CBMED Broschüre_Final_WEB

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CBmed GmbH is a research center of excellence established in 2014 in Graz, Austria, focused on translational biomarker discovery and validation. 2

CONTENTS Page 5 Our Vision What we want to become by 2030 and how we will achieve it ORGANISATIONAL STRUCTURE 9 KEY PERFORMANCE INDICATORS 10 OUR PARTNERS 14 Industry partners, scientific partners and funding agencies all over the world AREA 1: DATA & TECHNOLOGIES 20 Advanced technologies within our Core Labs and Services and IT-driven approaches AREA 2: CANCER 24 Validated biomarkers for tailoring cancer therapy to individual patients AREA 3: CARDIO-METABOLIC HEALTH 26 An interdisciplinary approach of integrating metabolic, hormonal, inflammatory, and infectious disease aspects GET IN TOUCH WITH OUR TEAM! 34 Page 29 Our Individualised Biomarker Solutions CBmed offers customer-tailored contract research 1

CBmed is a public-private-partnership biomarker research company funded by the Austrian COMET programme for excellent technologies. With its headquarters in Graz, Austria, CBmed is currently working in cooperation with over 50 international partners in industry and academia on 4 continents worldwide. ROBERT LOBNIG THOMAS R. PIEBER CFO CSO CBmed aims to become a worldwide leading recognised partner who provides biomarker solutions for unsolved medical needs through our global partnerships and cutting-edge technologies. Our slogan “CBmed combines” defines our daily lives and encourages even more strategic international partnerships. Besides the existing CBmed facilities in Graz and Vienna, CBmed is partnering with the global diagnostic industry in Europe, the United States, Japan and Korea. We focus on highest quality throughout the entire supply chain, including biospecimens. 2

SCIENCE BOARD The Science Board includes the Area Leaders, Human Resources, Purchasing, Finance and Controlling, Business Development, Core Technologies, Total Quality Management and the two CEOs. It is responsible for business decisions, coordinating and developing the research programme. It monitors, steers and controls the progress of the research projects ­and makes decisions on operative and strategic changes. Chief Scientific Officer » Thomas Pieber Chief Financial Officer » Robert Lobnig Scientific Leader Area 1 Data & Technologies » Wolfgang Wadsak Scientific Leader Area 2 Cancer » Amin El-Heliebi Scientific Leader Area 3 Cardio-Metabolic Health » Markus Wallner CBsolutions Director of Business Development » Lucas Pflanzl-Knizacek Head of Core Technologies » Barbara Prietl Head of Total Quality Management, CBsolutions Coordination Third-Party Funding » Angela Jacan Head of Human Resources, Finance & Controlling, Purchasing » Petra Majcen Scientific Advisor Area Cancer » Armin Gerger Scientific Advisor Area Cardio-Metabolic Health » Harald Sourij 3

OUR VISION IS TO BECOME THE WORLD’S MOST RECOGNISED CENTRE FOR BIOMARKER RESEARCH IN PERSONALISED MEDICINE BY 2030. This will be achieved by integrating cutting-edge technologies with international and interdisciplinary expertise in the fields of cancer and cardio-metabolic health. Together with our scientific and industry partners, we will develop solutions and products for patient care and cure. 4

OUR MISSION Medical Mission » Diagnostic and prognostic biomarkers for earlier and more reliable assessment of disease and outcome » Predictive biomarkers for precise therapeutic decision-making and monitoring » Discovery, validation & translation of biomarkers for personalised medicine with a focus on cancer & cardio-metabolic diseases Scientific Mission » Liquid biopsies, tissue samples, imaging and clinical data from prospective and retrospective patient cohorts » Leveraging the combination of analytical technologies and systems biology (FUSION Technology) » Adoption of new, revolutionary new technologies towards next-generation biomarkers Economic Mission » Recognized provider of biomarker solutions for pharma, diagnostic, and biotech industry (CBsolutions) » Total quality management for efficient biomarker translation into marketable products » To link international R&D companies and research institutions and create new business areas for industry, spin-offs and start-ups 5

COMPANY TIMELINE Successful completion of 25 COMET research projects and 13 contract research projects with over 50 international partners on 4 continents in industry and academia. BIOMARKER New COMET funding period 2018 RESEARCH granted and successfully PROJECTS started with 11 focused 2018 research projects for 25 Mn € precision medicine. 2019 – 2022 2019 2020 Completion of 2nd COMET funding period with out­standing Start of precision oncology results for clinical translation services with global players in and new products together with Korea, Japan and big pharma. industry. 2022 6

First Consortium Board and start of 25 biomarker COMET research projects in Graz and Vienna. Recognition of CBmed 2015 Foundation of CBmed Ltd. in Graz. as first Expert Centre of BBMRI-ERIC 2014 in May 2016. BIOMARKER 2016 RESEARCH PROJECTS 2017 20 Mn € 2015 – 2018 8 60 employees working for CBmed. Foundation of the AMBRA (advanced medical biomarker research) PhD programme by CBmed in cooperation with the Medical University of Graz. VISION achieved 2030 CBmed is the world’s most recognised centre for biomarker research in personalised medicine through combining cutting-edge technologies with international and interdisciplinary expertise in the fields of canc2e0r3a0nd cardio-metabolic health. 7

SHAREHOLDERS – MAIN SCIENTIFIC PARTNERS %43.5 %20.0 %12.5 %9.5 %9.5 %5.0 The COMET programme is run by the Austrian Research Promotion Agency (FFG). Work carried out within the programme is funded by the Federal Ministry of Transport, Innovation and Technology (BMVIT), the Federal Ministry of Science, Research and Economy (BMWFW), Land Steiermark (Department 12, Business and Innovation), the Styrian Business Promotion Agency (SFG) and Land Wien (Vienna Business Agency). 8

ORGANISATIONAL CONSORTIUM BOARD STRUCTURE SCIENTIFIC AND COMPANY PARTNERS GENERAL ASSEMBLY BOARD OF SHAREHOLDERS SUPERVISORY BOARD CBmed PROGRAMME COMMITTEE SCIENCE BOARD SCIENCE BOARD & FIVE ELECTED CFO & CSO MEMBERS OF CONSORTIUM BOARD FINANCE & CONTROLLING, HR, TQM, CORE TECHNOLOGIES, INTERNATIONAL ETHICAL ADVISORY BOARD PURCHASING BUSINESS DEVELOPMENT NATIONAL AND INTERNATIONAL ETHICS EXPERT PARTNERS AREA LEADERS INTERNATIONAL STRATEGY ADVISORY BOARD INTERNATIONAL EXPERTS FROM INDUSTRY AND SCIENCE AREA 1 AREA 2 AREA 3 DATA & TECHNOLOGIES CANCER CARDIO-METABOLIC Projects Projects HEALTH Project Leaders Projects Project Leaders Project Leaders desicion-making process advice / suggestions 9

KEY PERFORMANCE INDICATORS STATUS END OF FIRST FUNDING PERIOD 7Annual Research Volume: PETRA MAJCEN TUHSAT´S Head of Human Resources, Finance 4 International & Controlling, Purchasing Biomarker Conferences in Graz and Vienna CBmed is proud of its most valuable resource 2016–2019 - our team of inspired and dedicated people. People with different backgrounds, people with 22 35 different expertise, people in different stages of their careers and people with different tasks. PhD Thesis Master Thesis We are all working together, enthusiastically sharing our common goal: to develop solutions (centre + partners) and products for patient care and cure. This drives our research. This is our passion. Our results are not only visible in scientific publica- tions. We moreover create value for translating solutions together with our partners, towards applications in future clinical practice. 10

Mn 60 EMPLOYEES FROM 10 DIFFERENT COUNTRIES Women Men 18 National and 5PATENTS International Scientific Partners 40 National and International Industry Partners 456 300 PUBLICATIONS INCL. 262 PEER-RE­VIEWED EMPLOYEES SCIENTIFIC PAPERS, ­190 PEER-­REVIEWED OF COOPERAT­ ION PARTNERS CONFERENCE CONTRIBUTIONS AND 9 CO-PUBLICATIONS BETWEEN ENGAGED IN CBmed SCIENCE AND INDUSTRY PROJECTS 2015–2018 11

PPPS FOR QUALITY BIOMARKER SOLUTIONS TAL QUALITY MANAGEMENT RETROSPECTIVE TO BIOSPECIMENS INDUSTRY BIOMARKER BIOBANKS REQUESTS BIOMARKER BIOSPECIMENS SOLUTIONS & DATA PHARMA HOSPITALS DIAGNOSTIC PROSPECTIVE BIOTECH CLINICAL COHORTS BIOMARKER BIOMARKER BIOMARKER THERAPIES & IDENTIFICATION VALIDATION TRANSLATION DIAGNOSTICS 12

MEDICAL, SCIENTIFIC AND TECHNOLOGICAL EXPERTISE Within its public-private-partnership, As a preferred partner for national and CBmed forms an approved trusted link international companies, CBmed offers offering medical, scientific and technological cooperations together with its shareholders expertise for the analysis of a wide range of and partners, the Medical Universities of Graz biological samples by accessing prospective and Vienna, where, as a trusted partner of the and retrospective cohorts in hospitals and European biobanking research infrastructure biobanks under internationally standardised BBMRI-ERIC it also has access to biobanks all conditions. over Europe. 13

OUR NETWORK OF HOSPITALS AND BIOBANKS Together with our shareholders and partners, we cover the entire value chain of moving towards patient-centered precision medicine. The Styrian Hospital Organisation KAGes together with the Medical University of Graz offer access to patient treatment and a wide range of research infrastructure. The Medical University of Graz has been ranked among the top 30 Young Universities by Times Higher Education 2018 and has a strong biomedical community, providing an excellent ecosystem for innovation in health care. BioBank Graz is a preeminent research facility located at the Medical University of Graz. It is one of the largest clinical biobanks in Europe and has been awarded the “Research BioBank of the year” (ESBB, 2014) and the “Best European Academic BioBank” (International Life Science Awards, 2016). It is currently the largest medical training institute in German-speaking countries. As the home of many highly specialised labs, the Medical University of Vienna is one of the most important research institutions performing cutting edge biomedical research across Europe. The 5 research clusters represent the focal points within the Medical University of Vienna. Amongst those, neurosciences with an exceptionally long tradition within the Vienna Medical School and medical imaging, one of the booming fields in modern precision medicine, play a pivotal role. 14

university clinics 33 CLINICAL DIVISIONS 1,563 442,230 BEDS outpatient cases per year 20 Mn SAMPLES 26 1.2 Mn 12 CENTRES FOR MEDICAL SCIENCE UNIVERSITY clinic appointments AND EDUCATION CLINICS per year 1,773 BEDS 3 clinical 553,000 outpatient cases per year institutes 15

OUR PARTNERS



INDUSTRY PARTNERS OVERALL PARTNERS WORLDWIDE (INDUSTRY & SCIENTIFIC) AUSTRIA USA REPUBLIC OF KOREA UNITED KINGDOM Europe AUSTRIA GERMANY USA AUSTRIA North America GERMANY GERMANY JAPAN AUSTRIA GERMANY AUSTRIA 16 GERMANY USA AUSTRIA JAPAN UNITED KINGDOM AUSTRIA USA AUSTRIA AUSTRIA AUSTRIA USA GERMANY Roche Diagnostics GmbH AUSTRIA AUSTRIA DEUTSCHLAND GERMANY GERMANY AUSTRIA GERMANY GERMANY AUSTRIA JAPAN AUSTRIA NETHERLANDS AUSTRIA -- -Roche Austria GmbH ■ AUSTRIA ■■■■■■■■■■ ■ GILUPi::· NANOMEDIZIN DEUTSCHLAND 20 30 40 C CCA GC T T G T G G AGC C T C T T ACAC C C �� ■ 110 120 AT C A A A G T G C T G G G C TC C G G TG C G T T sex female &dll!&- .. tumor patient c., yes 200 210 G G TG G G G AGC A C G AC mal): ■ o Colon :J Prostate Recurrence: o yes

























OUR RESEARCH APPROACH Individualised Precision Oncology HIGHER RESPONSE / RELAPSE-FREE SURVIVAL DRUG COMPUTATIONAL METHODS THERAPY RESPONSE A S METABOLOMIC THERAPY PROFILING B NEXT GENERATION THERAPY SEQUENCING C 29

AREA 3 CARDIO- METABOLIC HEALTH MARKUS WALLNER Area Leader Cardio-Metabolic Health Developing technologies to identify novel therapeutic options and to assess cardio-metabolic effects in vivo. Cardio-metabolic disease is a major infectious disease aspects. By utilising public health problem. It is the leading cause cutting-edge technologies, our aim is to of death worldwide with almost 20% of all develop reliable, quality-controlled, and deaths being cardiac-related. cost-effective biomarkers. These biomarkers Area 3 addresses acute and chronic will serve as diagnostic, prognostic and pathophysiological processes involved in predictive tools for identifying cardio- cardio-metabolic disease using an metabolic impairments, optimising interdisciplinary approach by integrating therapeutic approaches, and monitoring the metabolic, hormonal, inflammatory, and effectiveness of interventions over time. 30

PROJECTS AREA 3 2015-2018 Biomarkers for probiotic effects on microbiome-gut-brain axis Biomarkers to address diabesity Biomarkers for early sepsis detection Biomarkers in early detection and risk assessment of cardiovascular disease Molecular signatures as biomarkers of invasive fungal infections Biosensors for short-lived biomarkers Electrochemical biomarkers‚ detection Biomarkers of bone metabolism and in common metabolic disorders related organ systems AS OF 2019 Biomarkers in the regulation of fertility Biomarkers for cardiometabolic Minimally-invasive biomarkers for liver health and disease function Biomarkers in acute In-vivo biomarkers for inflammation cardio-reno-m­ etabolic disease states and fibrosis diagnosis and therapy monitoring Diagnostic and predictive biomarkers in disorders of fertility and metabolism Minimally-invasive broad spectrum biomarkers for NAFLD diagnosis and Microbiome-based biomarkers monitoring TEAM AREA 3 Our team consists of endocrinologists, cardiologists, nephrologists, technicians, molecular biologists, biomedical engineers, PhD students, study coordinators, clinical trial specialists and data scientists. 31

WE AIM TO REDUCE THE BURDEN OF Biomarkers for cardiometabolic health and disease Cardiovascular disease (CVD) is a major public Obesity and diabetes likely represent the health problem. Although the mortality rates most challenging threat to public health in the of CVD have decreased substantially over the 21st century. The main contributing factors for last decade, almost half of all deaths are still developing type 2 diabetes range from attributed to CVD. Biomarker-guided nutritional habits and sedentary lifestyle cardiovascular disease risk prediction, causing insulin resistance, but also include biomarker-based treatment selection, and factors like genetic/epigenetic predisposition. response monitoring have been proposed in The overall aim of this project is to recent years, but the addition of a set of investigate biomarkers for cardiovascular biomarkers to establish risk scores has been disease (CVD) risk prediction, response to moderately successful in improving treatment, and cardiovascular-related risk cardiovascular risk prediction. conditions. Method to Determine the State of the Humoral Immune System in Patients with Liver Disease Bacterial infections are common in liver cirrhosis. 100 low AGRA p <0.001 They are not easily detected, which can lead to the high AGRA development of serious complications and even 75 Time (months) death. There are no routine tests available to 10 20 30 40 predict susceptibility. A reliable, easy-to-assess, 50 and functional biomarker with the possibility of fully automated handling capable of identifying patients 25 at risk for developing infections has been developed. This biomarker is based on the cell-free (humoral) immune response of the body that can detect and kill pathogens. It utilises the growth tendencies of a 0 specific strain of bacteria in human serum to predict 0 the outcome of a patient. AGRA (Acellular growth retardation ability) predicts the occurence of severe infections in patients with liver cirrhosis, accurately identifies patients at risk of infections, and tracks treatment success (EP17181908.9). 32

CARDIO-METABOLIC DISEASE Biomarkers for Clinical Decision Support in Intensive Care In intensive care, cumulative fluid CFB balance may serve as a biomarker for FO 10% limit critical illness. The Medical University of Graz and B. Braun Melsungen AG No Flow LGD have collaborated on the development O No FloSw LC of an in-silico model of intensive care patients’ fluid balance. The model R E can describe the patients’ behaviour on fluid management over time, and Ebb phase 2 Flow phase 7 Day moreover provides a prediction of Adm. 1 34 5 6 their response throughout their stay in the intensive care unit. A patent Key: Admission to ICU (Adm.), Cumulative fluid balance (CFB), application was filed in 2018 preparing Resuscitation (R), Optimisation (O), Stabilisation (S), Evacuation (E), the model for translation into clinical Fluid overload (FO), Late conservative fluid therapy (LC), applicability. Late goal-directed fluid therapy (LGD) Electrochemical Biomarker Detection in Common Metabolic Disorders The aim of the project was to develop an Further technological developments are electrochemical detection system for urine planned and promising biomarkers in urine, biomarkers, e.g. C-peptide, widely used for including candidates for clinical purposes and diabetes patients and pregnant women. for electroc­ hemical detection, have been Basic properties of the detection system from identified for future applications. corrosion aspects to voltammetry results were established and optimised together with the industry partner. Proof of principle measure­ments have shown the detection capabilities using chip-based immunoassay at different protein concentrations. A prototype was successfully designed and included urinary collection and detection. 33

ANGELA JACAN Head of Total Quality Management, CBsolutions Coordination Third-Party Funding LUCAS PFLANZL-KNIZACEK CBsolutions Director of Business Development 34

OUR INDIVIDUALISED BIOMARKER SOLUTIONS Besides its COMET-funded projects, CBmed with a very high degree of complexity. offers customer-tailored contract research. Standardised workflows guarantee In cooperation with our partners we provide reproducible results. Highest quality a wide variety of services. Starting with the standards from sample acquisition until definition of specific research questions, our the delivery of lab results are of the utmost team can set up clinical trials, from study importance to us. Beyond on-demand design to execution, all the way to services we additionally provide joint completion. Linking our cutting-edge Core approaches to third-party funding within Technologies together with specialised Europe and abroad, together with services of our widespread scientific partner experienced consortium partners from network, we are capable of handling projects academia and industry. Selected projects » Flow cytometry analysis of the InterFAST cohort » Method establishment and mutation analysis in colon carcinoma » Biomarker research based on a retrospective clinical study with candidate expression confirmation in ovarian carcinoma using digital pathology » Biomarker research based on a prospective clinical study with candidate expression confirmation and analysis in clear cell renal cell carcinoma using digital pathology » Study design for RNA sequencing for head and neck cancer » FACS analysis for the impact of hypoglycaemia in patients with DIAbetes mellitus type 2 on PLATElet activation (DIAPLATE) study » Treg subtype FACS analysis in the peripheral blood of kidney transplant recipients » Application of an MS-platform in pulmonary hypertension disease 35

HOW TO ACCOMPLISH OUR VISION Together with our shareholders and partners, Patient Sample we cover the entire value chain moving towards Processing patient-centered precision medicine. (liquids and tissue) AUSTRIA Vienna Graz Patients CBmeds two largest shareholders, Individualised the Medical Universities of Graz and Precision Medicine Vienna, offer diverse and large patient cohorts with extensive Tailored Drugs infrastructure. Graz and Vienna are in close geographic proximity and only a short 2-hour car ride apart. 36

Patient-derived Cells Drug The research infrastructure Testing of CBmed, comprising cutting edge core technologies with highly qualified personnel, joins and combines the required resources. PRECISION Drug MEDICINE Response SERVICES Biomarker The Research Center Pharmaceutical Profiling Engineering (RCPE) is Austria’s Individualised leading research centre for Drug Formulation pharmaceutical development and product design. It supports partners in developing novel therapies and associated production routes. The Pharmaceutical and Regulatory Services (PRSG) is a company offering comprehensive services for all aspects of regulatory affairs by means of a One-Stop-Shop. It supports customers across a product‘s life cycle, either in an assisting or leading function for partial or complete marketing authorisation projects. 37

GET IN TOUCH WITH OUR TEAM! CBmed is constantly striving towards achieving its vision. Every day we commit ourselves to translate research results into applications for patient care and cure. Therefore, we are keen to meet you and your organisation. Please do not hesitate to contact us. mail: [email protected] phone: +43 316 385 28801 38

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Imprint CBmed GmbH Center for Biomarker Research in Medicine Stiftingtalstrasse 5 8010 Graz Austria +43 316 385 28801 www.cbmed.at [email protected] Companies Register No. FN422766s District Court for Civil Matters, Graz VAT number: ATU69052213 printed by: Wograndl Druck GmbH, 7210 Mattersburg Graphic Design, Production: kommunikationsbuero gmbh, 1060 Vienna Photo credits: p. 1 and 5: Sebastien Decoret, Kirsty Pargeter, everythingpossible – all: 123RF Ltd. p.2, 10, 18, 19, 20, 21, 24, 25, 28, 29, 32, 33, 36 – CBmed p. 22, 23: 3x Jarun Ontakrai, Joerg Michael Gehrke, Daniel Prudek, Luchschen – all: 123RF Ltd. Libertas Academica / Creative Commons p. 25: Kateryna Kon / 123RF Ltd. p. 26: Wikipedia / Creative Commons, CBmed p. 27: Wikimedia Commons, 3x Jarun Ontakrai, Luchschen / 123RF Ltd., CBmed 40

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