Germany. While this num-ber amounts to 23‘000 in Europe, anestimated 700‘000 victims are seenon a global level with rising tenden-cy. In 2050, we will be looking at theinconceivable number of 10‘000‘000deaths worldwide as projected by theInter Agency Coordination Groupon Antimicrobial Resistance. In 2013,the US Center of Disease Controland Prevention published calcula-tions based on which the associatedeconomic cost amounts to 300
billion USD annually, taking intoaccount charges to the healthsystem and loss of productivity. Meanwhile, these or similar reportsfrom the media are seen on a nearlydaily basis. It is high time for us tomake all means available in order tosuspend the imminent catastropheand to develop novel concepts whichwill help face and oppose thesedevelopments. The Bavarian government has sincereacted and taken first steps in theright direction with the joint actionplan against antibiotic resistance andthe foundation of the recent network
program “New Strategies AgainstMulti-Resistant Pathogens by Meansof Digital Networking”. In recentyears, specific measures have beentaken to improve the conditions forresearch in Bavaria, resulting in ahigh-performance and innovative lifescience landscape for the Free Stateof Bavaria. This has created thepreconditions for a rapid reactionto international trends in the area ofmolecular biology, alongside theinitiation and promotion of key areasof research. The already implemen-ted programs such as the BavarianGenome Research Network (Bay-
Research network in Bavaria:New Strategies AgainstMulti-Resistant Pathogens by Means
of Digital Networking (bayresq.net)
bayresq.net
Fig. 1: In 2009, bacteria could not grow around the antibiotic spots. In 2019, bacterial growth will hardly be stopped by the antibiotic
spots
Where do we stand today?
Working together against multi-resistantpathogens
Antibiotic resistance
Gene), the Bavarian Network forImmunotherapy (BayImmuNet) andthe Bavarian Research Network forMolecular Biosystems (BioSysNet)are convincing examples. The current program has issued a callfor applications in May and has there-by launched a new network that willaddress the challenges associated withthe rapid development of multi-resis-tant pathogens (Fig. 1). Of course, thisglobal threat is also being perceivedon an international level and by now,many other funding programs arebeing initiated by national and inter-national organizations. Their focuslies primarily on hospital hygiene,antibiotic stewardship, the develop-ment of antibiotics of last resort andthe discovery of novel pharmaceuticalcompounds. In addition, methods forfaster diagnostic detection, for whichthe technical foundations are alreadyin place, but which have so far notreached the clinics due to high costs,are being explored by a range of pro-grams. All of these are indeed impor-tant approaches in order to avoid – atleast for some time – a further wor-sening of the situation. However,none of the known programsacknowledges the fact that funda-mental research in the area of infec-tious diseases has been neglected formany years. This is based on thewidely held notion that antibiotics areeasily available, therefore bacterialinfections are treatable and conse-quently this research area is conside-red economically unprofitable. This isa big mistake, as it now turns out. Weevidently require intensive basic rese-arch with regards to the followingquestions
host-pathogen interactionscomposition of and interactionwith the human microbiomedevelopment and spread of resistancesimmunological and other host-based approaches (as well as theirdeeper understanding for the pre-vention and control of infection)
as a basis for the later development ofinnovative strategies to face theemerging problems. This is why this
companies to be able to cover thedevelopment cost through subse-quent sales, especially since newercompounds are initially given only inextremely threatening cases. That isnot exactly an incentive for compa-nies to invest large sums of moneyinto the development of new subs-tances.
Alongside the efforts made in thearea of life sciences, concrete approa-ches to specifically implement shareddata management from the early pha-ses of knowledge generation onwardsare needed. This is the only way howto ensure an effective interdisciplinarycooperation and therefore lay thefoundations for successful collaborati-on in order to remain competitive onan international level. Therefore, de-liberate application of modern datausage and data networks on behalf ofthe project partners in the network isa new aspect of bayresq.net comparedto previous networks. The challengeconsists in creating the right conditi-ons for the network projects so thatall partners involved in the data net-work can access the jointly developed
bayresq.net
new Bavarian funding program issuch an important component of ourresearch landscape. Only by gaining abetter understanding of fundamentalprocesses and novel insight into cau-sal relations, will we be capable ofdeveloping effective solutions for thishighly relevant and complex issue inthe future.The focal point of this program is aninterdisciplinary approach that allowsexploring completely new paths.Many processes which take place bet-ween host and pathogen, such as thequestion of how the existence ofother microorganisms affects a be-ginning infection, are not yet under-stood on many levels. Researchapproaches regarding the therapy ofinfectious disease with means otherthan antibiotics have been neglectedfor many years. However, preciselythose methods providing an alter-native to antibiotic treatment are nowbecoming increasingly important.Another process is threating to emer-ge: more and more pharma compa-nies are withdrawing from researchand production of novel antibiotics.The time from development to pro-duction is considered too long for
Digitization
Fig. 2: In bayresq.net, interdisciplinary groups and modern data management are to be
combined into a new entity
data in an individual and user-friend-ly way. To this end, the bayresq.netmain office plans to offer, maintainand optimize superordinate datamanagement for all project partners.The targeted implementation of mo-dern data networks and data usageamong project partners should provi-de all scientists with the opportunityto access, analyze, manage and usenewly acquired data immediately. All of this forms the basis for creatinga sustainable and digital added value,that could potentially benefit thewider public, the field of medicine,professional users and public instituti-ons, for example in the form of webservices or apps.
bayresq.net will be funded by theBavarian State Ministry of Scienceand the Arts with more than 10 mil-lion Euro in total over a period of fiveyears. The plan is to finance up toseven interdisciplinary researchgroups from universities across Bava-ria. Each research group is composedof 2-3 collaboration partners, it is alsopossible to include central academiccore facilities from areas such assequencing, proteomics or meta-bolomics within the cooperation.Prof. Dr. Horst Domdey, managingdirector of the BioM Biotech ClusterDevelopment GmbH and BioM AGin Martinsried, has been appointedscientific director of bayresq.net,while Dr. Ulrike Kaltenhauser willlead the main office at the gene cen-ter in her capacity as managing direc-tor. An international panel of experts,the “scientific advisory board” of thenetwork, evaluates and accompaniesthe program and particularly makesrecommendations regarding the rese-arch groups‘ performances.
The high core competency of Bava-rian universities in the areas of lifescience and data management is animportant prerequisite for the propo-sed program. The same holds truefor the area of infection research, as
we have proven expertise in the sec-tor of immunotherapeutic research,microbiome and epidemiology. Thiscan be seen in the leading-edge clus-ter m4 of BioM, the research net-works mentioned above, the GermanCenter for Infection Research(DZIF), the Research Center forInfectious Disease in Würzburg, re-search groups at outstanding Bavarianuniversities as well as numerous otherprojects at many more Bavarian insti-tutions. As important research teamsare established at all of these impor-tant centers, the challenge now is toconnect and to consolidate their ex-pertise in the areas of both basic rese-arch and establish a joint data mana-gement, in order to collectively findsolutions to the upcoming challenges(Fig.2). Only by staying up to date onall levels of research, can we competewith research institutions such as theETH Zürich or elite universities inthe UK or the US and remain visibleas collaboration partners on an inter-national level.
Nowadays, the risk derived from anti-biotic resistant pathogens has reachedglobal awareness. Many of the appli-cation-oriented funding programsthat are currently available to scien-tists may contribute to momentaryrelief in this critical situation. Howe-ver, bear in mind that we must antici-pate a severe worsening of the situa-tion based on microorganisms de-veloping many new resistances in thefuture. Only based on highly mo-tivated basic research, using all avail-able technical means and at the sametime bringing together specialiststhrough joint data management,can we hope to establish new treat-ment and prevention opportuni-ties for infectious disease, whichwill contribute to facing the immi-nent threats. As long as basic re-search does not deliver new results,we won‘t be able to provide new stra-tegies of application. By funding this program, the FreeState of Bavaria intends to make a re-gional contribution to provide novel
strategies for this international chal-lenge in the future. Sooner or later,collaboration on a global level will benecessary to prevent greater harm tohumanity. Therefore, we require fastand uncomplicated informationchannels connecting all scientists.Precisely this aspect lies at the cen-ter of the new program. A large pro-portion of industrial companies hasbeen relying on digital systems formany years to ensure a smooth andsafe flow of information between allqualified partners within the valuechain. This trend is now also beco-ming increasingly important inscience. Through bayresq.net, thisprocess will be greatly acceleratedand optimized in the Free State ofBavaria. For all of the reasons men-tioned above, Bavaria is given a uni-que opportunity with bayresq.net torefocus on the neglected devel-opments of basic research in thisarea and thereby take a lead. Basicscience and the knowledge on corre-lations between detailed facts are theprerequisite for novel solutions,which are dearly needed in the futu-re. Although we should be awarethat the problem of antibiotic resi-stances cannot be solved on a per-manent basis, we can at least aspireto lay the foundation to manage it inthe long term.
bayresq.net
Dr. Ulrike
Kaltenhauser
Director of theOfficebayresq.net
Authorinformation:
Genecenter of the LMU Munich
Feodor-Lynen-Str. 2581377 MunichPhone: +49-89-218071021E-mail:[email protected]
Information onthe new program
Preconditions in Bavaria
Outlook
which are circulated are old news,but still worth mentioning.
False information in the health-care field items is as plentiful ascells in the human body, saysBeatrice Sonntag. The spectrumranges from nutrition and diet tofitness and psycho training, to
“Stop this sham” says communi-cations expert Beatrice Sonntag,when she established the internetportal Kindermedizin.info in2015. It was obvious for theMunich native, who spent manyyears in medical research at theLMU Munich and at HarvardUniversity, Boston, and who stu-died at the Bavarian Academy ofAdvertising e-Marketing at theend of the 1990s, that somethinghad to change.
„Fake news in the healthcarearena can do a lot of damage.Especially young parents becomeextremely distressed. “Nobodywants that, „says Beatrice Sonn-tag with great conviction.
Kindermedizin.info is gainingmore and more recognition andreal advocates, without financialhelp from outside. It just makessense in the name of health.Because the range of news, unin-tentionally published in goodfaith and lies deliberately distri-buted into the world – are anincreasing danger to the well-being of the body, mind and soul.In World Wide Web and socialmedia in all probability about 90percent of incorrect and mislea-ding promises and statements
acute and chronic diseases. Andthen there are the very drasticexamples of Fake News in themedical field. And those can havepotentially fatal consequences, asshown in a 1998 in the British topjournal „The Lancet“ publishedmanipulated work shows. Based onfalsified evidence, it was claimed
Truth - the basisfor best medicine.
Kin
de
rme
diz
in.i
nfo
"Tropical fruit is 1000 times more effective against cancer than chemotherapy." "Xylitol-containing che-wing gum reduces the caries risk".The Indian spice turmeric can relieve depression."Fake news in medicinehave been around for a long time. More than 30 years ago, a researcher painted parts of the fur of whitemice black and claimed that it involved the transplant of skin particles of a black mouse to a white mouse,in which the expected repulsion can be successfully avoided. This was proven to be wrong, as theskin particles were not able to reproduce and ended with the researcher being fired from his university.
A little smile for a big goal. With the girl's face as key visual kindermedizin.info is fightingagainst Fake News in children‘s medicine.
the communications work of theportal is becoming increasinglyimportant and extensive. In addi-tion, starting in fall of 2019, kin-dermedizin.info will supplementits range of services with semi-nars and Coaching on verbal andnon-verbal communication.
It begins with several text semi-nars. The target groups are prin-cipally those who work in thehealthcare industry and dailyinteract with patients. Neverthe-less, all of those interested fromother professional groups havethe opportunity to become moreeducated due to the creation andconception of well formulatedand structured texts. Courseswith new knowledge about bodylanguage complete the seminarseries. Special feature of all cour-ses is that the course contents arepresented in an easily understan-dable, clear and humorous fashion.
Frank Bienenfeld: „If we presenteducational materials in a fun andentertaining manner it remainseasily understandable and longerin the participants memory.“
„We are breaking new ground inknowledge transfer. And the suc-cess corroborates to continue thisway.“ Beatrice Sonntag adds:„We already accomplished andachieved a lot. But we will evenmore significantly increase ouractivities against Fake News inthe future. We owe this commit-ment to our society and especial-ly to the children of the world.
Kindermedizin.info
that a measles-mumps-rubella vac-cine significantly increases therisk of autism and colitis and istherefore dangerous. As a result,the vaccination rate in the UKdropped dramatically.
How many children were notvaccinated as a result of this „stu-dy“, who later became ill, died ofcomplications or still suffer frompermanent damage is unknown.
The fear of illness, the desire forhealth, the hope for recovery -which affects almost all people inmore or less pronounced form, playsan important part in the marketingstrategies of both small and largebusinesses in the medical arena.
„We will continue our educatio-nal work in the upcomingmonths,“ says Dr. Frank Bienen-feld. The creative director andtext coach has been partner ofKindermedizin.info since 2018, as
F.l.t.r. Dr. Nadine, Gerth, Beatrice Sonntag, Dr. Frank Bienenfeld
Contact:Kindermedizin.infoUG (haftungsbeschränkt)
CEO:Beatrice Sonntag, Dr. Frank Bienenfeld
Campus Martinsried IZB – West 1Am Klopferspitz 19, D-82152 MartinsriedPhone: +49 (0) 89 995 29 222E-Mail: [email protected]
Passionate Communicators
Since its founding in 2015, the health
portal Kindermedizin.info has been
reviewing, examining and connecting
information on child medicine and
provides annotated, verified contents.
Users will see the source of the infor-
mation and that the contents trust-
worthy and valuable.
Kindermedizin.info is an owner-
managed and independent com-
pany. As nutrition specialists, com-
munication professionals and biolo-
gists, the initiators Beatrice Sonn-
tag, Dr. med. Frank Bienenfeld, and
Dr. Nadine Gerth bring a good mix
of creativity and know-how for this
important work. A network of medi-
cal professionals, editors, conceptual
and web designers supports their
work.
Cancer is the leading cause fordeath in the western world andthe number of cancer-associateddeaths is steadily increasingmaking effective treatment op-tions an urgent yet unmet need.Numerous new treatment optionshave become available and perso-nalized therapies are emerging.To define the most effectivetherapy for a specific patient(group), precise predictive diag-nostic assays are essential. Here, twoaspects are becoming increasinglyrelevant. Firstly, as a result of acontinuing genetic evolution, themolecular heterogeneity of cancercells during the course of thedisease and specifically duringprogression from local to systemicdisease is limiting therapeutic effi-cacy by therapy escape of certaincancer cell clones. This opens thequestion on the best timing andselection of the best fitting, possi-bly stage-specific therapy for eachindividual patient. Secondly, theincreasing number of new thera-peutic options raises questionsabout their combination, side-effect in patients and interferencewith other treatments. Short-termand long-lasting side effects incancer survivors are currentlycompletely under-investigated.
The diagnostic relevance of
systemically disseminated
tumor cells.
Ninety percent of carcinoma pa-tients don‘t die of the primarydisease but of metastases. Metas-
tases are caused by few cancercells, the so called disseminatedtumor cells (DTCs) that have dis-seminated and lodged before sur-gical removal of the primarytumor into distant organs andwere not eliminated by the possi-bly applied therapy. These DTCscontinue their genetic evolutionat the distant site and conse-quently differ significantly on amolecular basis from cancer cellsin the primary tumor [1, 2].Despite this fact, current thera-pies are still selected according tothe molecular characteristics ofthe primary tumor and not thetarget cells of therapy, the DTCs.To track the molecular evolutionof cancer over time, the genotypeand phenotype of cancer cellshave to be assessed longitudinally,which is technically challenging asthe frequency of disseminatedcancer cells in organs/tissues thatare accessible by biopsies can bevery low. This is specifically truein the early phase of the diseasewhen patients present with no oronly few metastases.
Diagnostic assays to detect
disseminated tumor cells in
lymph nodes
In metastasized patients the mo-lecular diagnosis of a systemicdisease can be done by testing forthe presence of circulating tumorcells (CTCs) or cellfree tumorDNA (ctDNA) in blood. Such aliquid biopsy has the advantageover conventional tissue-biopsies
that the compliance of patientsespecially with regard to risk andsafety is much better and hencemuch more suitable for longi-tudinal tracking of the patient‘sdisease. However, the low num-ber and amount of CTCs andctDNA, respectively, limits thisapproach especially for the di-agnosis of early disease patientsand makes the development ofnew and innovative analyticaltools necessary. Individualized therapeutic deci-sions on surgery, irradiation,chemotherapy or other therapiesin early disease patients mainlydepend on the extent to whichthe disease is already systemicallypresent and are guided by para-meters such as the size of the pri-mary tumor, whether dissemina-tion to lymphnodes or otherorgans has occurred and thegeno-/phenotypic changes of can-cer cells over time. To determinewhether dissemination has al-ready occurred, lymph nodes areextirpated at the time of surgeryof e.g. breast- or lung cancer pa-tients. These lymph nodes arethen sectioned and evaluated bymicroscope-assisted histophathol-ogy for the presence or absenceof DTCs. This approach is verylaborious as up to 70 lymphnodes per patient have to be ana-lyzed depending on the cancertype. Moreover, sectioning oflymph nodes for histopathologyis not standardized and due tolimits in time and personnel only
Lydia HD -new concept for
lymph node analysisin cancer diagnostics
Lym
ph
no
de
an
aly
sis
some sections are investigated butnot each complete lymph node,which reduces the sensitivity ofthe approach. Although it isknown that the histopathology-sensitivity increases proportional-ly with the number of analyzedslides [3, 4], cancer cell clusterscan be missed even with veryextensive protocols and conse-quently lead to a false-negativediagnosis. Another disadvantageof the current histopathologicapproach is the necessary forma-lin-fixation of tissues hamperingdown-stream molecular/geneticanalyses. However, determiningthe presence or absence of thera-py-relevant mutations in detecteddisseminated cancer cells isessential for the selection ofmodern, personalized and tar-geted therapeutics [5] and willincreasingly become relevant inthe near future, especially fortherapy of tumors for which justrecently new therapies havebecome available (Figure 1). Toimprove the current lymph node
increase in the number of DTCsdoubled the risk emphasizingthat each cell matters [6]. Whenadditional prognostic factors suchas age and localization of the pri-mary tumor were included, thenumber of DTCs in the lymphnodes had a higher prognosticrelevance in multi-variate analys-es than diagnostic results ob-tained by routine histopathology.Moreover, based on the DTC-number determined by our newimmunocytologic approach, a sta-tistical survival model could beestablished which predicted thesurvival-prognosis more preciselythan current clinical staging guid-elines of the AJCC (AmericanJoint Committee on Cancer) [7].
Clinical relevance of lymph
node diagnostics
In addition, we could recentlyshow that dissemination intotumor-draining (sentinel-) lymphnodes occurs already very early,namely at a primary tumorthickness of less than 0.5 mm [1].At this time-point, disseminatedmelanoma cells still have relative-ly few mutations. Numerousmutations necessary required fortheir ability to grow out are justacquired at the distant site, in ourcase in lymph nodes. Melanoma cells having acquiredthese characteristic changes notonly grow in immunodeficientmice, but also increase the risk ofpatients to die of melanoma.These characteristic changesinclude mutations in the BRAFproto-oncogene and gains andlosses in the chromosomal re-gions harboring the tumor-suppressor CDKNA2 or theoncogene MET. In summary,identification of patients with dis-seminated cancer cells harboringthis colonization signature couldhelp in the future to more speci-fically direct patients into clinicalstudies with the ultimate goal toenable improved new therapeuticoptions for malignant melanoma.
Lymph node analysis
diagnostics, we applied principlesand technologies of the liquidbiopsy: extirpated lymph nodesare mechanically put into singlecell suspension and screened forthe presence or absence of dis-seminated tumor cells. Using thismethod, w conducted a study onmalignant melanoma over thecourse of eight years involvingmore than 1800 lymph node sam-ples from more than 1000 pa-tients [6]. Lymph nodes were bi-halved, one half was subjected toroutine histopathology, whereasthe other half was put into singlecell suspension and stained forthe melanoma-specific markergp100. This immunocytologicapproach was found to be moresensitive than routine histopathol-ogy (Figure 2) and revealed a linkbetween the presence of few,single DTCs and the poor prog-nosis of these patients. Alreadyas few as one to three DTCs permillion of lymph node cellsincreased the risk of patients todie of melanoma and a ten-fold
Fig. 1: The impact of the sentinel lymph node for personalized cancer therapy.
Dissemination of cancer cells from the primary tumor into other organs like lymphnodes happens already early during tumor development, when the primary tumoris still small and often not yet clinically detectable. During/shortly after surgicalremoval of the primary tumor, sentinel lymph nodes are extirpated. Extirpatedlymph nodes are examined for the presence/absence of disseminated cancer cells. Insome patients only single, isolated cancer cells are found which did not yet form acolony or metastasis. In other patients, small cancer cell colonies or even metastasiscan be found. Therapeutic targets can differ for each disease-stage (isolated cancercells, colony or metastasis) as cancer cells continue their genetic evolution also afterdissemination and consequently require stage-specific, personalized cancer thera-pies enabling elimination of cancer cells that have disseminated to other organsthan lymph nodes and thereby preventing the onset of lethal metastasis.
Improvement of the strategy
for routine pathology
In order to optimize the clinicaluse of the above described lymphnode diagnostics and to developan automatized method for lymphnode diagnostics we initiatedtogether with Fraunhofer-groupsthe interdisciplinary project LydiaHD-Diagnostics. The group forAutomation in Medicine and Bio-technology of the FraunhoferInstitute for ManufacturingEngineering and Automation IPAin Mannheim has developed theTissue-Grinder, a device whichgently separates cells withoutaffecting their viability. It also
allows the simultaneous, but inde-pendent processing of numerouslymph nodes, which is an absolutepre-requisite for its utility in rou-tine pathology. In the next step,cancer cells are identified with aspecific immunocytologic staining,detected and quantified by mi-croscopy. This last step was rely-ing so far on manual inspection ofdiagnostic specimen by specifical-ly trained personnel and was there-fore very time and personnel-intensive. Through the collabora-tion with the Fraunhofer Institutefor Integrated Circuits IIS inErlangen, we could fully automa-tize these steps significantly redu-
cing time and costs which is man-datory for a broad application inroutine pathology. To subsequentlydecide on the optimal therapeuticregimen for individual patients,detected cancer cells can be indi-vidually isolated and analyzed formolecular changes. These mo-lecular tests have already beendeveloped at the Division Person-alized Tumor Therapy at theFraunhofer Institute for Toxicol-ogy and Experimental MedicineITEM-R in Regensburg togetherwith the Chair of ExperimentalMedicine and Therapy Researchof the University of Regensburg.The method is based on the
Lymph node analysis
Fig. 2: Immunocytology – a new diagnostic tool for lymph node diagnostics of cancer.
For Immunocytology (A), lymph nodes are disaggregated, put into single cell suspension and fixed on slides, which allowsstaining, detection and precise quantification of cancer cells. Each ten-fold increase in the number of disseminated cancer cellsincreases the risk of e.g. melanoma patients to die of their cancer (Ulmer PLOsMedicine 2014). Detected cancer cells can be isolat-ed for further molecular profiling to identify relevant therapeutic target molecules by single cell genomics or panel-sequencingof selected mutations. Immunocytology-based lymph node diagnostics has a higher sensitivity than current routine histopatho-logy. Especially small cancer cell deposits or single, isolated cancer cells are detected more frequently as the immunocytologyapproach examines the complete lymph node and is independent from the number of tissue-sections or the location and distri-bution of the cancer cells (B, C).
amplification of the DNA ofsingle cells and has been alreadycommercialized as Ampli1TMWGA (Menarini Silicon Biosys-tems). All processes in the work-flow of Lydia HD-Diagnostics aresupported and accompanied bythe software Merlin, which wasspecifically developed by the IPAand includes assessment anddocumentation of the individualsteps in the work-flow from pro-cessing of samples up to a medicalreport (Figure 3).
Summary
The new automatized LyDiaHD-Diagnostic does not onlyprovide a more exact, but alsofaster and economic work-flowthan current diagnostic methodsand enables reliable and sensitivediagnostic of the disease also inpatients presenting with only fewdisseminated cancer cells. Thiswork-flow in combination withgenetic information from dissemi-nated cancer cells will enable doc-tors to select the most suitabletherapy for their patients. Thenewly developed diagnostic toolLyDia HD-Diagnostic is animportant step towards the futuredevelopment of effective personal-ized medicine.
Referenzen
1. Werner-Klein M., et al. Geneticalterations driving metastatic colonyformation are acquired outside of theprimary tumour in melanoma. NatCommun, 2018. 9(1): p. 5952. Schmidt-Kittler O., et al. From latentdisseminated cells to overt metastasis:genetic analysis of systemic breast can-cer progression. Proc Natl Acad SciU.S.A., 2003. 100(13): p. 7737-42.3. van der Ploeg, A.P., et al., EORTCMelanoma Group sentinel nodeprotocol identifies high rate of sub-micrometastases according to Rot-terdam Criteria. Eur J Cancer, 2010.46(13): p. 2414-21.4. van Diest, P.J., Histopathologicalworkup of sentinel lymph nodes:how much is enough? J Clin Pathol,1999. 52(12): p. 871-3.5. Dietel, M., et al., A 2015 update onpredictive molecular pathology and itsrole in targeted cancer therapy: a reviewfocussing on clinical relevance. CancerGene Ther, 2015. 22(9): p. 417-30.6. Ulmer A., et al., Quantitativemeasurement of melanoma spread insentinel lymph nodes and survival.PLoS Med, 2014. 11(2): e1001604.7. Ulmer A., et al., The sentinellymph node spread determinesquantitatively melanoma seeding tonon-sentinel lymph nodes and sur-vival. Eur J Cancer, 2018. 91: p. 1-10
Lymph node analysis
Dr.Bernhard Polzer1
Dr. MelanieWerner-Klein2
Dr. Christoph Klein1,2
Authors:
1 Fraunhofer Institute for Toxicologyand Experimental Medicine, Divisionof Personalized Tumour Therapy
93053 Regensburg, Germany Phone: +49 (0) 941 298480 - 23Fax: +49 (0) 941 298480 - 10mailto:[email protected]://www.item.fraunhofer.de/en/services-expertise/tumor_therapy.html
2 Experimental Medicine andTherapy Research
University of Regensburg,93053 Regensburg, Germany
Fig. 3: LyDia HD work-flow.
The flow-chart shows the individual steps in the work-flow of LyDia HD (A). The work-flow covers all necessary steps from sample arri-val at pathology up to diagnostic reporting on single cell level and incorporates four innovations that were developed within the con-sortium (B, pictures Tissue Grinder ©Fraunhofer IPA, pictures Mikroskopysystem SCube ©Fraunhofer IIS, Picture Cellisolation ©Fraunho-fer ITEM, Picture Merlin/IT ©Marc Arends/Fraunhofer IPA)
A development is sustainable if itsatisfies the needs of the presentwithout compromising the abilityof future generations to meettheir own needs.‘ This sentencewas already written in 1987 in thereport of the Brundtland Com-mission and accurately describesthe core of sustainability, whichcan only be achieved through theconsistent application of the con-cepts of efficiency, consistencyand sufficiency. Thanks to the continuouslyincreasing use of industrial bio-technology and ‚sustainable eco-nomy‘ in more and more econo-mic sectors, Bavaria is making animportant contribution to preserv-ing essential resources for futuregenerations.
With the start of the ‚ClusterOffensive‘ in 2006, proclaimed bythe Bavarian Ministry of EconomicAffairs, the rise of biotechnologyand other future-oriented indus-tries in Bavaria began. As a resultof this political initiative, severalclusters emerged with the aim ofstrengthening both high-techindustries and traditional key sec-tors of the Bavarian economy. Atpresent, 17 clusters, in just asmany different fields of compe-tence, support the five mega-trends defined for Bavaria: ener-gy, health, digitization, materialsand mobility.In 2008, the ‚BioIndustry 2021‘cluster competition initiated bythe federal government gave rise
to today’s Industrielle Biotechno-logie Bayern (IBB) NetzwerkGmbH. The network and servicecompany based in Martinsriednear Munich focuses specificallyon the promotion of industrialbiotechnology and sustainableeconomy. Initially fully co-fi-nanced by the federal govern-ment, the state and industry, sincethe end of 2013 the Free Statealone has supported the companyfrom public side. Currently, IBBNetzwerk GmbH finances itselfto a large extent with about 75 per-cent of the turnover from acquiredprojects and own funds (moreabout the company on page 12).Since 2015, the early economicpolicy decisions have been joinedby a new committee: the BavarianIn
du
stri
al
Bio
tech
no
log
y in
Ba
vari
a
Political Initiatives
Industrial Biotechnology and SustainableEconomy in Bavaria: Data, potentials, trends
The economic sectors of (industrial) biotechnology and sustainable economy are flour-ishing in Bavaria. On top of this, Bavaria has been leading the ranking of the federalstates in terms of the number of dedicated biotechnology companies for years. Direct-ly after North Rhine-Westphalia, the state with the highest population, Bavaria pro-vides the most jobs for biotech industry. In the entire secondary economic sector, the‚biologization of industry‘ is progressing and does not even stop at the mining indus-try. These positive developments are based on clever political decisions, excellent re-search by academic institutions and courageous industrial development projects. Thebalanced triad of academy, economy and politics prepares the ground for extraordi-nary biotech products and sustainable processes ‚Made in Bavaria‘...
jects, can deliver important scien-tific findings.At the Technical University ofMunich, for example, a largenumber of professors work withthis key technology across sever-al faculties and locations. Theseinclude the Chairs of Chemistryof Biogenic Raw Materials,Microbiology, Biotechnology,Biological Chemistry and Bio-process Engineering, as well asthe WACKER Chair of Macro-molecular Chemistry and theWerner Siemens Chair of Syn-thetic Biotechnology. Almost all other Bavarian univer-sities and colleges, such as Lud-wig-Maximilian-University,Munich University of AppliedSciences, Bayreuth Universityand the University of Erlangen-Nuremberg also conduct excel-lent research on industrial bio-technology.Intensive research is also carriedout at non-university researchinstitutions such as the MaxPlanck and Fraunhofer Societiesor the Helmholtz Centers.It is therefore hardly surprisingthat the sheer number of re-search topics has now reached anenormous dimension, to namejust a few:
Biopolymers from renewableraw materials or from CO2
Fuels from agricultural residuesand algaeThickening and binding agentsfrom bacterial storage materialsor proteinsnovel materials for tanks orcoatingsand much more.
In industrial biotechnology,engineering sciences, processengineering, mechanical engineer-ing and plant construction play acentral role. It is only by upscal-ing production to industry stand-ards that processes can be pro-duced cost-efficiently and pro-ducts can be competitive.
Taken together, the Bavariancompanies already reach dozensof industries. For example, theydevelop sustainable processes orproducts for the cosmetics, phar-maceutical, textile and food indu-stries, for the paints, coatings,cleaning and lubricants indu-stries, the construction andbioenergy sectors and the auto-motive and aviation industries.
As intensively as on the industri-al side, the majority of Bavarianuniversities and research institu-tions are dedicated to the trickyissues of industrial biotechnologyand sustainable economy. Withoften astounding results, theycontinuously prove that they arean abundant source of innovativeideas and, as creative partners forresearch and development pro-
Bioeconomy Council of Eco-nomic Experts, which was conve-ned as part of the ‚Initiative Bioe-conomy for Bavaria‘. It is current-ly elaborating a Bavarian bioeco-nomy strategy, which is to bepublished in 2019.
In Bavaria, many products andprocesses from the field of indu-strial biotechnology have alreadylost their infancy within just onedecade. Although this does notmean that all market barriers havealready been overcome, but theyoung industry can boast somesuccesses.Bavarian industrial companiessuch as Fritzmeier Umwelttech-nik, Thermo Fisher ScientificGeneart, UPM, Clariant Pro-dukte (Deutschland), WackerChemie, Freudenberg ChemicalSpecialities, Südzucker and Saint-Gobain Performance PlasticsBiolink are driving developmentsin the industry and conqueringmore and more economic sec-tors.They ‚biologize‘ products or pro-cess paths traditionally based onfossil raw materials and purelychemical-physical processes. Thespectrum of topics ranges fromthe fermentative production ofpolymers or aromas, syntheticbiotechnology, the production ofspecial or basic chemicals withthe aid of enzymes, or from resi-dues or wastewater, respectivley,sustainable adhesives, dyes andadditives to fuels whose produc-tion does not compete with food.However, a large number ofsmall and medium-sized compa-nies and start-ups in Bavaria alsohave ‚industrial biotechnology‘ intheir portfolio. These includeUnaveraChemLab, Electrochaea,Silantes, AMSilk, LXP Group,Naturhaus Naturfarben, DustBio-solutions, Polymaterials, Cascat,2mag, Fabes, PreSens andSusteen Technologies.
Industrial Biotechnology in Bavaria
Industrial Researchand Development
Research Landscape
Infrastructure
Processes and products of industri-al biotechnology have now foundtheir way into many everyday con-sumer goods, such as cleaningagents and textiles, food and feedor in form of bioplastics.
Especially in industrial biotech-nology, which works with livingorganisms and sometimes veryheterogeneous starting materials,the leap from laboratory to indus-trial scale is very demanding andcost intensive. Small companiesand start-ups in particular areoften unable to finance this stepon their own.Bavaria also offers solutions forthis development step so that anew approach can still reach massproduction maturity. In March2011, the TUM Technical Cent-re for White Biotechnology wasopened at the Technical Univer-sity of Munich. The Universityand the State of Bavaria investedfour million euros in the con-struction and basic equipment ofthis facility, which is unique inthe international university scen-ery. Biotechnological processesup to the cubic meter scale canbe carried out there, and highlypure products up to the kg scalecan be obtained. According to a study by Ernst &Young in 2013, Bavaria still lacksa flexible pilot or demonstrationplant that is open to all marketparticipants. This need is nowbeing considered. The construc-tion of a multi-purpose demon-stration plant in Straubing isexpected to begin in 2019/2020.With this plant, the Free State ofBavaria is creating an opportuni-ty, especially for smaller compa-nies, to scale biotechnologicalprocesses up to industrial suitabi-lity. Due to its broad technicalequipment and modular structu-re, the plant will be able to scalecountless products and processes.
As mentioned at the beginning, atotal of 17 clusters in Bavaria areworking on implementing thefive major megatrends. Theactivities of the clusters speak forthemselves: around 8,500 playerscooperate in their networks, ofwhich around 6,500 come from
Bavaria. Since their introduction,these clusters have held morethan 12,000 events with over640,000 participants and initiatedmore than 1,800 projects be-tween companies and/or researchinstitutions.In the future, it will therefore beeven more important to tap inno-vation potential at the intersec-tions of different clusters and toinitiate cross-cluster projects.This should enable the best pos-sible use to be made of synergiesfor the further development ofthe Bavarian economy.Clusters and networks that are ofgreat relevance for industrial bio-technology and sustainable eco-nomy are the ‚Chemie-Cluster‘,the ‚Umweltcluster‘, the ‚MedicalValley‘, the clusters in the fieldsof nutrition, nanotechnology andnew materials as well as the ‚Clus-ter Forst und Holz‘. The list isnot exhaustive, as there are alsointersections with other clusters,initiatives, networks and associa-tions in which still lies greatpotential.
In addition to the digitization ofbiotechnology, for example ‚In-ternet of Things‘ (IoT), the‚cross-linked laboratory‘, andmodeling of biotechnological pro-cesses, competitive biotechnolo-gical processes are needed thatcan be achieved above all throughintensive optimization. Further-more, the areas of synthetic bio-technology and ‚omics‘ technolo-gies, among others, still havelarge, untapped potential.
In the near future, tax incentives forresearch will be introduced in Ger-many. For Bavaria's and Germany'scompetitiveness in the internationalcontext, this instrument should befirmly anchored in the fundingscene, in addition to project funding,even after a possible test phase.
Industrial Biotechnology in Bavaria
Concept*Industrial biotechnology,
sustainable economy, bio-
economy - these terms are
often used synonymously,
but there are very different
concepts behind them.
At its core, industrial bio-
technology focuses on the
technical transformation
processes (biotechnologi-
cal), while bioeconomy
focuses more on the raw
materials (biological). For
industrial biotechnology,
it is therefore ‚irrelevant‘
which starting materials
are used if they are only
converted biotechnologi-
cally, just as it is inverse
for the bioeconomy which
processes are used to pro-
cess the biological starting
materials.
Sustainable economy can
be understood to mean an
intersection of industrial
biotechnology and bioeco-
nomy, i.e. when biotech-
nological processes for the
conversion of biologic raw
materials are used sustainab-
ly. The greatest potential
for a sustainable and en-
vironmentally friendly econo-
my is expected from this
intersection.
*The definitions described here merelyreflect our understanding of the termsused in this article, serve as a basis forcommon understanding and make noclaim to completeness or consensualrecognition.
There‘s always a jobto be done…
Trends
Cross-Clustering
Over and above, venture capitalfor start-ups in Germany - espe-cially in the biotechnology sector- is still very difficult to obtaincompared to other countries.Therefore, it will also be a greatchallenge in the future to pro-mote start-ups in industrial bio-technology and sustainable eco-nomy in the best possible way.
The aim is to make the countryfit for the future with state-of-the-art products and processesand to secure prosperity and jobswith them. Bavaria is on the righttrack.
1) Brundtland, G. (1987). Report of the WorldCommission on Environment and Development:Our Common Future. United Nations GeneralAssembly document A/42/427.
Industrial Biotechnology in Bavaria
Contact:
Industrielle BiotechnologieBayern Netzwerk GmbHAm Klopferspitz 19, D-82152 MartinsriedPhone: +49 89 540 45 47-0Fax: +49 89 540 45 [email protected]
Prof. Dr. Haralabos Zorbas
Some examples of Bavarian clusters, network management organizations and European associations in the field of industrialbiotechnology and sustainable economy are shown here. More intensive cooperation between the clusters, but also strongernetworking with European and international structures, should bring further advantages for Bavaria as an industrial locationin the future.
The Future
BioEntrepreneurship Summit 2019create the future of medicine
Munich, October 15 - 16, 2019
TranslaTUM + Munich Residence
Be part of the bioentrepreneurial ecosystem !
Don’t miss key trends shaping the industry and the future of medicine !
Meet exciting pre-seed and start-up showcases !
Learn from peers, experienced entrepreneurs and industry leaders !
Be inspired by key notes and captivating panel discussions !
Participate in workshops, clinics and other interactive formats !
Enjoy the m4 award ceremony !
accelerating biomedical innovation
The biennial event brings together all stakeholders of the bioentrepreneurial and
health tech ecosystem to inspire and to celebrate life science entrepreneurship.
silver sponsors
gold sponsor
platinum sponsor
www.bioentrepreneurshipsummit.org
gold sponsor
cooperation partners
