Conference Day Two
Thursday, September 26, 2024
7:30 am Check-In
8:25 am Chair’s Opening Remarks
8:30 am Utilizing RWD/RWE to Improve Drug Development Efficiency
Synopsis
- Detailing the RWD/RWE regulatory landscape including FDA, EMA, PMDA and CDE
- Navigating global regulatory harmonization and convergence
- Utilizing case studies to predict future trends
9:00 am Streamlined and Standardised Endpoints: Adopting Quantitative Imaging and Digital Pathology in MASH and Obesity Trials
Synopsis
- Understanding treatment response in MASH and its metabolic co-morbidities using quantitative multi-organ imaging and MRI body composition
- Streamlining key primary and secondary endpoints in MASH and cirrhosis clinical trials through digital pathology and endoscopy central reads
9:30 am Proteomic Approaches to Identify Disease and Treatment-Response Biomarkers
Synopsis
- Predictive value and utility of Somascan MASH assay
- Identification of circulating biomarkers associating with steatosis and inflammation
- Clinical insights into mechanisms of Acetyl CoA Carboxylase (ACC) inhibition in MASH
10:00 am Serological fibroblast & ECM biomarkers of Prognosis, Diagnosis, Efficacy of intervention & Prediction
Synopsis
- Fibroblast activation is highly prognostic for liver, kidney and heart outcomes
- Weight dependent and weight independent de-activation of fibroblasts
- Tissue formation and tissue degradation: Matching Patient endotypes to treatments
10:30 am Morning Break & Networking
Track 1: Preclinical & Translational
Exploring Innovative Therapies for Liver Fibrosis: siRNA Approaches & Portal Fibroblast Ablation
11:15 am Elucidating the Potential of siRNA Approaches for MASH: The Promise of MITO1041
Synopsis
- siRNA therapies can modulate targets that were previously considered un-druggable by conventional small molecule or large molecule approaches
- A GalNAc-SiRNA therapeutic approach is a novel modality to specifically target a single gene in the liver without impact on non-hepatic tissues, leading to a good safety profile
11:45 am Delving into Portal Fibroblast Ablation to Treat Cholestatic Fibrosis
Synopsis
- Activated Portal Fibroblasts (aPFs) and Hepatic Stellate Cells (aHSCs) contribute to populations of myofibroblasts in response to cholestatic liver fibrosis. Ablation of myofibroblasts with cellspecific immunotoxins or CART cells has been suggested as a potential immunotherapy of liver fibrosis
- Ablation of aPFs suppresses cholestatic liver fibrosis without causing mortality or distress in mice and can be used for treatment of cholestatic liver fibrosis
- Ablation of HSCs suppresses liver fibrosis but affects hepatocyte proliferation causing a defect in liver regeneration. Total ablation of HSC population cannot be used for anti-fibrotic therapy
Track 2: Clinical & Regulatory
Utilizing Machine Learning & PPARs to Accelerate MASH Development
11:15 am Leveraging Quantitative Tools to Integrate Preclinical and Clinical Data to Advance MASH Drug Development
Synopsis
- Integrating preclinical and clinical data via mathematical modeling predicts pharmcoldynamic effects on MASH biomarkers
- Mathematical models also characterize the relationship between MASH biomarkers and histological endpoints
- AI/ML techniques aiding participant selection and test model predictions to reduce screen failures
11:15 am The Potential of Pan-PPAR Agonist Therapy to Address Inflammation and Fibrosis in Patients with MASH – a Path to a Holistic Approach
Synopsis
- Delving into the anti-fibrotic and anti-inflammatory impacts
- Assessing developments from Phase 3 trials
12:15 pm
Lunch
Integrating Current & Combination Therapies into Clinical Practice and Addressing Real-World Challenges
1:15 pm Exploring the Need for Regulatory Guidance for Decompensated MASH
Synopsis
- Analysing the need for guidelines for this critical population
- Considering necessary updates to account for differences in endpoints
- Guidance on patient selection and risk stratification
1:45 pm Further Rationales for Holistic Approaches to Treating MASH & Metabolic Diseases
Synopsis
- Brief overview of epidemiology and risk factors in MASH and metabolic diseases including the added risks when multiple metabolic diseases are present
- Discuss the preliminary benefits observed in metabolic and hepatic endpoints in Phase 2 studies of berberine ursodeoxycholate
2:15 pm Spotlighting Clinical Data Supporting Anti-Fibrotic Mechanisms of EFX
Synopsis
- Detailing direct and indirect antifibrotic activity of EFX shown clinically
- Improving insulin sensitivity and restoring lipoprotein profile to restore metabolic health and achieve sustained responses
- Dissecting the implications of these findings on long term clinical outcomes
2:45 pm
Afternoon Break
Showcasing Antifibrotic Progress, Past Learnings & Innovations to Supercharge MASH Drug Development
3:15 pm Harmonizing Patient Engagement & Patient-Centered Clinical Trials
Synopsis
- Evaluating efforts to drive patient focused drug development
- Promoting diversity in MASH trials to increase access and representation
- Utilizing case studies from MASH POWER Council
3:45 pm Detailing the Best Practices for Patient Engagement
Synopsis
- Exploring the impact of recent approval on the patient journey
- Exemplifying best code of practise
- Implementing strategies to enhance patient-focused drug development
4:15 pm Demonstrating Denifanstat’s Differentiated Approach in MASH with Mechanistic & Clinical Data Showing Direct Anti-Fibrotic Activity
Synopsis
- Use of primary stellate cells to show that denifanstat directly blocks fibrotic activity
- Demonstrating significant histological efficacy in FASCINATE-2 on endpoints of NASH resolution and fibrosis improvement
- Clinical use of biopsies and biomarkers to manifest effects of FASN inhibition against the 3 hallmarks of MASH; liver fat, inflammation, and fibrosis