*All times Eastern Standard Time*

Deep Diving into 2021’s Most Pivotal NASH Drug Development Research

7:30 am Registration & Networking

8:00 am Discovering How the Sexually Dimorphic Nature of NASH May Impact Disease Progression & Drug Responses

Synopsis

• Discovering why NASH is sexually dimorphic and learning what this means from a drug development perspective
• Investigating different diagnostic tools that can be utilized to successfully consider sex differences
• Deep diving into different pharmacological approaches which may give rise to different sex, different responses

8:30 am NASH: What is Next After Metabolic Improvement?

  • Alessandro Pocai Senior Director for Cardiovascular & Metabolic Research, Janssen

Synopsis

• Focusing on target discovery and precision medicine
• Outlining a high-level overview landscape with promising therapies currently in development
• Hearing what’s next for Janssen’s in the context of target discovery and precision medicine

9:00 am Weight Loss— The Preferred Treatment for NASH

Synopsis

• Bariatric and epidemiologic studies provide compelling evidence that weight loss is the preferred treatment option for NASH and its co-morbidities
• GLP-1 based agents and dual agonists have achieved sufficient weight loss in clinical trials to drive potent reductions in liver fat reduction and NASH inflammation, but further evidence is needed to demonstrate meaningful effects on NASH fibrosis
• Tolerability due to GI side effects remains a barrier to the use of GLP-1 based agents

9:30 am A NASH Drug Development Landscape Post-mortem: Critically Analyzing Lessons Learned from the Past 12 Months of NASH Drug Development Failures to Understand How to Avoid Common Mistakes & Achieve Clinical Success in 2022 & Beyond

  • Bart Staels Professor, University of Lille
  • Becky Taub Founder, Director, CEO & President, Madrigal Pharmaceuticals
  • Ashwani Singal Professor of Medicine, University of South Dakota Sanford
  • Stephen Rossi Chief Development Officer, Northsea Therapeutics

Synopsis

• Discussing key NASH drug development updates from the past 12 months
• Reflecting on recent failures in NASH drug development to discern what went wrong and understanding how to mitigate for similar faults
• Setting yourself up for success: What steps must you take to maximize your chances of achieving clinical success in 2022

10:00 am Speed Networking

10:30 am Morning Break & Networking

Discovery

Exploring Novel Targets for NASH Drug Development

11:00 am Discovery of TERN-501, a Selective THR-Agonist for the Treatment of Non- Alcoholic Steatohepatitis

Synopsis

• Learning about TERN-501: A liver-distributed, highly selective agonist of thyroid hormone receptor beta (THR-b)
• Discovering how TERN-501 has been designed to be metabolically stable to reduce pharmacokinetic variability, allowing for a low clinical dose and potential use in a fixeddose combination
• Hearing how TERN-501 significantly improves lipid parameters and reduces steatosis in preclinical models of hypercholesteremia and NASH

11:30 am Inflammasomes & Downstream Signalling as Novel Targets for Fibrotic NASH

Synopsis

• Describing experimental and human evidence for the role of inflammasome pathways in fibrotic NASH development
• Reviewing mechanisms of NLRP3 driven hepatic stellate cells activation
• Dissecting novel downstream signals including IL-18 and caspase 1 dependent pyroptotic cell death in liver fibrosis

12:00 pm 3D microscopic imaging and machine learning quantification of liver fibrosis

Synopsis

• Describe the technology behind 3D pathology
• Understand the advantages of 3D vs 2D pathology
• List the ways in which 3D pathology can accelerate drug development and improve clinical readouts in NASH-related fibrosis.

Translational

Closing the Translational Gap: Update on NASH Models

11:00 am Harnessing the Power of Preclinical NASH Models to Strategically Predict & Improve Clinical Outcomes & Therapeutic Response

  • James Trevaskis Senior Director of Biology & Head of Fibrosis Research, Gilead

Synopsis

• Highlighting preclinical rodent models of NASH and liver fibrosis, and ex vivo/in vitro systems modeling aspects of NASH/fibrosis.
• Illustrating predictive capacity of preclinical models/systems to clinical efficacy by discussing ACC inhibitor/FXR agonism combination approach. • Investigating how to optimize preclinical NASH model use to strategically achieve a positive therapeutic response

11:30 am Investigating the Tropifexor Mechanism of Action & Treatment Outcomes with a Disease Model of NAFLD/NASH

Synopsis

• Investigating the mechanism of action of tropifexor
• Representing a clinical trial population with a virtual population
• Identifying which patient populations may most benefit from tropifexor

12:00 pm Translational NASH Drug Development

Synopsis

• Discussing the recent progress of KBI’s unique NHP NASH/fibrosis model in close association with metabolic dysregulations
• Exploring non-invasive imaging technologies for NASH and for improving detection of early stages of liver fibrosis

Clinical

Uncovering the Latest Clinical NASH Research

11:00 am Results of a Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability & Pharmacodynamics of the Fructokinase Inhibitor PF-06835919 Administered Daily for 16 Weeks in Adults with NAFLD & T2DM

Synopsis

• Revealing results of nonclinical studies and a prior 6-week clinical study in patients with NALFD suggest that the orally administered fructokinase inhibitor PF-06835919 may have the potential to lower liver fat content and improve markers of insulin sensitivity.
• Understanding the steps taken to further assess the potential utility of PF-06835919 for the treatment of NASH and/or insulin resistance, a 16-week randomized, double blind, placebocontrolled study assessing two active doses of PF-06835919 in patients with NAFLD and T2DM was designed and conducted.
• Analyzing our study results in depth

11:30 am Tirzepatide for the Treatment of NASH

  • Axel Haupt Vice President for Diabetes Clinical Investigation & Insulin & Incretin Research, Eli Lilly

Synopsis

• Hearing how Tirzepatide shows improvement in NASH biomarkers and relevant metabolic traits in phase 2 and phase 3 trials in patients with T2D
• Revealing how Tirzepatide shows profound lowering in liver fat – a phase 3 MRI addendum in T2D
• Discovering SYNERGY-NASH: Tirzepatide Phase 2 design

12:00 pm Innovative Solution Services for Biopsy Endpoints to Optimize NASH Drug Development – A Strategic Partnership

Synopsis

• Key challenges in NASH Clinical Trials
• Specific Liver Biopsy Hurdles – Clinical Trial Example
• PathAI’s AI-based Measurement of NASH (AIM-NASH) drug development tool
• Summit and PathAI have developed an innovative offering for NASH sponsors featuring trial design, site activation and patient enrollment, wet lab, diagnostic, and AI-pathology deployment services

12:30 pm Lunch & Networking

1:30 pm Learning About the Gut- Liver Axis as a Therapeutic Target in NASH

Synopsis

• Describing the importance of the microbiome in health and disease
• Exploring possible mechanisms by which changes in the microbiome may improve NASH
• Understanding the effects of HTD1801 on human NASH – possible actions via microbiome Adrian M. Di Bisceglie, Chief Medical Officer, HighTide Therapeutics

2:00 pm Novel Target Identification & Validation Using Complex in vitro Models & Computational Biology in NASH.

  • Ryan Feaver Program Director, HemoShear Therapeutics, Inc.

Synopsis

• Capturing critical pathophysiologic drivers of NASH to recapitulate human disease in vitro
• Utilizing diverse computational biology approaches to identify novel targets
• Validating and systematically rank targets for pipeline decision-making and prioritization Ryan Feaver, Program Director, HemoShear Therapeutics

2:30 pm Reserved for BioCellvia

3:00 pm Analyzing the Varied Mechanisms of Action of Existing NASH Candidates to Compare & Contrast Their Ability to Influence Fibrosis & Inflammation in the Liver

Synopsis

• Reviewing the current landscape of NASH candidates and key mechanistic targets, discuss the importance of the combination approach.
• Focusing on targeting metabolic aspects of NASH and how reducing lipid accumulation influences downstream inflammation and fibrosis.
• Discussing Cotadutide and dual-action at GLP-1 and glucagon receptors influence multiple metabolic and liverspecific outcomes. Highlight new data.

1:00 pm Exploring the Relevance of Liver Tumors in NASH

  • Paul Monga Assistant Dean, Vice Chair & Endowed Chair of Experimental Pathology, University of Pittsburgh

Synopsis

• Determining whether there are any unique drivers of liver tumors in NASH?
• Analyzing animal models to study liver tumors
• Investigating the role of Wnt pathway in HCC

1:30 pm Closing the Gap Between Pre-Clinical Efficacy Testing & Human Clinical Trials Practices in Fibrotic NASH: The Key to Successful Translation

  • Yury Popov Division of Gastroenterology, Hepatology & Nutrition, Harvard Medical School

Synopsis

• Understanding why in diseases associated with progressive fibrosis such as NASH, there is a fundamental methodological discordance between efficacy testing in animal models of liver fibrosis and clinical trials in humans. These include treating too early and mild disease in animals and relying on “surrogate” endpoints that are not reflecting the therapeutic goal in chronic liver disease in humans.
• Exploring existing and new pre-clinical animal models should undergo continuous and systematic improvement in parallel with clinical development effort: refinement, standardization, optimization, and “humanization” of efficacy end-points.
• Understanding the fidelity of the disease models should be improved by moving towards treating more advanced diseases, longer treatment window, and assessing efficacy via long-term outcomes such as portal hypertension, progression to cirrhosis and its sequelae.

2:00 pm Discovering the Effect of Anti-Claudin-1 Antibodies in Preclinical Models of Liver Fibrosis & Cancer

Synopsis

• Deep diving into translational models: ex vivo human (liver spheroids, liver slices), mice with humanized livers, predictive liver signature
• Investigating Claudin-1 as a therapeutic target in advanced liver disease

1:30 pm Discovering Resmetirom: A Selective Thyroid Hormone Receptor Beta Agonist in Phase 3 Clinical Development for the Treatment of NASH

  • Becky Taub Founder, Director, CEO & President, Madrigal Pharmaceuticals

Synopsis

• Resmetirom development: The MAESTRO Phase 3 trials, multinational, double-blind, randomized, placebo-controlled clinical trial of resmetirom in patients with NASH and liver fibrosis
• Outlining the challenges with NASH trials
• Hearing how to create a foolproof plan to successfully recruit patients for NASH clinical trials

2:00 pm Uncovering DUR-928, DNMTs, Alcohol-Associated Hepatitis & NASH

Synopsis

• Outlining how DUR-928 acts as an epigenetic Regulator that inhibits DNMTs
• Learning about hypermethylation and elevated DNMTs in Alcohol-Associated Hepatitis
• Revealing DUR-928 clinical results and outlining our ongoing program in Alcohol-Associated Hepatitis & NASH

2:30 pm Progressing towards a Sensitive and Reliable Endpoint for Treatment Efficacy

Synopsis

• New Data from Clinical Trials (response to new pharma therapy, reproducibility, progression to decomp in cirrhosis, portal hypertension)
• Pivotal Study and Regulatory Progress
• Anticipated Timelines for Clinical Trial and Commercial Scale-up

3:00 pm Exploring Aramchol – Lessons Learned & Optimization Towards Registrational Part of Phase 3 Clinical Study

Synopsis

• Explaining liver fibrosis – from basic pathophysiology to mechanism of action of drug candidates.
• Targeting liver fibrosis: Understanding its main challenges.
• Aramchol 101: Discovering its mechanism of action, compound optimization, and resulting clinical efficacy.

Comprehensively Analyzing the Latest Research on the Human Genetics of NASH

3:30 pm Reserved for Icon

4:00 pm Using Human Genetics to Identify Novel Targets for NAFLD/NASH: Opportunities & Challenges

Synopsis

• Hearing how human genetics have shown promise in identifying potential therapeutics for many diseases.
• Utilizing large human genetics resources for NAFLD/NASH and understanding how these have been challenging to collect and assemble.
• Exploring why surrogate phenotype data, such as liver fat or liver enzymes may also be good sources of data for target identification

4:30 pm Deep Phenotyping Human Livers to Discover & Validate Novel Targets

  • Quin Wills Cofounder and Chief Scientific Officer, Ochre Bio

Synopsis

• Spatially sequencing 1000 human livers to discover new targets
• Single-cell sequencing of cultured human liver slices to validate targets
• Temporal sequencing of whole perfused NAFLD human livers to test RNA therapies

5:00 pm Exploiting Human Genetics to Identify Therapeutic Targets for NAFLD

  • Stefano Romeo Professor in Molecular and Clinical Medicine, University of Gothenburg

Synopsis

• Exploring the relationship between NASH and human genetics
• Learning how to manipulate the relationship to strategically identify viable targets for NASH/NAFLD
• Investigating common challenges associated with utilizing genetics for target identification and learning to overcome them

5:30 pm End of Day One