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April 22-25, 2019 | Boston, MA

57 Expert Speakers ♦ 4 Days  3 Streams ♦ 4 Workshops  Seminar Day ♦ 15+ Hours of Networking

Day One
Tuesday April 23

Day Two
Wednesday April 24

07.50
Chair’s Opening Remarks

  • Laurent Fischer Senior Vice President, Head Liver Therapeutic Area Allergan

Outlining Current Understanding & Gaps in Our Knowledge to Most Efficaciously Address NASH

08.00
What is the Future of NASH?

  • Laurent Fischer Senior Vice President, Head Liver Therapeutic Area Allergan

Synopsis

Overviewing areas of unmet need with emphasis on unchartered territory and addressing the associated high priority questions limiting drug development in these spaces including:

  • Collaboration in NASH. How do we partner to advance the field?
  • How do we meet the urgency of identifying biomarkers to diagnose patients with NASH and fibrosis at risk of disease progression?
  • What can we expect from different agents targeting steatohepatitis and/or fibrosis?
  • Are current surrogate endpoints aligned with stakeholders’ expectations?
  • Are combinations and cross-company collaborations the future of NASH therapy?

08.30
Keynote: Many Paths to NASH-Many Targets for Treatment

  • Brent Tetri Director, Division of Gastroenterology & Hepatology; Professor of Internal Medicine , Saint Louis University School of Medicine

Synopsis

  • NASH is a phenotype that likely results from different genetic, epigenetic and dietary exposures in different patients
  • The underlying driver of hepatocellular injury and the resulting inflammation and fibrosis in NASH is an oversupply of fatty acids in hepatocytes
  • Approaches to treatment include interventions that reduce energy intake, improve extrahepatic metabolism of fatty acids and glucose, decrease the generation of fatty acids in the liver, reduce the inflammatory wound response caused by lipotoxicity and reverse extracellular matrix deposition
  • As new drugs are developed, future therapy for NASH will likely involve a multi-drug approach in addition to lifestyle modification that is rationally based on complementary pathways

09.00
Session Reserved for ICON

10.00
Speed Networking

10.45
Morning Break

Cross-Disciplinary Outlook on NASH Molecular Drivers & Targeting Them

11.30 An Analysis of NASH Pathways by Single Cell Sequencing

  • NASH develops through an interplay of several cell types in the liver which exist in varying abundances, although the precise nature of these interactions remains unknown
  • Single Cell Sequencing (SCS) advances the sequencing capabilities of RNAseq by providing quantifiable RNA transcript reads on a single-cell basis
  • By applying SCS technology to NASH and healthy liver samples, an understanding of cell-specific biology can be achieved as it relates
    to the pathological features of NASH

James Conway
Senior Scientist- Translational
Bioinformatics
MedImmune

12.00 Preclinical to Clinical Translation: Critically Review Quantification Methods of Liver Fat Oxidation as well as Protein Flux Biomarkers

• Exploring proteomic methods for a dynamic measurement of physiologic function and confidently quantify liver fat oxidation
• Reviewing recent progress in protein flux biomarkers as a noninvasive diagnostic
• Implementing quantification methods of liver fat oxidation and protein flux biomarkers to improve development from preclinical to clinical translation

Stephen Previs
Director
Merck

12.30 Targeting Multiple Drivers of NASH by GSNOR Inhibition: Inflammation, Oxidative Stress, Steatosis, Glucose Dysregulation, & Fibrosis

• Regulating cellular nitrosylation through GSNOR inhibition and therefore inhibiting many drivers of pathology
• Demonstrating efficacy of SAJE’s small molecule GSNOR inhibitor
• Evaluating the potential to prevent progression of NASH and, perhaps, to reverse it, and obviate the need for multiple drugs to regulate the disease

Matthews Bradley
Founder, Chairman, President &
Chief Technical Officer
SAJE Pharma

Investigating New Targets & Confirming Rationale in Human Context

11.30 Use of Precision Cut Liver Slices in the Modelling of Fibrosis

  • Demonstrating the utility of precision cut liver slices (PCLS) retaining the structure and cellular composition of the native liver and therefore representing a much superior and improved system to study liver fibrosis compared to twodimensional or mono/co-cultures of cells
  • Showcasing the Newcastle Fibrosis Research Laboratory (NFRG) bioreactor system that increases the healthy lifespan of PCLS which allows us to model fibrogenesis
  • Sharing data on testing the ability of clinically approved drugs to limit fibrosis in this model; as an example, nintedanib and obeticholic acid therapy limit fibrogenesis in PCLS
  • Describing how this new bioreactor can be successfully used to model fibrogenesis and demonstrate efficacy of anti-fibrotic therapies

Jelena Mann
Professor of Epigenetics
Fibrosis Research Group
Newcastle University

12.00 HepaStem for the Treatment of Fibro-Inflammatory Liver Diseases

  • Showing Hepastem as having multiple MoA of interest for NASH
  • Presenting clinical data generated in ACLF patients
  • HepaStem is developed in NASH indication (PhI/IIa)

Etienne Sokal
Chief Scientific & Medical Officer
Promethera Biosciences

12.30 Anti-inflammatory & Anti- Fibrotic Effects of Icosabutate, a Structurally Engineered Fatty Acid, in Differentiated Rodent NASH Model

  • Outlining the rationale behind structurally engineering of fatty acids for the treatment of liver disease
  • Showcasing ADME properties of icosabutate
  • Demonstrating the effects of icosabutate om inflammation and fibrosis in diverse rodent NASH models
  • Sharing insights into mechanism/s of action

David Fraser
Chief Scientific Officer
NorthSea Therapeutics

Strategic Oversights for Phase 3 Clinical Trials

11.30 NASH, Now: Therapeutic Targets & the Competitive Clinical Trial Landscape

  • Overview of clinical compounds being evaluated for NASH with emphasis on mechanistic differences
  • Evaluating regulatory guidance on development of NASH therapeutics with focus on histology versus non-invasive imaging in drug advancement
  • Discussing how current clinical experience and understanding can influence the next generation of R&D and commercialization decisions

Peter Traber
Partner
Alacrita Consulting

12.00 NASH Clinical Trial Design with Emphasis on Patient Recruitment

• Overview of study design for phase 3 NASH clinical trials
• Strategic considerations for patient recruitment in phase 3 trials

Star Seyedkazemi
Associate Vice President in Clinical Development
Allergan

Optimizing Clinical Trial Design to More Confidently Reflect Clinical Outcome

12.30 The HepQuant Tests as Aids to Drug Development

  • HepQuant tests (HepQuant SHUNT, HepQuant FLOW, HepQuant STAT) are blood-based and minimally invasive
  • The tests yield a disease severity index (DSI) of the liver’s health
  • STAT has favorable characteristics for use in pre-screening cases for trials
  • SHUNT has favorable characteristics for tracking disease progression or response to treatment
  • There are clinically significant cutoffs for DSI

Greg Everson
Chief Executive Officer
HepQuant

13.00
Lunch & Networking – Lunch Seminar Hosted By: High Point Clinical Trials Center

Case Studies of Emerging Candidates

14.00 Tissue-Specific Integrin Modulation & EMT Inhibition For The Treatment of NASH

  • Pliant Therapeutics focuses on developing small molecules to selectively target transcriptional regulation of epithelial-tomesenchymal-
    transition (EMT), a process that is induced by TGF-β
  • By selectively targeting EMT, Pliant aims to target many fibrotic diseases through novel mechanisms

Éric Lefebvre,
Chief Medical Officer
Pliant Therapeutics

14.30 CSTI-100, a Melanin- Concentrating Hormone Receptor 1 (MCHR1) Antagonist, for the Treatment of NASH and Metabolic Syndrome Comorbidities

CSTI-100, a selective MCHR1 antagonist addresses hallmark NASH symptoms and important related metabolic syndrome comorbidities.
In preclinical models of NASH, CSTI- 100 demonstrates:

  • Reductions in liver triglycerides, non-esterified fatty acids and cholesterol
  • Reductions in key liver inflammatory, fibrosis and injury biomarkers
  • Fat selective weight loss due to a reduction in food intake
  • Improvements in glucose tolerance and insulin sensitivity

Peter Guzzo
Cofounder & Chief Executive Officer
ConSynance Therapeutics

Critically Addressing the Bench to Bedside Translational Gap

14.00 Using Antisense Oligonucleotides for Treatment of NASH

• Demonstrating antisense inhibition of Angptl3 as a NASH therapeutic in animal studies
• Demonstrating antisense inhibition of Keap1 as an anti-oxidant NASH therapeutic in animal studies

Richard Lee
Director
Ionis Pharmaceuticals

14.30 Methionine Aminopeptidase 2 Inhibitors as Novel Agents for Treatment of NAFLD/NASH

• Introducing MetAP2 in the context of NASH
• Showcasing efficacy in animal models of NAFLD/NASH
• Presenting clinical experience to date and translation from bench to bedside

Bryan Burkey
Head of Pharmacology
Zafgen

Optimizing Clinical Trial Design to More Confidently Reflect Clinical Outcome (Continued)

14.00 Machine Learning for Patient Selection

  • Harnessing innovations in machine learning to identify and characterize NASH patients for more confident enrichment of clinical trial populations

Anthony Samir
Assistant Professor
Harvard Medical School

14.30 Adhering to Regulatory Guidelines & Overcoming Clinical Challenges Related to NASH Proof of Concept Studies

  • Filling the gap between noninvasive assessment of NASH PoC endpoints and the clinically relevant endpoints
  • Robustly applying non-invasive MRI imaging in addition to liver fat quantification
  • Revewing in silico trial simulations using 10,000 virtual NASH patients to explore and support diverse study designs
  • Are there more relevant and helpful approaches in the European vs. North American current thinking in the moving target NASH development field?

Pietro Scalfaro
Chief Medical Officer
Enyo Pharma

15.00
Afternoon Refreshments & Networking

Innovations in Ex Vivo & Biomarkers to More Confidently Monitor Drug Efficacy

16.00
Using 3D Bioprinted Human Liver Tissue to Model NAFLD/NASH in vitro?

  • Jeff Irelan Director, Scientific Application , Organovo

Synopsis

  • ExVive™ Human Liver Tissue is an in vitro 3D bioprinted liver model containing primary human hepatocytes, hepatic stellate cells, endothelial cells, and Kupffer cells, with a complex multicellular architecture and sustained function and viability (at least 4 weeks in culture)
  • Nutrient overload by addition of excess fatty acids and sugars leads to steatosis in the model, which when combined with an inflammatory stimulus can progress to hepatocellular injury, inflammation and fibrosis, characteristic of NASH
  • Together, these features suggest that 3D liver tissues hold promise for the study of complex, chronic conditions such as NASH, enabling the discovery of novel therapeutics, biomarkers, and safety assessment of drugs in a disease-relevant background

16.10
An Atypical Biomarker Story – Discovery and Evolution of the Enhanced Liver Fibrosis (ELFTM) Test

Synopsis

  • Learn about of liver fibrosis blood based biomarker panels and their differences.
  • Lessons learned from the discovery and development of the ELF test.
  • How the ELF test is being used today in trials and the clinic.

Counting on Combo: Investigating Pharmacotherapy to Address NASH as a Complex Pathophysiology

16.40
How Do We Address Fibrosis More Effectively?

  • Bryan Fuchs Assistant in Molecular Biology , Massachusetts General Hospital

Synopsis

  • Overcoming increased challenges associated with developing two novel entities together
  • Identifying fibrosis and cirrhosis patients at high-risk for Hepatocellular Carcinoma

17.10
Critically Reviewing Which Mechanisms of Action to Combine to Address NASH

  • Nikolai Naoumov Executive Director, Hepatology Sciences & Innovation , Novartis

Synopsis

  • Understanding the rationale for combination regimes in NASH
  • Exploring combination options in clinical studies and the success of combination development so far

17.40
Chairs’ Closing Remarks

18.00
Scientific Poster Session