7:30 am
Networking Breakfast
8:25 am Chair’s Opening Remarks
From Bench to Bedside: Exploring Regenerative Medicine to Restore Liver Health & Optimize Clinical Treatment
8:30 am Fact or Fiction? Unraveling Regenerative Medicine for the Treatment of Liver Damage
Synopsis
- From treating symptoms to curing disease: what is the next milestone in liver injury?
- Exploring the potential for precision medicine approach to regenerative treatment
- Future opportunities: advancing the frontier of regenerative medicine in endstage liver disease
9:00 am Human Liver Precision Cut Slices (PCLS): The Unrivalled Preclinical Platform for Development & Testing of Anti-Fibrotic Therapeutics
Synopsis
- Describing the development of human Precision Cut Liver Slice (PCLS) methodologies
- Providing examples of how these platforms are utilized for commercial drug development
- Discussing the use of human PCLS as preclinical drug testing platforms using real life examples
9:30 am Interrogating Cell Therapy Approaches to Liver Regeneration
Synopsis
- Exploring the potential of replacing diseased liver tissue to restore liver health
- Advancing cell therapies to replace liver transplants and actively repair damaged tissues
- Developing cell lines suitable for tissue regeneration in the liver
10:00 am
Morning Break & Networking
Leveraging Robust Preclinical Models to Predict Target Engagement
11:00 am Results from the LITMUS Preclinical Retrospective Study: A Novel Unbiased Approach to Rank Murine NASH Models Based on Proximity to Human Disease
Synopsis
- Review how a wide-ranging retrospective review of 42 commonly used murine models was conducted
- Learn how a novel algorithm was developed to evaluate preclinical models to human NASH in 3 categories: phenotype, histology, and liver transcriptome
- Discover how separate rankings are provided for models based on relevance to NAFLD development and NASH fibrosis
11:30 am The “Free Choice” Diet-Induced Obese Hamster for Evaluating Drugs Targeting NASH & Fibrosis: A Promising Alternative to Mouse & Rat Models
Synopsis
- Emphasizing the limitations of diet-induced mouse and rat models for evaluation of drugs targeting NASH/liver fibrosis
- Describing the free choice diet-induced obese hamster as a preclinical model for NASH, liver fibrosis and associated heart failure with preserved ejection fraction
- Presenting the effects of clinical benchmarks demonstrating the relevance of the hamster model for drug efficacy studies
11:45 am Panel Discussion: Liver Organoids, Precision-Cut Liver Slices & Animal Models: Interrogating Diverse Preclinical Models to Understand Pathophysiology & Screen Targets
Synopsis
- Which are the best preclinical models? Recapitulating complex architecture and metabolic function in liver tissue to test therapeutic efficacy
- Investigating emerging platforms and technologies for disease modeling and regenerative therapy
- From research to therapeutics application: bringing the translational gap
Innovating Clinical Trial Design to Engage Patients & Optimize Study Outcome
11:00 am Evolving Innovative Trial Design with Diverse Patient Populations to Optimize Clinical Development
Synopsis
- Designing a robust development program to accelerate drug development
- F1, F2, F3, F4: navigating diverse patient populations in clinical studies to optimize treatment
- Evaluating clinical development of EFX in Phase IIb and histological outcomes
11:30 am Leveraging a Non-Invasive Strategy for More Effective NASH Trials: From Patient Selection to Predicting Outcomes
Synopsis
- Enrichment of patient population with a complementary biomarker strategy
- Utility of an MR-based approach for monitoring
- Uncovering the association between NASH biomarkers and Clinical Outcomes
11:45 am How Sustainable is Drug-Based Management of Chronic Obesity & When Should Treatment Start?
Synopsis
- Finite treatment beyond GLP-1 receptor agonists: establishing sustainable treatment of obesity
- Advancing a safer and more potent method to address the medical need of obese patients in combination with other treatments
- Navigating early intervention: when does it make sense to start treating patients?
12:15 pm
Lunch & Networking
Cardiovascular, Metabolic & Kidney Diseases: Organ System Crosstalk in the Age of Multimorbidity
1:00 pm One Drug Multiple Targets: Simultaneously Modulating Several Target Genes in Obesity, Diabetes & MAFLD
Synopsis
- Developing targeting microRNA oligonucleotide therapeutics for cardiometabolic disorders
- Mice, rats, monkeys, and in silico: demonstrating proof of efficacy in vitro in primary cultures of human cells and animal models
- Modulating multiple target genes with miRNA ONTs to treat multi-factorial diseases
1:30 pm Hepatocyte Transplantation into the Upper Abdominal Lymph Nodes Through a Minimally Invasive Endoscopy Approach: Developing Ectopic Livers Through Organogenesis
2:00 pm Cholestatic & Metabolic Liver Disease: Uncovering A Mechanistic Understanding of FXR Agonist Induced Pruritus & its Therapeutic Potential
Synopsis
- Defining mechanistic understanding of FXR agonist induced pruritus and cholestatic pruritus
- Uncovering a key pruritogenic cytokine, IL31, as a candidate target of FXR agonism
- Investigating translation to the clinic: correlating IL31 with degree and severity of itch
Scaling the Chasm of Diagnosis & Patient Enrolment to Improve Meaningful Recruitment & Retention
1:00 pm Patient Segmentation & Enhancing Understanding of Efficacy: Leveraging Machine Learning to Predict Fast Progressors & the Value of MRI
Synopsis
- Constructing a model to predict survival time of patients with NASH and/or portal hypertension, and identify fast progressors
- Evaluating current performance in treating patients with cirrhosis and features of portal hypertension, real-world evidence
- Non-invasive biomarkers for portal hypertension: HVPG vs integrating MRI into clinical trials to monitor therapeutic efficacy
1:30 pm Using Real-World Data to Increase Study Efficiency: From Diagnosis to Enrollment to Recruitment to Retention
Synopsis
- Diagnosis: Identifying undiagnosed patients to expand potential enrollment pool
- Enrollment: Set realistic enrollment goals by estimating size of eligible patient pool through assessment of the prevalence of specific variables used to determine inclusion and exclusion
- Recruitment: Identifying patients at higher risk for developing outcome of interest using AI/ML
- Retention: Continuing to “follow” participants even if they no longer are actively participating in the study
2:00 pm Driving Innovation in Patient Selection: Rethinking Inclusion & Exclusion Criteria
Synopsis
- Investigating clinical trials for NASH in HIV-infected patients
- Evaluating novel biomarker outcomes in NASH and considering comorbidities
- Beyond NASH: driving studies in cardiovascular and metabolic disorders
2:30 pm
Afternoon Break & Networking
Dissecting Clinical Updates to Influence the Next Generation of Trials
3:00 pm Phase 3 Development of Resmetirom: A Selective Thyroid Receptor- Beta Agonist for the Treatment of NASH
Synopsis
- Examining the mechanism of action of thyroid receptor beta in the NASH liver
- Exploring Phase 3 development program for non-cirrhotic NASH
- Exploring Phase 3 development program for NASH – cirrhosis
3:30 pm Solutions to Improving Randomization Rates & Lower Screen Fail Rate
Synopsis
- Pre-screening patient journey with trial qualifying efficiency
- Departmental collaboration, aligning medical and business team
- Site study specific enrolling data analytics to improve business intelligence
4:00 pm Breaking New Ground in Targeting Dysfunctional Metabolic Pathways in the Liver: Inhibition of FASN in NASH Patients with the First-in-Class Drug, Denifanstat
Synopsis
- Evaluating the ability of FASN inhibition to improve the key drivers of NASH by: reducing liver fat, inflammation, and fibrosis
- Validating digital imaging and non-invasive diagnostics as biomarkers of liver injury and predictors of response in clinical trials
- Exploring initial clinical data in FASCINATE-2, a Phase IIb denifanstat study