Anna van Buerenplein 1, 2595 DA, Den Haag, the NetherlandsTNO is an independent research organization based in the Netherlands. Targeted innovation is what we stand for. We develop knowledge not for its own sake, but for practical application in day to day life and for future innovations which can improve the quality of living. The unit Health and Work is dedicated to accelerate and de-risk drug development and improve patients’ lives. For this, we collaborate with partners from industry, academia, regulators, OEMs and other stakeholders. Projects can be initiated on the basis of fee for service (contract research), public-private partnerships, consulting services and EU projects. In the Unit Health and work we offer preclinical and early clinical research with translational models, technologies and scientific research that help drug and food developers to more effectively investigate the effectiveness and safety of their products. TNO constantly develops and improves it knowledge position, tools and research portfolio via so-called Public-private-partnerships (PPPs). In these collaborations we gain a lot of new insights in for example disease mechanisms, new targets and biomarkers, organ crosstalk, ADME, DMPK, etc. This knowledge can be directly used by the partners within the consortia, and by TNO in new and improved models and technologies in business to business applications. TNO is active in the following areas: Preclinical efficacy testing: TNO focuses on cardiovascular, metabolic and fibrotic diseases including dyslipidemia, atherosclerosis, (type 2) diabetes, obesity, chronic kidney disease, diabetic kidney disease MASLD and MASH (formerly known as NAFLD and NASH), Hart Failure with preserved Ejection Fraction (HFpEF), fibrosis and sarcopenia/frailty, brain inflammation, Women's Health, etc. For this we make use of proven translational and well validated in vivo and in vitro models, based on decades of experience in these areas. In our PPPs we aim to 1) further validate our models 2) gain molecular insight into the cross-talk between microbiome and organs like gut, liver, adipose tissue and even the brain to identify the key mediators of this cross-talk as well as to identify new biomarkers. This is all done in a Systems Biology approach. Preclinical ADME and DMPK: TNO has developed an ex vivo intestinal tissue model (InTESTine®) using human, pig, dog or rat intestinal tissue biopsies. Among other things TNO’s i-screen platform is used to culture human microbiome and studying host-microbe interactions as well as the effect of the microbiome on drug metabolism. The ex-vivo liver and/or kidney normothermic organ perfusion systems are used to study hepatic and renal clearance respectively, biliary excretion (liver), drug-drug interactions etc. Other technologies are on organ-on-chip, drug-transporter analyses, plasma protein binding, etc. PPPs are for instance on the development of an aerobe/anaerobe interface allowing the study of host-microbe interaction in a much more translational way. Target profiling and target intelligence platform TargetTri: By combining cheminformatics, network biology, text mining and expert opinion, TNO creates comprehensive reports on the expected safety (and efficacy) profile of a target. Such data can then be used in informed decision making around targets, ranking targets, de-risking strategies and/or designing investigative studies. In addition, TNO has developed a target intelligence platform based on text- and datamining. This platform integrates and ranks biological data on any drug target on the fly. In our MD3 (Mechanism Driven Drug Discovery) program we combine our platforms, AI, disease knowledge and (human/mice) omics data to get a molecular insight into diseases, and utilize this in identifying new drug targets or pathways that can be targeted by pharmaceutical or nutritional interventions. PPPs are setup to further develop TargetTri and our MD3 program. Other areas: - Biomarker research (systems biology approach) - Using AMS technology: testing safety of antibody-drug conjugates, studying dynamic fluxes, etc - Microbiology (including phage therapy/application) - Organ on a chip - Synthetic biochemistry

Sylviusweg 71 Leiden, the Netherlands, 2333 BE NetherlandsTNO is an independent research organization based in the Netherlands. Targeted innovation is what we stand for. We develop knowledge not for its own sake, but for practical application in day to day life and for future innovations which can improve the quality of living. The unit Health and Work is dedicated to accelerate and de-risk drug development and improve patients’ lives. For this, we collaborate with partners from industry, academia, regulators, OEMs and other stakeholders. Projects can be initiated on the basis of fee for service (contract research), public-private partnerships, consulting services and EU projects. In the Unit Health and work we offer preclinical and early clinical research with translational models, technologies and scientific research that help drug and food developers to more effectively investigate the effectiveness and safety of their products. TNO constantly develops and improves it knowledge position, tools and research portfolio via so-called Public-private-partnerships (PPPs). In these collaborations we gain a lot of new insights in for example disease mechanisms, new targets and biomarkers, organ crosstalk, ADME, DMPK, etc. This knowledge can be directly used by the partners within the consortia, and by TNO in new and improved models and technologies in business to business applications. TNO is active in the following areas: Preclinical efficacy testing: TNO focuses on cardiovascular, metabolic and fibrotic diseases including dyslipidemia, atherosclerosis, (type 2) diabetes, obesity, chronic kidney disease, diabetic kidney disease MASLD and MASH (formerly known as NAFLD and NASH), Hart Failure with preserved Ejection Fraction (HFpEF), fibrosis and sarcopenia/frailty, brain inflammation, Women's Health, etc. For this we make use of proven translational and well validated in vivo and in vitro models, based on decades of experience in these areas. In our PPPs we aim to 1) further validate our models 2) gain molecular insight into the cross-talk between microbiome and organs like gut, liver, adipose tissue and even the brain to identify the key mediators of this cross-talk as well as to identify new biomarkers. This is all done in a Systems Biology approach. Preclinical ADME and DMPK: TNO has developed an ex vivo intestinal tissue model (InTESTine®) using human, pig, dog or rat intestinal tissue biopsies. Among other things TNO’s i-screen platform is used to culture human microbiome and studying host-microbe interactions as well as the effect of the microbiome on drug metabolism. The ex-vivo liver and/or kidney normothermic organ perfusion systems are used to study hepatic and renal clearance respectively, biliary excretion (liver), drug-drug interactions etc. Other technologies are on organ-on-chip, drug-transporter analyses, plasma protein binding, etc. PPPs are for instance on the development of an aerobe/anaerobe interface allowing the study of host-microbe interaction in a much more translational way. Target profiling and target intelligence platform TargetTri: By combining cheminformatics, network biology, text mining and expert opinion, TNO creates comprehensive reports on the expected safety (and efficacy) profile of a target. Such data can then be used in informed decision making around targets, ranking targets, de-risking strategies and/or designing investigative studies. In addition, TNO has developed a target intelligence platform based on text- and datamining. This platform integrates and ranks biological data on any drug target on the fly. In our MD3 (Mechanism Driven Drug Discovery) program we combine our platforms, AI, disease knowledge and (human/mice) omics data to get a molecular insight into diseases, and utilize this in identifying new drug targets or pathways that can be targeted by pharmaceutical or nutritional interventions. PPPs are setup to further develop TargetTri and our MD3 program. Other areas: - Biomarker research (systems biology approach) - Using AMS technology: testing safety of antibody-drug conjugates, studying dynamic fluxes, etc - Microbiology (including phage therapy/application) - Organ on a chip - Synthetic biochemistry

Utrechtseweg 48 Zeist, NL-3704 HE NetherlandsTNO is an independent research organization based in the Netherlands. Targeted innovation is what we stand for. We develop knowledge not for its own sake, but for practical application in day to day life and for future innovations which can improve the quality of living. The unit Health and Work is dedicated to accelerate and de-risk drug development and improve patients’ lives. For this, we collaborate with partners from industry, academia, regulators, OEMs and other stakeholders. Projects can be initiated on the basis of fee for service (contract research), public-private partnerships, consulting services and EU projects. In the Unit Health and work we offer preclinical and early clinical research with translational models, technologies and scientific research that help drug and food developers to more effectively investigate the effectiveness and safety of their products. TNO constantly develops and improves it knowledge position, tools and research portfolio via so-called Public-private-partnerships (PPPs). In these collaborations we gain a lot of new insights in for example disease mechanisms, new targets and biomarkers, organ crosstalk, ADME, DMPK, etc. This knowledge can be directly used by the partners within the consortia, and by TNO in new and improved models and technologies in business to business applications. TNO is active in the following areas: Preclinical efficacy testing: TNO focuses on cardiovascular, metabolic and fibrotic diseases including dyslipidemia, atherosclerosis, (type 2) diabetes, obesity, chronic kidney disease, diabetic kidney disease MASLD and MASH (formerly known as NAFLD and NASH), Hart Failure with preserved Ejection Fraction (HFpEF), fibrosis and sarcopenia/frailty, brain inflammation, Women's Health, etc. For this we make use of proven translational and well validated in vivo and in vitro models, based on decades of experience in these areas. In our PPPs we aim to 1) further validate our models 2) gain molecular insight into the cross-talk between microbiome and organs like gut, liver, adipose tissue and even the brain to identify the key mediators of this cross-talk as well as to identify new biomarkers. This is all done in a Systems Biology approach. Preclinical ADME and DMPK: TNO has developed an ex vivo intestinal tissue model (InTESTine®) using human, pig, dog or rat intestinal tissue biopsies. Among other things TNO’s i-screen platform is used to culture human microbiome and studying host-microbe interactions as well as the effect of the microbiome on drug metabolism. The ex-vivo liver and/or kidney normothermic organ perfusion systems are used to study hepatic and renal clearance respectively, biliary excretion (liver), drug-drug interactions etc. Other technologies are on organ-on-chip, drug-transporter analyses, plasma protein binding, etc. PPPs are for instance on the development of an aerobe/anaerobe interface allowing the study of host-microbe interaction in a much more translational way. Target profiling and target intelligence platform TargetTri: By combining cheminformatics, network biology, text mining and expert opinion, TNO creates comprehensive reports on the expected safety (and efficacy) profile of a target. Such data can then be used in informed decision making around targets, ranking targets, de-risking strategies and/or designing investigative studies. In addition, TNO has developed a target intelligence platform based on text- and datamining. This platform integrates and ranks biological data on any drug target on the fly. In our MD3 (Mechanism Driven Drug Discovery) program we combine our platforms, AI, disease knowledge and (human/mice) omics data to get a molecular insight into diseases, and utilize this in identifying new drug targets or pathways that can be targeted by pharmaceutical or nutritional interventions. PPPs are setup to further develop TargetTri and our MD3 program. Other areas: - Biomarker research (systems biology approach) - Using AMS technology: testing safety of antibody-drug conjugates, studying dynamic fluxes, etc - Microbiology (including phage therapy/application) - Organ on a chip - Synthetic biochemistry

Utrechtseweg 48, 3704 HE, Zeist, The NetherlandsTNO is an independent research organization based in the Netherlands. Targeted innovation is what we stand for. We develop knowledge not for its own sake, but for practical application in day to day life and for future innovations which can improve the quality of living. The unit Health and Work is dedicated to accelerate and de-risk drug development and improve patients’ lives. For this, we collaborate with partners from industry, academia, regulators, OEMs and other stakeholders. Projects can be initiated on the basis of fee for service (contract research), public-private partnerships, consulting services and EU projects. In the Unit Health and work we offer preclinical and early clinical research with translational models, technologies and scientific research that help drug and food developers to more effectively investigate the effectiveness and safety of their products. TNO constantly develops and improves it knowledge position, tools and research portfolio via so-called Public-private-partnerships (PPPs). In these collaborations we gain a lot of new insights in for example disease mechanisms, new targets and biomarkers, organ crosstalk, ADME, DMPK, etc. This knowledge can be directly used by the partners within the consortia, and by TNO in new and improved models and technologies in business to business applications. TNO is active in the following areas: Preclinical efficacy testing: TNO focuses on cardiovascular, metabolic and fibrotic diseases including dyslipidemia, atherosclerosis, (type 2) diabetes, obesity, chronic kidney disease, diabetic kidney disease MASLD and MASH (formerly known as NAFLD and NASH), Hart Failure with preserved Ejection Fraction (HFpEF), fibrosis and sarcopenia/frailty, brain inflammation, Women's Health, etc. For this we make use of proven translational and well validated in vivo and in vitro models, based on decades of experience in these areas. In our PPPs we aim to 1) further validate our models 2) gain molecular insight into the cross-talk between microbiome and organs like gut, liver, adipose tissue and even the brain to identify the key mediators of this cross-talk as well as to identify new biomarkers. This is all done in a Systems Biology approach. Preclinical ADME and DMPK: TNO has developed an ex vivo intestinal tissue model (InTESTine®) using human, pig, dog or rat intestinal tissue biopsies. Among other things TNO’s i-screen platform is used to culture human microbiome and studying host-microbe interactions as well as the effect of the microbiome on drug metabolism. The ex-vivo liver and/or kidney normothermic organ perfusion systems are used to study hepatic and renal clearance respectively, biliary excretion (liver), drug-drug interactions etc. Other technologies are on organ-on-chip, drug-transporter analyses, plasma protein binding, etc. PPPs are for instance on the development of an aerobe/anaerobe interface allowing the study of host-microbe interaction in a much more translational way. Target profiling and target intelligence platform TargetTri: By combining cheminformatics, network biology, text mining and expert opinion, TNO creates comprehensive reports on the expected safety (and efficacy) profile of a target. Such data can then be used in informed decision making around targets, ranking targets, de-risking strategies and/or designing investigative studies. In addition, TNO has developed a target intelligence platform based on text- and datamining. This platform integrates and ranks biological data on any drug target on the fly. In our MD3 (Mechanism Driven Drug Discovery) program we combine our platforms, AI, disease knowledge and (human/mice) omics data to get a molecular insight into diseases, and utilize this in identifying new drug targets or pathways that can be targeted by pharmaceutical or nutritional interventions. PPPs are setup to further develop TargetTri and our MD3 program. Other areas: - Biomarker research (systems biology approach) - Using AMS technology: testing safety of antibody-drug conjugates, studying dynamic fluxes, etc - Microbiology (including phage therapy/application) - Organ on a chip - Synthetic biochemistry

Zernikedreef 9, 2333 CK, Leiden, The NetherlandsTNO is an independent research organization based in the Netherlands. Targeted innovation is what we stand for. We develop knowledge not for its own sake, but for practical application in day to day life and for future innovations which can improve the quality of living. The unit Health and Work is dedicated to accelerate and de-risk drug development and improve patients’ lives. For this, we collaborate with partners from industry, academia, regulators, OEMs and other stakeholders. Projects can be initiated on the basis of fee for service (contract research), public-private partnerships, consulting services and EU projects. In the Unit Health and work we offer preclinical and early clinical research with translational models, technologies and scientific research that help drug and food developers to more effectively investigate the effectiveness and safety of their products. TNO constantly develops and improves it knowledge position, tools and research portfolio via so-called Public-private-partnerships (PPPs). In these collaborations we gain a lot of new insights in for example disease mechanisms, new targets and biomarkers, organ crosstalk, ADME, DMPK, etc. This knowledge can be directly used by the partners within the consortia, and by TNO in new and improved models and technologies in business to business applications. TNO is active in the following areas: Preclinical efficacy testing: TNO focuses on cardiovascular, metabolic and fibrotic diseases including dyslipidemia, atherosclerosis, (type 2) diabetes, obesity, chronic kidney disease, diabetic kidney disease MASLD and MASH (formerly known as NAFLD and NASH), Hart Failure with preserved Ejection Fraction (HFpEF), fibrosis and sarcopenia/frailty, brain inflammation, Women's Health, etc. For this we make use of proven translational and well validated in vivo and in vitro models, based on decades of experience in these areas. In our PPPs we aim to 1) further validate our models 2) gain molecular insight into the cross-talk between microbiome and organs like gut, liver, adipose tissue and even the brain to identify the key mediators of this cross-talk as well as to identify new biomarkers. This is all done in a Systems Biology approach. Preclinical ADME and DMPK: TNO has developed an ex vivo intestinal tissue model (InTESTine®) using human, pig, dog or rat intestinal tissue biopsies. Among other things TNO’s i-screen platform is used to culture human microbiome and studying host-microbe interactions as well as the effect of the microbiome on drug metabolism. The ex-vivo liver and/or kidney normothermic organ perfusion systems are used to study hepatic and renal clearance respectively, biliary excretion (liver), drug-drug interactions etc. Other technologies are on organ-on-chip, drug-transporter analyses, plasma protein binding, etc. PPPs are for instance on the development of an aerobe/anaerobe interface allowing the study of host-microbe interaction in a much more translational way. Target profiling and target intelligence platform TargetTri: By combining cheminformatics, network biology, text mining and expert opinion, TNO creates comprehensive reports on the expected safety (and efficacy) profile of a target. Such data can then be used in informed decision making around targets, ranking targets, de-risking strategies and/or designing investigative studies. In addition, TNO has developed a target intelligence platform based on text- and datamining. This platform integrates and ranks biological data on any drug target on the fly. In our MD3 (Mechanism Driven Drug Discovery) program we combine our platforms, AI, disease knowledge and (human/mice) omics data to get a molecular insight into diseases, and utilize this in identifying new drug targets or pathways that can be targeted by pharmaceutical or nutritional interventions. PPPs are setup to further develop TargetTri and our MD3 program. Other areas: - Biomarker research (systems biology approach) - Using AMS technology: testing safety of antibody-drug conjugates, studying dynamic fluxes, etc - Microbiology (including phage therapy/application) - Organ on a chip - Synthetic biochemistry