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3RD GLOBAL NASHCONGRESS 2020

METABOLIC SYNDROME DIABETES & NAFLD SYMPOSIUM

10-11 February 2020LONDON UK

www.global-engage .com

#NASHCongress

WARM WELCOME

3RD GLOBAL NASH CONGRESS 2020

Global Engage is pleased to announce the 3rd Global NASH Congress 2020, and co-located Metabolic Syndrome, Diabetes and NAFLD Symposium which will be taking place 10-11 February 2020 at the London Heathrow Marriott.

This established meeting featuring over 60 individual talks, panels and roundtable discussions has been purposely designed to facilitate collaboration and attract attendance from the multiple communities working on NASH, NAFLD, obesity, diabetes and metabolic syndrome. It has the USP of attracting multiple stakeholders including KOL, investigators, academia, pharma, providers and regulators, whose aim is to tackle the often overlooked NASH epidemic as well as overlapping areas and develop ground breaking and impactful treatments for patients. The meeting will focus on several key themes:

• Regulatory Updates, Commercialization and Payor Perspective• Optimising Preclinical & Translational Strategy / Models• Non Invasive Biomarkers and Diagnostic Tools• New targets for the treatment of NASH/ Fibrosis / NAFLD• Recent updates in NASH Pathogenesis• Emerging research and treatment areas - Novel targets and pathways, GLP-1 etc• Clinical Development & Trial results / design / optimization• Prevention and control / Nutrition and lifestyle• Ties between obesity, diabetes and NAFLD• Role of liver and NAFLD in insulin resistance and metabolic syndrome• Organ communication between diseases We look forward to welcoming you to the event.

CONFERENCE SYNOPSIS

Novel Biomarkers and Diagnostic Tools• Advancing biomarkers for improved

diagnosis, staging, changes and prognosis• Review of current and potential

biomarkers for each stage• Evaluation of diagnostic tools

• Improving diagnostic accuracy for identification and clinical outcome

• Patient identification• Selection of treatment• Where are new biomarkers coming

from?• Liver biopsies

• Technology Focus - Imaging and other non invasive technologies – overview, developments and methods

• Quantitative analysis of samples• Improved disease measurement,

tracking and monitoring

Preclinical & Translational Strategy and New targets for treatment of NASH/ Fibrosis• Pre-clinical development of NASH targets

• Target discovery and validation - New targets for treatment of NASH/ Fibrosis

• Preclinical & translational models – Predictive value

• Model consistency

• Marrying model identification with disease stage

• Integration of clinical data to validate existing and identify novel mechanisms and targets

• Successful compounds in the clinic – How

did they perform in preclinical models

Recent updates in NASH PathogenesisExploring factors for advances in treatment - such as:

• Genetic susceptibility

• Metabolic syndrome

• Mitochondrial dysfunction and apoptosis

• Insulin resistance

• Gut microbiome

• Combination therapies

• Gut immune system

• Prevention and treatment – Tackling the root cause by improving awareness

• Utilizing nutrition and lifestyle factors

Regulatory Updates, Commercialization and Payor Perspective• EMA / FDA – Current regulatory guidance,

interaction and expectations for the future• Regulatory pathways for approval of

products• Harmonizing clinical development and the

regulatory landscape• Nash submission experiences in the EU

and US• Payor perspective – Cost of treatment;

Reimbursement; How will this work?;Demonstration of patient benefit

• Overcoming commercialisation challenges

Clinical Development & Clinical Trial Data• Current NASH Drug Development case

studies

• Improving patient recruitment and retention for clinical trials

• Novel clinical trial design – Uniformity and harmonization of trials

• Determining clinical endpoints

• Population screening

• Identifying correct treatment for stage

• What we learned from phase 3 clinical trials in 2019

Metabolic Syndrome, Diabetes and NAFLD Symposium• Links between obesity, diabetes and

NAFLD

• Role of liver, & NAFLD in insulin resistance and metabolic syndrome

• Organ communication between diseases

• Non-invasive biomarkers, technology and diagnostic tools

• Emerging research and treatment areas - Novel targets and pathways, GLP-1 etc

• Mechanistics underlying the association between NAFLD, other diseases and CVD

• Effect of anti-diabetic drugs

• Diabetes management with end stage liver disease

• Prevention and control / Nutrition and lifestyle

• Clinical & Regulatory updates & pathways in NAFLD

• Clinical development & trial results / Design / Optimization

Cross event roundtable discussions – Including:Day 11. Clinical Trial Design

2. Liver biopsy; the gold standard

3. Collaborative projects: academia, healthcare providers, industry

4. Determining clinical endpoints

5. Insulin resistance and hyperinsulinemia

6. Use of non-invasive tests for liver fibrosis in the management of NASH/NAFLD

Day 21. Regulation of Inflammation and fibrosis

2. Influence of diet and lifestyle on NAFLD/NASH

3. NAFLD & liver transplants

4. Prevention and control – influence of nutrition and lifestyle

5. Best practices for detecting, assessing and managing suspected drug-induced liver injury signals during NASH clinical trials


SPONSORS & EXHIBITORS


SPONSORSHIP AND EXHIBITION OPPORTUNITIES AVAILABLEFor sponsorship opportunities contact Faizel Ismail/Tony Couch at:

[email protected] or call +44 (0) 1865 849841

Supporters

Content Sponsor

Gold Sponsors

Bronze Sponsor

Refreshment Break Sponsor

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CONFIRMED SPEAKERS

EDUARDO MARTINSVice President, Clinical Development – Liver Disease, Allergan

LAURENT CASTERAProfessor of Hepatology, University of Paris-VII, Department of Hepatology, Hôpital Beaujon, Clichy

WILLIAM ROSENBERGPeter Scheuer Chair in Liver Diseases, Deputy Director, UCL Institute for Liver and Digestive Health

ANDREW BILLINDirector Biomarker Sciences, Gilead Sciences

HENNING GRØNBÆKProfessor, Department Hepatology & Gastroenterology, Aarhus University Hospital

HANNES HAGSTRÖMAssociate Professor, Consultant in Hepatology, Unit of Hepatology, karolinska University hospital, Sweden

MICHAEL PAVLIDESHead of Liver Imaging, Oxford Centre for Clinical Magnetic Resonance Research (OCMR)

GURU AITHALProfessor of Hepatology and the Head of the Division for the Nottingham Digestive Diseases Centre, University of Nottingham

ANDREAS GEIERProfessor of Internal Medicine and Hepatology, Head Division of Hepatology, University Hospital Würzburg, Germany

RUI CASTROAssistant Professor, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Portugal

BEVIN GANGADHARANResearch Associate, Oxford University

NIKOLAI NAOUMOVExecutive Director, Hepatology Science and Innovation, Novartis, Switzerland

SVEN FRANCQUEChairman, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Belgium

ALEXANDER WREEProfessor, Department of Hepatology and Gastroenterology, Charité Berlin, Germany

LIAT HAYARDENYChief Scientific Officer, Galmed Pharmaceutical Ltd

ELIAS PAPATHEODOROUCEO, Genkyotex, Switzerland

MICHAEL FUCHSProfessor of Medicine, Virginia Commonwealth University and Chief of Hepatology & Liver Transplantation, McGuire VA Medical Center, USA

REBECCA TAUBChief Medical Officer and President, Research & Development, Madrigal Pharmaceuticals, USA

BINDI K. SHAHChief Medical Officer, WCG– ACI Clinical

VINOOD PATELReader, University of Westminster, UK

DEVANAND SARKARProfessor, Virginia Commonwealth University, USA

MARK A. AINSWORTHChief Medical Officer, Danish Medicines Agency, Denmark

ELI GAJRAJPrincipal Technical Adviser, NICE Scientific Advice

JOANNA DOWMANConsultant Hepatologist, Queen Alexandra Hospital, UK

TONI VIDAL-PUIGProfessor of Molecular Nutrition and Metabolism, University of Cambridge; Associate Director MRC Metabolic Disease Unit; Honorary

Consultant in Metabolic Medicine Addenbrooke’s Hospital; Scientific Director Cambridge Phenomics Centre;Associate Faculty Sanger Institute

STEFANO BELLENTANIIndependent Consultant Gastroenterologist and Hepatologist, Locarno, Ticino, Switzerland

WOLF PETER HOFMANNProfessor, Gastroenterologie am Bayerischen Platz (GBP) Germany

KARIN CONDE-KNAPECVP Global Diabetes, Cardio-renal and Translational Research, Novo Nordisk, Denmark

STEFANO GINANNI CORRADINIAssociate Professor,Division of Gastroenterology, Department of Translational and Precision Medicine, University "Sapienza" of Rome Italy

SEBASTIEN BOLZEExecutive Vice President, Non Clinical Development, Co-Founder, Poxel

HAROLD H. SHLEVINPresident and Chief Executive Officer, Galectin Therapeutics Inc. USA (NASDAQ:GALT)

HUBERT CHENChief Medical Officer, Metacrine

PATRICK VRILLANDTSenior Clinical Assessor, Dutch Medicines Evaluation Board (CBG-MEB), The Netherlands

KANITA SALICScientist, Study Director Preclinical, Metabolic Health Research, TNO, The Netherlands

DANIEL SIKKEMAVice President, Quanterix

STEPHEN WILLIAMSChief Medical officer, SomaLogic

JONATHAN RIEKVP, Musculoskeletal & Metabolic Imaging, BioTel Research

SCOTT HARRISChief Medical Officer, Altimmune

SAMI BLOMApplication Manager, Aiforia Technologies

CHRIS BYRNEProfessor Endocrinology & Metabolism, Human Development and Health Academic Unit, Faculty of Medicine, The \Institute of Developmental Sciences (IDS), University of Southampton, UK


CONFIRMED SPEAKERS

PASCALE GLUAIS-DAGORNDirector, Pharmacology, Poxel

GAUTAM MEHTA (Chair)Principal Investigator, Foundation for Liver Research

NEIL YOUNGSON (Chair)Principal Investigator, Institute of Hepatology, UK

MANIL CHOUHAN (Chair)Clinical and Academic Radiologist, UCL Centre for Medical Imaging

SANJEEV KHINDRI (Chair)Acting Chief Medical Officer, Galecto Biotech AB

BREANN E ABERNATHYPhD Candidate, University of Minnesota, USA

PAUL AFOLABINutrition Biomedical Scientist Specialist, University of Southampton, UK


JERRY COLCACSO Cirius Therapeutics (Kalamazoo MI and San Diego CA, USA)

AMALIA GASTALDELLIResearch Director of Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa Italy &Professor of Medicine, UT Health Science Center San Antonio, TX, USA

CAREL LE ROUXProfessor of Experimental Pathology, Conway Institute, Diabetes Complications Research Centre, University College Dublin, Ireland

RICHARD TORSTENSONDirector International Clinical Development NASH, Allergan


ANDREW FOWELLConsultant Hepatologist, Queen Alexandra Hospital

RUI CASTROAssistant Professor, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Portugal

TONI VIDAL-PUIGProfessor of Molecular Nutrition and Metabolism, University of Cambridge, UK

ULF RISÉRUSAssociate Professor in clinical nutrition, Head of Clinical Research Unit, Uppsala University, Sweden

WILLIAM ALAZAWIReader & Consultant in Hepatology, Barts Liver Centre, Queen Mary University of London, UK

ROYCE VINCENTConsultant Chemical Pathologist and Honorary Senior Lecturer, Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, UK

ANJA GEERTSProfessor, Department of Gastroenterology and Hepatology, University of Ghent, Belgium


HENNING GRØNBÆKProfessor, Department Hepatology & Gastroenterology, Aarhus University Hospital

ANGELA SLITTProfessor, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, USA

ALEX MIRASSenior Clinical Lecturer in Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College, UK

MELISSA PALMERCEO Liver Consulting ; Former Head of Liver Disease Development, Takeda

JONATHAN SELTZERChief Scientific Officer, WCG – ACI Clinical

CLAUS KREMOSERChief Executive Officer, Phenex AG

ELIAS KETIARMedical Director, Accelerated Enrollment Solutions

ANGELA M. VALVERDESpanish National Research Council and CIBERDEM, Principal Investigator (Basic Researcher)

FAWAZ ALZAÏD (Chair)Research Associate, Immunity and Metabolism of Diabetes, Cordeliers Research Centre, INSERM

VENUE INFORMATION

London Heathrow Marriott HotelBath Road, Heathrow Airport Hayes,UB3 5AN, United Kingdom

Located less than half a mile away from the Heathrow Airport, this four-star deluxe hotel offers comfortable, noise-free accommodations and is near attractions such as Legoland and Windsor Castle. Modern and vibrant, discover the culinary delights and more in the London Heathrow Marriott.

KEYNOTE PRESENTATION:EDUARDO BRUNO MARTINSVice President, Clinical Development – Liver Disease, AllerganCan we cure NASH with pharmacotherapyNonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and nonalcoholic steatohepatitis (NASH), its most aggressive form, can progress to fibrosis, cirrhosis, liver failure and

HCC. Weight loss can lead to resolution of NASH and regression of fibrosis, but it is difficult to attain and particularly to maintain. There has been a dramatic increase in the number of compounds targeting different aspects of the pathogenesis of NASH. As of November 2019, in clinicaltrials.gov, there were 222 active studies in NASH – 19 Phase 1, 65 Phase 2 and 8 Phase 3 – either as monotherapy or in combination.

CONGRESS SCHEDULE DAY 1 MONDAY 10TH FEBRUARY 2020

08:00-08:50

Global Engage Welcome Address and Morning Chair’s Opening Remarks: Manil Chouhan Clinical and Academic Radiologist, UCL Centre for Medical Imaging

3RD GLOBAL NASH CONGRESS / METABOLIC SYNDROME, DIABETES & NAFLD SYMPOSIUM

Registration & Refreshments

09:00-09:35

08:50-09:00

KEYNOTE PRESENTATION:LAURENT CASTERAProfessor of Hepatology, University of Paris-VII (Department of Hepatology, Hôpital Beaujon, Clichy, FranceElastography and serum biomarkers as noninvasive tools for NAFLD• Noninvasive tools are widely used in NAFLD

• They are useful to detect NAFLD and advanced fibrosis• Their utility for monitoring treatment response remains to be demonstrated

09:35-10:1010:10-10:40

WILLIAM ROSENBERGPeter Scheuer Chair in Liver Diseases, Deputy Director, UCL Institute for Liver and Digestive HealthApplication of non-invasive tests for liver fibrosis

• Can be used to identify people with liver disease• Can limit unnecessary referrals to secondary care• Can be used to monitor response t interventions

11:40-12:05

11:40-12:05

11:40-12:05

JERRY COLCACSO Cirius Therapeutics (Kalamazoo MI and San Diego CA, USA)A new insulin sensitizing agent- an approach to treating the overlapping pathology of NASH and diabetes

• Metabolic dysfunction, including insulin resistance, is a common pathology in NASH and type 2 diabetes. There is a significant overlap between type 2 diabetes and NASH.

• An unbiased approach discovered the mitochondrial pyruvate carrier (MPC) as an unappreciated target of first generation insulin sensitizers. The MPC appears to be the connection between overnutrition and the metabolic dysfunction of NASH and diabetes. MSDC-0602K was developed as a second

NOVEL BIOMARKERS AND DIAGNOSTIC TOOLS METABOLIC SYNDROME, DIABETES AND NAFLD SYMPOSIUMREGULATORY UPDATES, COMMERCIALIZATION AND PAYOR PERSPECTIVE

STEPHEN WILLIAMSChief Medical officer, SomaLogicDiscovery and validation of protein signatures for NAFLD risk and NASH statusPlasma protein patterns have long offered the promise of a rich information source that is downstream to genetic, environmental and behavioral influences.SomaScan® modified aptamer technology, measuring ~5000 proteins per sample, was applied to plasma samples from ~20,000 participants in multiple studies. Machine learning was used to derive

and validate protein-phenotype models relating to objective measures used in NAFLD prevention: alcohol consumption (AUC 0.83 below/above 14 units/wk.), liver fat (AUC 0.83, fat/no fat), impaired glucose tolerance (AUC 0.84 normal/impaired), % body fat (r2 0.92), visceral fat (r2 0.76), cardiorespiratory fitness (r2 0.71) and resting energy expenditure (r2 0.70). Serum protein models for NASH characterization (steatosis, inflammation, ballooning and fibrosis in liver biopsies) and monitoring of therapeutic impact are currently being validated; earlier models generated AUCs from 0.84-0.92. Simultaneous delivery of all these tests using SomaScan can characterize patients in clinical trials and enhance medical practice.

MARK A. AINSWORTHChief Medical Officer, Danish Medicines Agency, Consultant Gastroenterologist, Odense University Hospital, DenmarkCurrent EMA reflection paper on NASH• Overview of the current version of EMA reflection paper on NASH• Study design and endpoints: Intermediate versus long-term• Regulatory challenges in NASH

Chair: Manil Chouhan Clinical and Academic Radiologist, UCL Centre for Medical Imaging

Chair: Lopa Mishra Director and Professor of Surgery, George Washington University, USA

Chair: Harold H. Shlevin President and Chief Executive Officer, Galectin Therapeutics Inc. USA (NASDAQ:GALT)

10:40-11:40 Morning Refreshments / One-to-One Meetings / Poster Presentations Refreshment Break Sponsor



HENNING GRØNBÆKProfessor, Department Hepatology & Gastroenterology, Aarhus University HospitalFrom single to multiomic blood biomarkers for diagnosis and staging of non-alcoholic fatty liver disease

• Non-alcoholic fatty liver disease (NAFLD), has been recognized as a clinical challenge for more than 20 years. However, there is still an unmet need for better biomarkers for diagnosis of NAFLD severity and treatment response.

• Due to the complexity of NASH pathogenesis, it is unlikely that a single biomarker will suffice to diagnose NASH with inflammation and fibrosis.

• The evidence of diagnostic blood biomarkers from single markers, clinical scores to multilomics for diagnosis of NAFLD liver disease severity will be presented.

12:30-12:55

12:30-12:55

ELI GAJRAJPrincipal Technical Adviser, NICE Scientific AdviceHTA perspective on evidence generationThe talk will briefly touch upon NICE’s purpose, methods and decision-making. The talk will

focus on the design of clinical trials and outcome measures to generate evidence that will facilitate a NICE appraisal. This will include patient-relevant outcomes, health-related quality of life measures and long-term outcomes. A HTA perspective on issues relating to the development of diagnostics and the use of surrogate outcomes in trials will be outlines

12:30-12:55

AMALIA GASTALDELLIResearch Director of Cardiometabolic Risk Unit, Institute of Clinical Physiology, CNR, Pisa Italy &Professor of Medicine, UT Health Science Center San Antonio, TX, USA

Pancreas liver cross talk in diabetes and NAFLDNAFLD is a major risk factor for type 2 diabetes (T2D) due to the impairment of many metabolic pathways, including decreased hepatic insulin sensitivity and insulin secretion. Conversely, patients with T2D have a higher prevalence of steatohepatitis, liver fibrosis and end-stage liver disease. The two major hormones secreted by the pancreas, i.e., insulin and glucagon, have a major effect on hepatic glucose and lipid metabolism. Moreover, the liver clears the majority of insulin secreted by the pancreas, thus modulating peripheral insulin concentrations. The talk will focus on the cross talk between pancreas and liver and its impact on NAFLD and related risk of T2D.

ANDREW BILLINDirector Biomarker Sciences, Gilead SciencesUtility of currently available non-invasive tests (NITs) for disease staging and prognosis in patients with NASH

• NITs are a critical tool for evaluating patients and for enrolling clinical trials. The talk will discuss:

• NITs as useful tools to identify patients with advanced fibrosis due to NASH

• Prognostic value of NITs and histology• Utility of NITs for monitoring treatment response

12:05-12:30

12:05-12:30

12:05-12:30

PATRICK VRILLANDTSenior Clinical Assessor, Dutch Medicines Evaluation Board (CBG-MEB), The NetherlandsNASH is a cardiovascular diseaseThe primary endpoint for clinical trials in NASH

is a matter of debate. Because hard clinical endpoints (like liver transplantation) occur only after many years, surrogate endpoints have been suggested instead. This talk will emphasize the importance of cardiovascular endpoints like Major Adverse Cardiovascular Events (MACE: cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke). From a regulatory perspective, it will not be acceptable to ignore MACE endpoints or consider these missing data. From a methodological point of view, MACE should probably be a component of the primary endpoint. In the trial, prevention of MACE should be optimized.

11:40-12:05

11:40-12:05

11:40-12:05

generation insulin sensitizer selective for this activity.• Clinical studies confirm that MSDC-0602K has effects

similar to the first generation insulin sensitizer pioglitazone in subjects with both NASH and type 2 diabetes but without dose-limiting side effects.

ContinueContinue

CLAUS KREMOSERChief Executive Officer, Phenex AGNASH is more than just steatosis: LXR inverse agonist PX665 inhibits liver DNL but shows potent insulin sensitizing and beta cell

preserving and antifibrotic effects in relevant rodent models.LXR (Liver X Receptor) is the master regulator of de novo lipogenesis (DNL) in the liver and of triglyceride (TG) resynthesis in the intestine. Inhibiting the LXR pathway through the potent synthetic LXR inverse agonist PX665 reduces DNL in the liver but also intestinal lipid absorption resulting in potent plasma TG and liver fat lowering. Moreover, inhibiting LXR seems to have specific effects on the production and excretion of lipotoxic lipid mediators. Reducing such lipotoxic lipid species has substantial effects on beta cell preservation in islets as well as on improving overall insulin sensitivity, specifically in oxidative skeletal muscle. Thus, the LXR inverse agonist PX665 seems to be an ideal candidate for the treatment of NASH by not only ameliorating the metabolic situation in the liver but by improving the hallmarks of metabolic syndrome and type 2 diabetes systemically.



14:20-14:50

KANITA SALICScientist, Study Director Preclinical, Metabolic Health Research, TNO, The NetherlandsPreclinical translational strategies in models of NAFLD/NASH and fibrosis

Translational strategies often focus on histology and often models are used in which disease inducers are not translational. In this talk the relevance of a broader preclinical translational strategy, including human diet-based disease inducers and molecular profiling analyses to study the overlap of molecular disease signatures between NASH patients and preclinical disease models will be presented. Several examples will be given using, among others, Ldlr-/-.Leiden mice in which NASH and fibrosis can be induced without cholesterol supplementation. The mice show features of human pathology on histological and biochemical level and recapitulate molecular transcriptomics and metabolomics signatures of NASH patients. Intriguingly, the models presented allow the study of organ cross talk along the gut-brain axis and development of cardiovascular disease in NASH.

14:20-14:50

14:20-14:50

DANIEL SIKKEMAVice President, QuanterixMetabolic changes and biomarkers preceding and associated with NASH• Proglucagon peptides, Diabetes type 2

• Obesity and inflammation• Technologies to non-invasively measure biomarkers in an

ultrasensitive manner

JONATHAN RIEKVP, Musculoskeletal & Metabolic Imaging, BioTel ResearchPractical considerations for imaging in NASHThere are many ways to look at imaging

for NASH. One of the current trends is to try to replace the biopsy with noninvasive techniques to replicate the histopathological measurements. Proton-density fat fraction (PDFF) is an MRI technique that quantifies the percent of visible hydrogen protons in the liver that come from fat. This has been demonstrated to be both accurate and precise. Magnetic Resonance Elastography (MRE) can measure the stiffness of liver tissue with good reproducibility as well. Iron-corrected T1 may also be a useful measurement, but has several limitations. The question this talk hopes to answer is how to integrate these imaging techniques into a NASH clinical trial, and what are the limitations of each.

13:20-14:20 Lunch

Chair: Mike Burden Director, Conference Production, Global Engage Chair: Scott Taylor Operations Director, Global Engage Chair: Alex Miras Senior Clinical Lecturer in Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College, UK

HANNES HAGSTRÖMAssociate Professor, Consultant in Hepatology, Unit of Hepatology, karolinska University hospital, SwedenIdentifying patients with risk of adverse outcomes – where should we look more closely?

Progression of fibrosis is slow in NAFLD, and only a minority of patients develop clinically significant liver disease. The talk will focus on how to identify those with the highest risk of fibrosis progression, development of cirrhosis and liver-related death.

12:55-13:20

12:55-13:20

12:55-13:20

CAREL LE ROUXProfessor of Experimental Pathology, Conway Institute, Diabetes Complications Research Centre, University College Dublin, IrelandHow the gut talks to the brain to impact the liver

• Obesity is a disease of the subcortical areas of the brain. • The best way to reduce the symptoms of obesity is to enhance

satiety signals from the gut to the brain. • At least 10% weight loss is required to impact complications of

obesity such as NAFLD and NASH

TONI VIDAL-PUIGProfessor of Molecular Nutrition and Metabolism, University of Cambridge; Associate Director MRC Metabolic Disease Unit; Honorary Consultant in Metabolic Medicine Addenbrooke’s Hospital;

Scientific Director Cambridge Phenomics Centre;Associate Faculty Sanger InstituteAdipose tissue expandability, lipotoxicity and fatty liverOur main hypothesis is that the link between obesity and metabolic complications such as NAFLD is the ectopic accumulation of lipids. Based on this the intellectual framework of our approaches include strategies to improve adipose tissue storage capacity, promote energy dissipation and modulation of lipid networks to prevent toxic lipid formation. More specifically we will focus on the early stages of NAFLD and the transition to NASH. Also I will provide information about current efforts to identify preclinical models to study NAFLD/NASH suitable for translation.



GURU AITHALProfessor of Hepatology and the Head of the Division for the Nottingham Digestive Diseases Centre, University of Nottingham Biomarkers in Non-Alcoholic Fatty Liver Diseases

• Use of imaging biomarkers to stratify patients with NAFLD• Novel methods in MRI• Application of metabolic imaging in NAFLD

15:15-15:40

15:15-15:40

MICHAEL FUCHSProfessor of Medicine, Virginia Commonwealth University and Chief of Hepatology & Liver Transplantation, McGuire VA Medical Center, USAScreening for NAFLD in special populations

• NAFLD screening is not recommended for the general population, but can it be justified for T2DM and/or obesity?

• What screening tools can be effectively utilized for these populations and how should they be applied?

15:40-16:25 Afternoon Refreshments / One-to-One Meetings / Poster Presentations Refreshment Break Sponsor

16:25-16:50

16:25-16:50

16:25-16:50

ALEX MIRASSenior Clinical Lecturer in Endocrinology, Department of Metabolism, Digestion and Reproduction, Imperial College, UKThe impact of medical devices on diabetes and fatty liver disease

• Presentation of the most commonly used medical devices• Effects of the devices on glucose and weight• Effects of the devices on fatty liver disease

ANDREAS GEIERProfessor of Internal Medicine and Hepatology, Head Division of Hepatology, University Hospital Würzburg, GermanyIntegrating NAFLD Screening into secondary and tertiary care

• NAFLD screening is currently not recommended in the general population, though 20-30% are affected

• NAFLD diagnostic algorithms include non-invasive scores and elastometry as primary and advanced tools

• Automated screening tools in primary care as well as platforms for secondary NAFLD diagnostics are urgently needed

HENNING GRØNBÆKProfessor, Department Hepatology & Gastroenterology, Aarhus University HospitalCrosstalk between adipose tissue insulin resistance and liver macrophages in non alcoholic fatty liver disease

MICHAEL PAVLIDESHead of Liver Imaging, Oxford Centre for Clinical Magnetic Resonance Research (OCMR)Multiparametric MRI for the evaluation of NAFLD

With the increasing prevalence of NAFLD worldwide, there is an urgent clinical need for reliable methods to diagnose and stage liver pathology. Liver biopsy, the current gold standard, is invasive and limited by sampling and observer dependent variability. Magnetic resonance protocols for liver tissue characterisation have been developed and evaluated in a variety of clinical settings. Multiparametric MRI has shown excellent diagnostic performance against liver biopsy for the staging of liver fibrosis and quantification fat and iron, and good prognostic performance for the prediction of adverse clinical outcomes. Furthermore, MR based techniques show promise as tools for monitoring the effects of therapy picking up early improvements. Lastly, MRI techniques have shown superior reproducibility compared to alternatives and have been used to study liver fat and liver iron in population level studies. Collectively, the emerging evidence suggests that liver multiparametric MR techniques can be powerful tools for the assessment of patients with NAFLD, as they allow for the quantification of multiple parameters and can be applied in a variety of contexts of use.

14:50-15:15

14:50-15:40

50 MINUTE ROUNDTABLE DISCUSSIONS:TABLE 1: Clinical Trial DesignSVEN FRANCQUEChairman, Division of Gastroenterology and Hepatology, Antwerp University Hospital, Belgium

TABLE 2: Liver biopsy; the gold standardANDREW FOWELLConsultant Hepatologist, Queen Alexandra Hospital

TABLE 3: Regulation of Inflammation and fibrosisVINOOD PATELReader, University of Westminster, UK

TABLE 4: Insulin resistance and hyperinsulinemiaAMALIA GASTALDELLIHead of Cardiometabolic Risk Lab, Italian National Research Council, ItalyJERRY COLCACSO, Cirius Therapeutics

TABLE 5: Use of non-invasive tests for liver fibrosis in the management of NASH/NAFLDWILLIAM ROSENBERGPeter Scheuer Chair in Liver Diseases, Deputy Director, UCL Institute for Liver and Digestive Health

14:50-15:15

RICHARD TORSTENSONDirector International Clinical Development NASH, AllerganClinical and regulatory pathways in NAFLD - Current and future landscape

Regulatory pathways for drug development in NASH/NAFLD have evolved over several years with authorities publishing their current considerations in draft guidelines (EU/US/China). In parallel, there is ongoing activities to refined and improve efficacy markers to further evaluate the effect of new pharmacodynamic treatments for NASH. Trends, global activities and considerations for future trial design will be discussed.


RUI CASTROAssistant Professor, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Portugal miRNAs as novel biomarkers and diagnostic tools

Recent evidences have highlighted the role of microRNAs as key molecular triggers of NAFLD, by participating in the development of adipose tissue dysfunction and insulin resistance, up to their pathological role on the different liver cell types, during disease progression. Several current basic and clinical investigations have pinpointed the capacity of miRNAs to act as accurate non-invasive diagnostic and prognostic biomarkers for NAFLD, particularly those circulating within extracellular vesicles, as an alternative to the limitations posed by liver biopsy-based findings. Finally, different molecules targeting key miRNAs participating in NAFLD pathogenesis have shown promise in preclinical development, inspiring new efforts in achieving its safe, successful translation into the clinic.

17:10-17:35

17:10-17:35

ROYCE VINCENTConsultant Chemical Pathologist and Honorary Senior Lecturer, Department of Clinical Biochemistry, King's College Hospital NHS Foundation Trust, UK

The impact of metabolic/bariatric surgery on NAFLD• The potential role of bile acids in the pathogenesis of NAFLD• The altered bile acid metabolism after metabolic/bariatric

surgery• Metabolic/bariatric surgery as a treatment option for NAFLD

POSTER COMPETITION WINNER TALKSBREANN E ABERNATHYPhD Candidate, University of Minnesota, USAPolylactose, a novel prebiotic dietary fiber, reduces hepatic lipid accumulation in rats fed a high fat diet

Polylactose is a novel dietary fiber, synthesized by reactive extrusion of lactose. To evaluate its potential as a prebiotic, we determined its fermentability, effect on the colonic microbiome, and its effects on fatty liver in a diet-induced obesity animal model. We found that polylactose is a vigorously fermentable fiber and elicits a beneficial change in the gut microbiome. We also demonstrate that consuming polylactose, in the context of a high fat diet, prevents lipid and cholesterol accumulation in the liver, likely due to changes in lipid synthesis pathways, as indicated by transcriptome analysis. As these effects of polylactose were greater than those of two established prebiotics, this suggests that polylactose is a potent prebiotic and potential therapeutic agent for early stages of fatty liver disease.

POSTER COMPETITION WINNER TALKSPASCALE GLUAIS-DAGORNDirector, Pharmacology, PoxelPXL770, a new direct AMP-activated protein Kinase (AMPK) activator, demonstrates anti-

inflammatory and anti-fibrogenic effects in DIO-NASH mice model for the treatment of non-alcoholic steatohepatitisInflammation is a key event in the establishment of NASH and a major contributing factor to liver fibrogenesis. AMPK enzyme, as an energy sensor within the cell, regulates glucose and lipid metabolism in target tissues including the liver and adipose tissue and is also described as a modulator of inflammatory responses. PXL770 is a new direct AMPK activator showing beneficial effects in DIO NASH mice model. PXL770 reduced total liver inflammatory cells, decreased resident myeloid cells as well as recruited monocyte/macrophage cells, which is correlated with a concomitant decrease in plasma level of MCP-1. These effects contribute to the reduction in liver fibrogenesis. These benefits induced by PXL770 appear promising for the treatment of NASH. A phase 2a study in likely NASH patients is ongoing.

NOVEL BIOMARKERS AND DIAGNOSTIC TOOLS METABOLIC CLINICAL DEVELOPMENT SYNDROME, DIABETES AND NAFLD SYMPOSIUM

PRECLINICAL & TRANSLATIONAL STRATEGY AND NEW TARGETS FOR TREATMENT OF NASH/ FIBROSIS

16:50-17:10

16:50-17:10

POSTER COMPETITION WINNER TALKSANGELA M. VALVERDESpanish National Research Council and CIBERDEM, Principal Investigator (Basic Researcher)Effect of the hepatic extracellular vesicles in

inflammation-associated insulin resistance in non-alcoholic fatty liver diseaseCell-to-cell communication by extracellular vesicles (EVs) is an emerging issue in non-alcoholic fatty liver disease (NAFLD). In this study we found higher EVs secretion, particularly exosomes, in hepatocytes and plasma from obese mice with NAFLD compared with the controls from lean mice. Moreover, both the uptake of NAFLD-exosomes by macrophages in culture and intravenous injection of NAFLD-exosomes in mice triggered NFκB activation and a proinflammatory response. Insulin resistance was induced in hepatocytes incubated with the secretome of macrophages treated with NAFLD exosomes and in cultured hepatocytes isolated from mice injected with NAFLD exosomes. Our results identified a novel molecular mechanism in the interactome hepatocyte-macrophagehepatocyte where NAFLD exosomes (circulating or hepatocyte-derived) induced inflammation and insulin resistance through macrophages inflammatory responses.

16:50-17:10


PAUL AFOLABINutrition Biomedical Scientist Specialist, University of Southampton, UKThe use of 13C-metabolic probes to assess disease severity in Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) has reached epidemic proportions, thus becoming one of the leading causes of chronic liver disease worldwide. Liver biopsy remains the gold standard to stage NAFLD and to monitor response to various pharmacological treatments of NAFLD. However, liver biopsy has some limitations, and is not preferred by patients due to its invasiveness. Currently, there are no acceptable sensitive or specific non-invasive surrogates of liver biopsy for monitoring pharmacological treatments of NAFLD. However, recent studies have shown that the metabolism of 13C-liver metabolic probes within the hepatic mitochondria have good correlation with both histological stages and markers of liver inflammation and fibrosis. Thus, the use of these metabolic probes could be promising non-invasive surrogates of liver biopsy in patients with NAFLD.

17:10-17:35



18:00-18:25

17:35-18:00

SVEN FRANCQUEChairman, Division of Gastroenterology and Hepatology, Antwerp University Hospital, BelgiumThe adipose tissue-liver axis in NAFLD: implications for therapyAdipose tissue dysfunction and inflammation is considered an important aetiological factor in the pathogenesis of NAFLD. Not only substrates released or insufficiently

buffered by the adipose tissue, but also adipokines, inflammatory cytokines and immune cells originating from the adipose tissue impact on the liver. Hepatokines exert reciprocal influences. The adipose tissue-liver crosstalk is not only important in understanding NAFLD pathophysiology, but also in understanding the extra-hepatic consequences associated with NAFLD. This concept is also relevant in the treatment of NAFLD, which requires a systemic approach. Several drugs that impact on adiposity or adipocyte function, such as glucagon-like peptide 1 receptor agonists or peroxisome proliferator-activated receptor gamma agonists used for the treatment of obesity and/or diabetes, could therefore also be considered for the treatment of NAFLD. Liraglutide and pioglitazone have already been tested in that context. Interestingly, several of the new drugs in the pipeline for NAFLD build further on this concept and hold promise. The presentation will summarize current data on the adipose tissue-liver axis in NAFLD and discuss its potential therapeutic relevance.

DEVANAND SARKARProfessor, Virginia Commonwealth University, USARNAi strategy for the treatment of NASH: focus on astrocyte elevated Gene-1 (AEG-1)AEG-1 is overexpressed in NASH patients. A hepatocyte-specific AEG-1 transgenic mouse develops spontaneous NASH and a hepatocyte-specific conditional AEG-1

knockout mouse shows resistance to high fat diet (HFD)-induced NASH.• AEG-1 induces NASH by inhibiting PPARα, thus fatty acid β-oxidation, by increasing translation of fatty

acid synthesizing enzymes, and by activating NF-κB, a master regulator of pro-inflammatory cytokines.• Treatment with hepatocyte-targeted nanoparticles delivering AEG-1 siRNA prevented development

of NASH in mice fed HFD.

18:25 Chair's Closing Remarks / End of Day One

18:25-19:25 Networking Drinks Reception


17:35-18:00

17:35-18:00

ANJA GEERTSProfessor, Department of Gastroenterology and Hepatology, University of Ghent, BelgiumThe pitfalls of bariatric surgery in NAFLD patientsBariatric surgery is often presented as a therapy for NAFLD. However, the risk of

alcohol addiction is a major problem in this population. Development of rapid progressive liver failure is the danger that we will be increasingly confronted with.

BEVIN GANGADHARANResearch Associate, Oxford UniversityNovel serum biomarkers for NAFLD Identified using proteomicsSeveral biomarkers identified using proteomics which successfully track disease progression including ones which can discriminate healthy individuals from NAFL,

NAFL from NASH and the stages of lobular inflammation. We have developed the first antibody-free serum protein biomarker assay and are currently looking into developing a rapid point-of-care test (POCT) which would work with a single drop of finger pricked capillary blood. We are the first to publish a novel method which uses a universal calibration mix which can be used for any protein biomarker and up to six different biomarkers in a single acquisition. We are the only group who have been successful in using this novel method which has the potential to improve biomarker detection and quantitation in the clinic.

ROUNDTABLES IN DETAIL DAY 1 MONDAY 10TH FEBRUARY 2020


DAY 1: 50 MINUTE ROUNDTABLE DISCUSSIONS:TABLE 1: Clinical Trial DesignSVEN FRANCQUEChairman, Division of Gastroenterology and Hepatology, Antwerp University Hospital, BelgiumAlthough a lot of progress has been made in defining target population as well as efficacy endpoints, several issues remain debated. Liver biopsy is still the gold standard and a prerequisite in Phase 3. The role of non-invasive tools in patient selection and treatment response is increasing, but their exact value needs further validation, especially in how to define treatment response. The relation of non-invasive as well as histological endpoints with ultimate clinical outcomes also still needs to be established. How cardiovascular disease can be integrated in clinical trials remains unclear. Life style modification and treatment of co-morbidities might impact on disease natural history and influence trial results, but their standardisation in trials is challenging. All these aspects will be discussed.TABLE 2: Liver biopsy; the gold standardANDREW FOWELLConsultant Hepatologist, Queen Alexandra Hospital• Liver biopsy; still the ‘gold standard’?• What are the best non-invasive alternatives for diagnosing NASH

and related fibrosis?• Monitoring fibrosis progression and regression in NAFLD.TABLE 3: Regulation of Inflammation and fibrosisVINOOD PATELReader, University of Westminster, UKNon-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disease worldwide and is also an emerging risk factor for liver cirrhosis leading to hepatocellular carcinoma. NAFLD is also a metabolic condition that etiologically parallels with obesity, type 2 diabetes, and the metabolic syndrome, however the precise mechanisms leading to disease progression are still evolving. There are several classical key events occurring during the overlapping transition from NAFL to NASH which include, lipotoxicity, mitochondrial dysfunction, oxidative stress and toll-like receptor signalling. More recently other factors also play a pivotal trigger in the progression of NAFLD including, hepatic innate immune response; dysregulated microbiota and the role of bile acids; genetic variants (PNPLA3); dietary factors (high fructose/omega 6 fatty acids). Many of these pathways also act as initiators for hepatic stellate cell activation leading to fibrosis, indicating the complexity of identifying a single treatment for fibrosis prevention/reversal.

TABLE 4: Insulin resistance and hyperinsulinemiaAMALIA GASTALDELLIHead of Cardiometabolic Risk Lab, Italian National Research Council, ItalyJERRY COLCACSO, Cirius TherapeuticsPatients with NAFLD/NASH (with or without type 2 diabetes) are at high risk for adverse cardiometabolic issues. One of the predisposing factors may hyperinsulinemia that results both from increased insulin secretion in response to insulin resistance and inappropriately reduced hepatic clearance of insulin. We propose to discuss the following topics:• What is the impact of increased insulin resistance and

dysfunctional insulin secretion on NAFLD?• What are the ways that insulin secretion and clearance can be

measured in the clinical setting?• What is the evidence of reduced hepatic clearance of insulin in

NAFLD/NASH subjects with and without diabetes?• what are the implications of reduced insulin clearance on hepatic

metabolism?• What are the implications of this pathophysiology to drug

development?TABLE 5: Use of non-invasive tests for liver fibrosis in the management of NASH/NAFLDWILLIAM ROSENBERGPeter Scheuer Chair in Liver Diseases, Deputy Director, UCL Institute for Liver and Digestive Health

KEYNOTE ADDRESS:LIAT HAYARDENYChief Scientific Officer, Galmed Pharmaceutical LtdAramchol, a stearoyl CoA desaturase modulator, from scientific rationale to clinical phase 3 (ARMOR)Aramchol (arachidyl amido cholanoic acid) is an orally active, liver target, fatty acid-bile acid conjugate, that reduces liver fat content in NAFLD patients. In a one-year Phase 2b study, Aramchol

reduced liver fat, promoted NASH resolution and improved liver biochemistries and fibrosis, of interest was also the reduction in HbA1c. Aramchol exerts its effects in a dose response manner where 600mg was better than 400mg and placebo in all clinical end points. Aramchol has an excellent safety and tolerability profiles. Aramchol is presently being evaluated in Phase 3 study for NASH. The mechanism by which Aramchol exerts its clinical activity is down regulation of SCD1. SCD 1, a key enzyme, catalyzes the rate limiting step in the biosynthesis of monounsaturated fatty acid, involves in triglyceride biosynthesis whose loss enhances fatty acid β-oxidation. Down regulation of SCD 1 also targets the proliferation and collagen production from hepatic stellate cells and directly affect fibrosis.

CONGRESS SCHEDULE DAY 2 TUESDAY 11TH FEBRUARY 2020

08:00-08:55

Morning Chair’s Opening Remarks: Sanjeev Khindri Acting Chief Medical Officer, Galecto Biotech AB


Registration & Refreshments

09:00-09:35

08:55-09:00

NIKOLAI NAOUMOVExecutive Director, Hepatology Science and Innovation, Novartis, SwitzerlandProgress in developing combination therapies – Novartis’ approach■ 2019 is an important milestone in NASH drug development with results and learnings from the first Phase 3 trials and several large Phase 2 trials becoming available.■ Recognizing the complex pathophysiology of NASH and patients’ heterogeneity, Novartis’ approach has been focused on developing Tropifexor - a highly potent, multi-modal, non-steroid FXR

agonist - as monotherapy, as well as a therapy-backbone of several combinations, with both internal compounds and through inter-company collaborations to optimally serve the spectrum of NASH patients.• Accumulating results from clinical studies with compounds targeting different molecular pathways along with biomarker development provide the evidence-base for tailoring combination therapies according to the

disease stage and existing co-morbidities.

09:35-10:10

10:40-11:25 Morning Refreshments / One-to-One Meetings / Poster Presentations

SVEN FRANCQUEChairman, Division of Gastroenterology and Hepatology, Antwerp University Hospital, BelgiumNAFLD as a risk factor for cardiovascular diseaseThe primary cause of death in patients with NAFLD is cardiovascular disease (CVD) and NAFLD patients seem to be at increased risk compared to a matched control population, pointing towards an independent contribution of NAFLD to the development of cardiovascular morbidity and mortality. The close intertanglement of NAFLD and the metabolic syndrome make

it difficult to compile hard clinical evidence to substantiate the latter statement, although a lot of clinical data are supportive and many pre-clinical and clinical data give insight into the potential mechanistics underlying the association between NAFLD and CVD. With the emerging treatments for NAFLD, some of which also impact on metabolic factors that also impact CVD, the issue becomes particularly relevant, as NAFLD pharmacotherapy must not only be safe, but some might have a beneficial effect on CVD outcomes, which might represent an additional benefit beyond the hepatological endpoints and play a role in their indication and positioning. The presentation will summarize the current knowledge and its potential implications for the overall clinical care of patients with NAFLD.

10:10-10:4011:25-11:55

11:25-11:55

SAMI BLOMApplication Manager, Aiforia TechnologiesAdvancing discovery in liver research with AI: case studies and live demo

Dr. Sami Blom, Application Manager at Aiforia Technologies, will present case studies on how deep learning AI is being used to analyze histopathological images in NAFLD and other liver diseases. Dr. Blom will then share a live demo of the cloud-based Aiforia software to show how AI models can be trained without any coding needed. Aiforia Velocity, the latest software release of high-speed image analysis tools and features, will also be introduced.

Chair: Sanjeev Khindri Acting Chief Medical Officer, Galecto Biotech AB Chair: Neil Youngson Principal Investigator, Institute of Hepatology, UK

BINDI K. SHAHChief Medical Officer, WCG – ACI ClinicalEndpoint Adjudication Best Practices for NASH trials

The FDA guidance for Noncirrhotic NASH With Liver Fibrosis recommends Endpoint Adjudication of cardiovascular and hepatic endpoints in NASH trials. Adjudication requires a specialized process and workflow within the clinical trial. Systematic, rigorous and transparent efforts have to be made in both event identification and event evaluation for all events and suspected events. Although Endpoint Adjudication can be a complex and sensitive process, best practices have been recommended in

11:25-11:55

Chair: Angela Slitt Professor, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, USA

ELIAS KETIARMedical Director, Accelerated Enrollment SolutionsNASH Trial Recruitment: The AES SolutionNAFLD / NASH clinical research has become

crowded, with many companies and compounds competing for few available sites and patients. Accelerated Enrollment Solutions (AES) comprises a proprietary global database of 100 million households which includes thousands of confirmed / diagnosed NAFLD patients, as well as patients at high risk for NAFLD / NASH. More than 70,000 respondents have self-reported fatty liver disease in our pre-screening for related conditions, providing a ready-made audience for

Refreshment Break Sponsor

RECENT UPDATES IN NASH PATHOGENESIS METABOLIC CLINICAL DEVELOPMENT SYNDROME, DIABETES AND NAFLD SYMPOSIUMCLINICAL DEVELOPMENT

SCOTT HARRISChief Medical Officer, AltimmuneDual GLP-1 Agonists in the Treatment Metabolic & Liver Dysfunction in NASH• Obesity and excess body fat are the principal

factors behind NASH, and treating them is key to successful outcomes, not only for the liver disease, but for the systemic complications of obesity, which have even greater impact on the health of obese patients.• GLP-1s induce only modest weight loss, and other drugs in

development for NASH have no weight-loss effects at all.• Dual GLP-1/glucagon agonists are potent weight loss-

inducing and have the potential to treat both NASH and the systemic consequences of obesity.

11:55-12:20

11:55-12:20

STEFANO BELLENTANIIndependent Consultant Gastroenterologist and Hepatologist, Locarno, Ticino, SwitzerlandGlobal epidemiology of NAFLD/NASH: the new emergency epidemic?

• Update on the global epidemiology of NAFLD/NASH; • The natural history of NAFLD/NASH: towards cardiovascular

diseases or cirrhosis and HCC ?• The incidence and the future global burden of NASH/NAFLD

11:55-12:20



ALEXANDER WREEProfessor, Department of Hepatology and Gastroenterology, Charité Berlin, GermanyInflammasome activation in NASH - basic principle and therapeutic target

• Chronic hepatic inflammation is a hallmark in the progression of non-alcoholic steatohepatitis (NASH)

• Inflammasome cascades are over-activated in a group of NASH-patients

• NLRP3 inflammasome signaling explains key mechanisms in murine models of NASH

• Targeting the inflammasome complex using a range of novel drugs

12:20-12:45

12:20-12:45

WOLF PETER HOFMANNProfessor, Gastroenterologie am Bayerischen Platz (GBP) GermanyEstablishing a NAFLD real world cohort: Experience from Germany

Real life cohorts may help to better understand the natural history of NAFLD and to identify individuals who may benefit from future therapies. Here we present the first data from a german NAFLD real world cohort and discuss how follow up data can be used to capture clinical end points and pharmacovigilance. 12:20-13:10

50 MINUTE ROUNDTABLE DISCUSSIONS:TABLE 1: Determining clinical endpointsSTEFANO BELLENTANIIndependent Consultant Gastroenterologist and Hepatologist, Locarno, Ticino, SwitzerlandTABLE 2: Translational value of preclinical models of NAFLDRUI CASTROAssistant Professor, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, PortugalTONI VIDAL-PUIGProfessor of Molecular Nutrition and Metabolism, University of Cambridge, UK

TABLE 3: NAFLD & liver transplantationMICHAEL FUCHSProfessor of Medicine, Virginia Commonwealth University and Chief of Hepatology & Liver Transplantation, McGuire VA Medical Center, USATABLE 4: Influence of diet and lifestyle on NAFLD/NASHJOANNA DOWMANConsultant Hepatologist, Queen Alexandra Hospital, UK

STEFANO GINANNI CORRADINIAssociate Professor,Division of Gastroenterology, Department of Translational and Precision Medicine, University "Sapienza" of Rome ItalyThe role of lysosomal acid lipase activity in NAFLD/NASH pathogenesis

NASH pathogenesis is multifactorial and not completely clear. Lysosomal acid lipase (LAL) is an enzyme that hydrolyzes triglycerides and cholesteryl esters in several cells including

12:45-13:10

12:45-13:10

KARIN CONDE-KNAPECVP Global Diabetes, Cardio-renal and Translational Research, Novo Nordisk, DenmarkAnti-inflammatory/anti-fibrotic mechanisms for the treatment of NASH

• Brief overview of anti-inflammatory/antifibrotic MOA for the treatment of NASH

• Clinical vs preclinical data• Are preclinical models predictive at all for these MOA?

WILLIAM ALAZAWIReader & Consultant in Hepatology, Barts Liver Centre, Queen Mary University of London, UKWhat we can learn from large primary care databases

• Combining the healthcare records of 18 million European adults to gain insight into the epidemiology of NAFLD and NASH diagnoses in primary care.

• Diabetes is a major risk factor for cirrhosis and liver cancer diagnoses in primary care databases.

• Does a diagnosis of NAFLD or NASH increase the risk of cardiovascular outcomes?

11:25-11:55

11:25-11:55

Continued

the cardiovascular space that can also be applied to the hepatic endpoint. This presentation will discuss adjudication rationale and history, current best practices, and examples.

11:25-11:55

our targeted messaging and outreach campaigns. Qualified subjects are referred to our global site network for trial enrolment. Our Dedicated Research Sites (DRSs) have the capacity and resource to achieve high volume pre-screening. Combining fibroscan and blood tests AES can successfully identify those patients most likely to have NASH thereby accelerating recruitment to NASH trials.

hepatocytes, Kupffer cells, bone marrow-derived monocyte-macrophages and platelets. Recent data suggest that transcriptional or post-transcriptional reductions of LAL activity in blood have relevance for the pathogenesis of NASH.

12:45-13:10

12:20-13:10

12:45-13:10

Continued



13:10-14:10 Lunch

TABLE 5: Best practices for detecting, assessing and managing suspected drug-induced liver injury signals during NASH clinical trialsMELISSA PALMERCEO Liver Consulting; Former Head of Liver Disease Development, TakedaContinued

14:10-14:35

PANEL DISCUSSIONS:Combination Therapies

NIKOLAI NAOUMOV (Moderator)Executive Director, Hepatology Science and Innovation, Novartis, Switzerland

ELIAS PAPATHEODOROUCEO, Genkyotex, Switzerland



EDUARDO BRUNO MARTINSVice President, Clinical Development, Allergan

14:10-15:00

SEBASTIEN BOLZEExecutive Vice President, Non Clinical Development, Co-Founder, PoxelThe Poxel NASH portfolio: PXL770 and PXL065 two Differentiated Drug Candidates with Complementary Mechanisms of Action for the Treatment of NASH

PXL770: orally available first-in-class product targeting adenosine monophosphate-activated protein kinase (AMPK). Through its unique mechanism of action that directly activates AMPK, PXL770 acts on a very important biological target. This target, which plays a key role as a master regulator of cellular energy, has the potential to treat several chronic metabolic diseases, including diseases that affect the liver, such as NASH. PXL770 entered a Phase 2a proof-of-concept program for the treatment of NASH in early April 2019 with results expected in the second quarter of 2020. PXL065: (deuterium-stabilized R-pioglitazone), a mitochondrial pyruvate carrier (MPC) inhibitor, completed its Phase 1b development. Based upon preclinical and Phase 1 results, PXL065 is expected to exhibit a better therapeutic profile than pioglitazone for NASH, including efficacy with reduced side effects, such as those associated with the activation of gamma receptors activated by peroxisome proliferators (PPAR-γ) (weight gain, fractures and fluid retention). Phase 2 will be initiated in H2 2020.

14:10-14:35

ULF RISÉRUSAssociate Professor in clinical nutrition, Head of Clinical Research Unit, Uppsala University, Sweden Role of diet in the treatment of NAFLD• The influence of modulating the amount of fat and carbohydrates in the diet

• The influence of type dietary fatty acids on liver fat content – new lessons from trials

• Optimal diet for prevention of NAFLD and NASH?

Chair: Rebecca Taub Chief Medical Officer and President, Research & Development, Madrigal Pharmaceuticals, USA

Chair: Gautam Mehta Principal Investigator, Foundation for Liver Research

Chair: Fawaz Alzaïd Research Associate, Immunity and Metabolism of Diabetes, Cordeliers Research Centre, INSERM

14:35-15:00

REBECCA TAUBChief Medical Officer and President, Research & Development, Madrigal Pharmaceuticals, USAResmetirom, a highly beta selective liver-directed thyroid hormone receptor beta agonist for the treatment of NASH

• Potential of thyroid hormone receptor beta agonist in NASH, Phase 2 data

• Phase 3 MAESTRO-NASH for the treatment of NASH and advanced fibrosis

• Phase 3 MAESTRO-NAFLD, safety and non-invasive NASH and lipid biomarker data including reduction of atherogenic

14:35-15:00

ANGELA SLITTPrincipal Investigator (Basic Researcher), Spanish National Research Council and CIBERDEMIs Environmental Exposure a Risk Factor for Hepatic Steatosis?

Obesity, diabetes, and insulin resistance are all risk factors associated with the development of hepatic steatosis and non-alcoholic fatty liver disease (NAFLD). The contribution of environmental exposures as risk factors for fatty liver disease is not well known. The presentation will provide two examples of environmental exposures that are associated with hepatic steatosis. Bisphenol A (BPA) is a weak estrogen and



15:00-15:25

HAROLD H. SHLEVINPresident and Chief Executive Officer, Galectin Therapeutics Inc. USA (NASDAQ:GALT)Clinical development of belapectin (GR-MD-02), a galectin-3 inhibitor, in treatment of NASH cirrhosis

Galectin-3 inhibition has been shown to be central to the fibrotic process. NASH related cirrhosis represents an area of high unmet medical need and is rapidly becoming the number one reason for liver transplants. Belapectin (GR-MD-02), a galectin-3 inhibitor, has been demonstrated to decrease hepatic venous pressure gradient in compensated NASH cirrhotic patients without varices at baseline. We will discuss how results of our Phase 2 study have helped to inform the design of a phase 3 trial. The phase 3 trial uses minimally invasive endpoints common in clinical practice to select patients with portal hypertension at risk of developing varices and is optimized for patient enrollment and retention over a 2 year duration of treatment.

15:00-15:25

15:00-15:25

MICHAEL FUCHSProfessor of Medicine, Virginia Commonwealth University and Chief of Hepatology & Liver Transplantation, McGuire VA Medical Center, USANovel serum biomarkers mirroring the transition from steatosis to steatohepatitis

• Linking oxysterols to insulin resistance and inflammasome activation

• Identification of new NASH serum biomarkers and Cyp7b1 as new target for NASH drug development

Continued

RUI CASTROAssistant Professor, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, PortugalInter-organ crosstalk in NAFLD

NAFLD highly associates with components of the metabolic syndrome, such as obesity and type II diabetes, two of the best characterized NAFLD risk factors. In fact, NAFLD is a complex and multifactorial disease, and its pathogenesis also involves the adipose tissue, skeletal muscle and gut, in a bilateral crosstalk. As such, NAFLD triggering and progression remains incompletely understood, particularly regarding the signaling mechanisms responsible for disruption of extra-hepatic homeostasis.

14:10-15:00

14:35-15:00

lipids and lipoproteins in patients with NASH (biopsy) and presumed NASH (non-invasive diagnosis)

14:35-15:00

reproductive, developmental, and systemic toxicant in animals that is present in polycarbonate plastics. Concerns for BPA exposure are centered around endocrine disruption and early in life exposure. Our studies indicate that developmental BPA exposure induced hepatic steatosis in mice in adulthood, which was associated with alterations in gene expression. A second example is Per and polyfluoroalkyl substances (PFASs), which are are a group of man-made chemicals that can be found in food packaging, stain repellent fabrics, and non-stick products. PFOS, PFOA, PFNA, and PFHxS are known to have multiple adverse liver effects in rodents and have been detected in human liver biopsy samples. Our presentation will summarize the findings of several studies we have conducted with various diet combinations and human hepatocyte models to understand the lipogenic potential of PFASs for human liver.

15:25-15:50

HUBERT CHENChief Medical Officer, MetacrineSustained FXR agonist as optimized, best-in-class treatment for NASHActivating farnesoid X receptor (FXR) has been

clinically validated to improve non-alcoholic steatohepatitis (NASH) and fibrosis, although common drawbacks include increased low-density lipoprotein cholesterol (LDL-C) and moderate-severe pruritus within the therapeutic dose range. Recently, transient non-bile acid FXR agonists have shown limited efficacy with once-daily dosing, likely due to suboptimal target engagement. Sustained FXR agonist with a novel non-bile acid structure and enhanced potency, such

15:25-15:50

MELISSA PALMERCEO Liver Consulting ; Former Head of Liver Disease Development, TakedaBest practices for detecting, assessing and managing suspected drug-induced liver injury signals during NASH clinical trials

• The last decade has seen a rapid growth in the number of clinical trials enrolling patients with NAFLD and NASH. Patients with NASH often require different approaches to the assessment and management of suspected drug induced liver injury (DILI) compared to patients with healthy livers.

• Currently no regulatory guidelines or position papers

15:25-15:50

CHRIS BYRNEProfessor Endocrinology & Metabolism, Human Development and Health Academic Unit, Faculty of Medicine, The \Institute of Developmental Sciences (IDS), University of Southampton, UK

Diabetes and NAFLD: a vicious spiral affecting both diseases• Risk of diabetes with NAFLD• Worsening insulin resistance and glycaemic control with

NAFLD affecting diabetes treatments • Diabetes management with end stage liver disease.


15:50 Conference Close


15:25-15:50

as Metacrine’s MET409, has demonstrated prolonged FXR engagement and an encouraging safety and tolerability profile – including a lack of adverse impact on LDL-C levels – in early clinical trials. These results demonstrate the potential of sustained FXR agonism to deliver a differentiated, best-in-class profile.

15:25-15:50

systematically address best practices pertaining to DILI in NASH clinical trials.

• Recommended best practices pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, DILI detection, approach to a suspected DILI signal, causality assessment and hepatic discontinuation rules will be discussed.

15:25-15:50

Continued

DAY 2: 50 MINUTE ROUNDTABLE DISCUSSIONS:TABLE 1: Determining clinical endpointsSTEFANO BELLENTANIIndependent Consultant Gastroenterologist and Hepatologist, Locarno, Ticino, Switzerland• How to reach the diagnosis of NASH in people with NAFLD:

always invasive procedure (liver biopsy) or not?• Which would be the endpoint of therapy: stop of the inflammation

process? stop of the fibrosis evolution? Both? Which first and how to reach these objectives?

• Is surveillance of all the patients with NASH necessary for the prevention of HCC? Which patients we should put on a surveillance program?

• Do we have now all the tools to identify patients whit NASH who will develop Cardiovascular Disease (CVD)?

• Which patients with NASH need genetic screening and strict monitoring to avoid progression to either HCC or CVD?

TABLE 2: Translational value of preclinical models of NAFLDRUI CASTROAssistant Professor, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Portugal

TONI VIDAL-PUIGProfessor of Molecular Nutrition and Metabolism, University of Cambridge, UKThere is an explicit need for a “ideal” NAFLD/NASH model for use in preclinical drug development. Most in vivo studies use mouse models owing to their relatively low cost, short lifespan and ease of genetic manipulation, which allow for a level of experimental control that is not possible with human studies. Despite several animal models attempting to mirror the histopathology and pathophysiology of each stage of human NAFLD, including development of fibrosis or even HCC, no current model can simultaneously reproduce all major features of severe human NASH. As such, researchers should focus on particular aspects of the disease and, accordingly, choose

the most appropriate model. Still, and to concur with the Animal Research: Reporting of In Vivo Experiments (ARRIVE) criteria, minimum requirements for models of NASH should be set. But which are these requirements? Should the focus be put solely on the liver? How does the translational value of genetic and dietary animal models compare? Could it be advantageous to use more than one model? These are some of the aspects that will be discussed.

TABLE 3: NAFLD & liver transplantationMICHAEL FUCHSProfessor of Medicine, Virginia Commonwealth University and Chief of Hepatology & Liver Transplantation, McGuire VA Medical Center, USANonalcoholic steatohepatitis (NASH) is the fastest-growing indication for liver transplantation and a leading cause of hepatocellular carcinoma among patients listed for liver transplantation in the United States. NASH poses a significant challenge in both pre- and post-transplant period due to its association with metabolic syndrome as well as cardiovascular and chronic kidney disease. In the absence of FDA-approved pharmacotherapy, life-style interventions and optimizing of risk factors remains the mainstay of therapy. Some of the many challenges in the field include:Pre-Transplant:• What is the optimal strategy to assess cardiovascular risk?• Should treatment of risk factors for NASH be different in patients

on the transplant wait list?Post-transplant:• What is a reasonable strategy to identify NASH recurrence or de

novo NASH?• What is the role of immunosuppressive drugs in post-transplant

NASH?• What is the optimal strategy to address weight gain?• Are FDA-approved drugs for NASH in the pre-transplant setting

also suitable after transplant?• Should a different regulatory pathway for NASH drugs apply in the

post-transplant setting?

TABLE 4: Influence of diet and lifestyle on NAFLD/NASHJOANNA DOWMANConsultant Hepatologist, Queen Alexandra Hospital, UK• Optimal dietary recommendations for patients with NASH• What are the hepatic and extra-hepatic benefits of physical activity

in NASH, and what exercise should we recommend?• Barriers to lifestyle modification from both the HCP and patient

perspective, and how can we enhance patient motivation and engagement?

• In the approaching era of licensed drug therapies for NASH, how can medication be promoted as complimentary to, rather than a replacement for, lifestyle modification?

TABLE 5: Best practices for detecting, assessing and managing suspected drug-induced liver injury signals during NASH clinical trialsMELISSA PALMERCEO Liver Consulting ; Former Head of Liver Disease Development, TakedaThe last decade has seen a rapid growth in the number of clinical trials evaluating novel molecules with a variety of mechanisms of action targeted to treat NASH. Due to the underlying chronic liver disease, patients with NASH require different approaches to the assessment and management of the new onset of elevated liver-related blood tests and suspected drug-induced liver injury (DILI) compared to patients with healthy livers. Topics for discussion will include:• Are patients with NASH at increased risk for DILI?• Hepatic eligibility criteria• Monitoring if liver tests during NASH clinical trials• Assessment of DILI risk during NASH drug development • Hepatic discontinuation rules• Monitoring and assessment of DILI during clinical trials of

compensated and decompensated cirrhotic patients with NASH• Seladelpar histology results– What does this mean for NASH

clinical development?

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SPONSORSHIP AND EXHIBITION OPPORTUNITIES AVAILABLEFor more details contact Faizel Ismail/Tony Couch at:

[email protected] or call +44 (0) 1865 849841

DON’T DELAY, BOOK YOUR PLACE TODAY!Places are limited and are based on a first come, first served basis so to avoid disappointment contact us today

to reserve your place at Global Engage’s 3rd Global NASH Congress 2020 and co-located Metabolic Syndrome, Diabetes and NAFLD Symposium on the 10th-11th February 2020.

PHONE BOOKING+44 (0) 1865 671957 ext. [email protected]

Our conference team will make all the necessary arrangements.

ONLINE BOOKINGVisit the website to book your place

www.global-engage.com/event/nash

THE CONGRESS PACKAGE INCLUDES:All Conference Sessions

Lunches and RefreshmentsAccess to Exhibition Room

Networking Drinks ReceptionConference Workbook

E-Document Pack

HOTEL ACCOMMODATIONHotel accommodation will be available at a group rate.

FREE NEWSLETTERFor updates on the 3rd Global NASH Congress 2020 and co-located Metabolic Syndrome, Diabetes and

NAFLD Symposium, plus free resources and reports, as and when our speakers authorise their release dates, check for updates at: www.global-engage.com/event/nash

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3rd global nash congress 2020 metabolic syndrome … · warm welcome 3rd global nash congress 2020...

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