Day Two

• Exploring why and how chronic disease drug development should look beyond what goes wrong in disease and instead leverage the protective biology that enables younger, healthier tissues to cope with disease-associated stressors
• Demonstrating how FOXO3 activation modulates fibroblast and epithelial-cell transdifferentiation across fibrotic environments, providing a broader approach than targeting a single disease-driving pathway
• Building an integrated evidence package by utilizing a variety of models, including tissue slice models, to demonstrate the potential of Refoxy’s lead program

• Identifying shared regenerative pathways that can be therapeutically leveraged across pulmonary, cardiac, hepatic, dermatological, and other fibrotic diseases
• Translating multi-omic insights from nature’s super-regenerators into druggable mechanisms that restore regenerative capacity following chronic tissue injury
• Applying generative AI to design novel peptide therapeutics that modulate pathological remodeling and promote the recovery of healthy tissue architecture and function

• Reflecting on the discoveries that have enabled antifibrotic therapies to slow disease progression, and debating whether these same insights are sufficient to guide therapies that stop or reverse fibrosis
• Defining what true fibrosis regression means, including ECM remodeling, fibrinolysis, fibroblast deactivation, restored tissue architecture and functional recovery
• Determining whether different cell types, molecular mechanisms, datasets, biomarkers, and clinical trial designs are needed to distinguish therapies that slow progression from those that actively reverse fibrotic disease

• Defining hot & cold fibrosis endotypes using histological features, immune cell infiltration, & molecular signatures
• Developing non-invasive biomarker panels to identify patients in inflammatory versus quiescent fibrotic phases without requiring biopsy
• Tailoring therapeutic approaches & trial inclusion criteria based on disease endotype to maximize treatment effect size

Practical and highly interactive breakout roundtables where attendees can crowd 

source solutions and share opinions around pre-assigned topic areas.

• Integrating multi-omics, spatial biology, and digital pathology to identify predictive biomarkers, pathogenic fibroblast subpopulations and novel therapeutic targets
• Aligning therapeutic mechanism, patient selection strategy and biomarker development from early discovery through clinical translation
• Determining how biomarkers can support target identification, responder stratification, treatment monitoring and endpoint development across the antifibrotic pipeline
• Discussing how early integration of translational biomarkers can reduce clinical uncertainty, accelerate proof-of-concept and improve confidence in disease-modifying potential

Moderator Feedback & Audience Debate 

Moderators will be assigned to each roundtable to facilitate discussion and collate 

the findings. Following the roundtable discussions, they will present back to the entire 

delegation and open wider audience debate

• Examining what the resmetirom clinical programme and post-approval experience have revealed about fibrosis regression, MASH resolution, and the characteristics of patients most likely to benefit
• Translating insights from serial biopsy, non-invasive testing, and longitudinal treatment response back into research to refine target validation, biomarker strategies, and preclinical models
• Understanding which elements of the development pathway could be applied across other fibrotic indications
• Exploring how emerging clinical and real-world data can guide lifecycle development, combination strategies, and the identification of additional patient populations where the underlying biology may be relevant

• Building pathobiology maps from large human transcriptomic, proteomic, and clinical biomarker datasets to identify disease-associated biological modules
• Mapping human pathobiology onto in vitro and in vivo data to identify relevant translational models
• Integrating interventional pathway-specific biomarker data into a self-reinforcing framework for driving programs toward the clinic

• Anti-fibrotic tolerability failures are largely predictable from mechanism rather than molecule: kinase inhibition, cAMP elevation and TGFβ blockade each collide with a physiological process the healthy adult still needs
• TRX-44, a first-in-class albumin-fused CCN5 mimic, inhibits signalling from the disease-selective, pro-fibrotic CCN family without target-mediated drug disposition, supported by clean 4-week GLP toxicology in rat and cynomolgus monkey
• Concentration-dependent CCN ligand displacement and osteopontin reduction in IPF patient-derived bronchospheres and precision-cut lung slices underpin the PD biomarker strategy for clinical transition

• Disrupting ECM-driven myofibroblast adhesion to promote selective myofibroblast apoptosis
• Understanding how diseased ECM influences early fibrotic signalling & creates new therapeutic intervention points
• Demonstrating activity across preclinical lung & kidney fibrosis models while assessing organ-specific ECM biology
• Applying artificial intelligence (AI)-guided indication selection to identify where an early ECM-focused programme could deliver the greatest impact