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May 4-6, 2020 | Boston, MA

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
Strategies for Patient Identification, Access & Site Engagement in NASH Trials

Synopsis

  • Outlining ICON’s pre-screening strategy to respond to increased competition for NASH patients, coupled with high screen failure rates associated with this indication
  • Discussing the details of the methodology and best practices of the pre-screening effort, together with potential areas for future focus

09.30
Speed Networking

10.15
Morning Break

Cross-Disciplinary Outlook on NASH Molecular Drivers & Targeting Them

10.45 Targeting the Wnt Pathway

• Proving liver fibrosis is the most important histological feature that is associated with long term outcomes of NASH patients
• Targeting the Wnt signaling pathway could potentially provide an important therapeutic intervention for liver fibrosis

Weilin Xie
Senior Principal Scientist
Celgene

11.15 Rationale for the Use of Bile Acid Modulators for the Treatment of NASH

• Demonstrating preclinical data of bile acid modulators
• Reviewing literature and presenting an argument for the use of bile acid modulators against NASH

Patrick Horn
Chief Medical Officer
Albireo Pharma

11.45 Talk details to be finalized

Critically Addressing the Bench to Bedside Translational Gap

10.45 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

11.15 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)

Nathalie Belmonte
Vice President Product Development
Promethera Bioscience

11.45 Utility of an Accelerated Translational Model of NASH: FATZO Mouse Induced with High Fat Diet and CCl4

• Presenting a new NASH model with accelerated disease progression & exacerbated pathology
• Characterization of model and improved outcome with obeticholic acid treatment
• Demonstrating utility of new model for preclinical NASH studies

Guodong Zhang
Director of Crown Bioscience
Louisiana (CBLA)
Crown Bioscience

12.00 NASH - Fibrosis & Beyond

• Recapitulating fibrosis as a key hallmark of progressive liver disease and asking the question: what it means health wise?
• Understanding how we monitoring for progression to HCC in vivo

Michael Briggs
President & Chief Scientific Officer
Woodland Biosciences

Strategic Oversights for Phase 3 Clinical Trials

10.45 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

11.15 Does Recruitment in NASH Trials Have to Behave like a Rare Disease?

• Exploring the trend and root causes of the NASH patient recruitment decline
• Initiating a conversation on the nearterm and potential long term future of the large trials and the recruitment in them
• Analyzing the possible impacts of the first histological readouts from the current Phase 3 trials and the FDA decision on the use of surrogate markers for dual liver biopsies
• Examining ideas for the engagement of the ultimate payers into the recruitment process: the PCPs and non-hepatology specialists

Robert Riccio
Vice President, Clinical Development

Alastair Smith
Executive Medical Director
Syneos Health

11.45 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

12.15
Lunch & Networking – Lunch Seminar Hosted By: High Point Clinical Trials Center

Cross-Disciplinary Outlook on NASH Molecular Drivers & Targeting Them (Continued)

13.15 Targeting Alpha V Integrins for Liver Fibrosis

• Anti-fibrotic treatment represents an unmet medical need for patients with fibrosis diseases, such as NASH, kidney fibrosis, and IPF
• Alpha V integrins are membrane proteins that bind to latencyassociated peptide (LAP) of TGF-β as its principal ligands and activate mature TGF-β to lead to fibrogenesis
• Morphic Therapeutic is leading the development of a new generation of oral drugs to target alpha V integrins for fibrotic disorders

Min Lu
Director, Head of Fibrosis
Morphic Therapeutics

Case Studies of Emerging Candidates

13.45 Targeting Integrin αVβ1 For The Treatment of Liver Fibrosis Associated With NASH

  • Integrin receptors regulate multiple processes involved in inflammation, cell adhesion and fibrosis
  • Av integrins are of interest as antifibrotic targets due to their role in cell-specific TGFb activation and promotion of fibrosis
  • Selective targeting of specific integrins with small molecule inhibitors can interrupt the pro-fibrotic TGFb pathway, without the risks associated with systemic TGFb inhibition
  • Pliant have developed oral small molecule integrin inhibitors with demonstrated antifibrotic activity in primary human liver tissue slices and preclinical models of liver fibrosis

Éric Lefebvre,
Chief Medical Officer
Pliant Therapeutics

14.15 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, nonesterified 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

14.45 ROCK2 Inhibitors for the Treatment of NASH

  • ROCK2 is often upregulated in diseases associated with acute and chronic inflammation, including those associated with damage caused by high glucose and high fat diets.
  • Highy selective ROCK2 inhibitors developed by Redx scientists have demonstrated both anti-fibrotic and anti-inflammatory activity in preclinical in vitro and in vivo models of fibrosis.

Nicolas Guisot
Research Fellow
Redx Pharma

Investigating New Targets & Confirming Rationale in Human Context

13.15 Diet-Induced NHP Models of NASH & Fibrosis

Tony Wang
Chief Technology Officer
Kunming Biomed International

13.45 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

14.15 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

14.45 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 Considerations for Phase 3 Clinical

1.15 Role of Metabolomics in NASH Clinical Trials: A Proposal From BARC Lab/OWL

  • How to provide full lab services in NASH-related clinical trials
  • Strengths & Limitations of Metabolomics
  • Case Study
  • Looking for NASH subtyping

Optimizing Clinical Trial Design to More Confidently Reflect Clinical Outcome

13.45 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

14.15 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

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

  • Filling the gap between non-invasive 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

15.15
Afternoon Refreshments & Networking

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

16.20
Using 3D Bioprinted Human Liver Tissue to Model NAFLD/NASH in vitro?

  • Kelsey Retting Associate Director, Tissue Platform Operations , 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

16.30
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

17.00
Kill two birds with one stone: MRI-1867, hybrid inhibitor of peripheral cannabinoid receptor 1 (CB1R) & inducible nitric oxide synthase (iNOS), for the treatment of NASH & liver fibrosis

  • Resat Cinar Co-Chair NIH Fibrosis Scientific Interest Group , National Institutes of Health

Synopsis

  • Outlining rationale for multi-target approach by polypharmacology to develop effective therapies in complex progressive diseases such as NASH and fibrotic diseases.
  • Identifying dual targeting of peripheral cannabinoid receptor 1 (CB1R) & inducible nitric oxide synthase (iNOS) as an effective therapeutic strategy in obesity, diabetes, AFLD, NAFLD, NASH and liver fibrosis
  • Introducing the concept of third-generation cannabinoid receptor 1 (CB1R) antagonists for metabolic and fibrotic disorders.
  • Demonstrating preclinical efficacy of MRI-1867, an orally bioavailable small moleculeantagonist  of peripheral CB1R/iNOS, in liver fibrosis.

17.30
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

18.00
Talk details to be finalized

18.30
Chairs’ Closing Remarks

18.45
Scientific Poster Session