Agenda

Fibrosis begins through different organ-specific injuries, but many pathways may 

converge around fibroblast activation, immune-stromal crosstalk, mechanotransduction, 

ECM remodeling, and failed repair. This workshop will compare fibrogenic cascades 

across lung, liver, kidney, gut, and skin to determine where fibrosis becomes targetable, 

when intervention is most likely to succeed, and whether mechanisms support panfibrotic or indication-specific strategies.

Discussion Topics Include:

• Mapping common downstream fibrotic pathways involving fibroblast activation, ECM deposition, and mechanotransduction across organs
• Understanding organ-specific inciting injuries, epithelial responses, and immune microenvironments that drive early disease
• How spatial omics, niche-specific activation cues, and cross-organ learnings are enabling more precise, safer antifibrotic strategies
• Determining at which disease stage cross-indication therapeutic approaches become most viable versus requiring tissue-specific targeting

Developing effective antifibrotic therapies demands translational strategies that extend 

and meaningfully complement conventional animal models. This workshop will focus 

on defining the translational path forward for FIB992, an oral DDR1 inhibitor, by 

integrating human-relevant preclinical models, patient-derived systems, translational 

biomarkers, and clinical insights from kidney transplantation. The discussion will 

highlight how these complementary approaches can strengthen target validation, 

support patient selection, establish proof of mechanism, and de-risk clinical 

development toward preserving long-term kidney allograft function.

Key Talking Points:

• Leveraging a patient-centric forward- and back-translation strategy to generate mechanistic insights and build a translational evidence package for FIB992 toward clinical proof-of-concept 
• Establishing the biological rationale for DDR1 inhibition by integrating genetic KO models, human kidney allograft biopsy biobanks, and transcriptomic datasets to demonstrate that DDR1 expression and activation are associated with molecular fibrosis signatures, disease progression, and long-term graft dysfunction
• Leveraging human ex-vivo translational platforms, including precision-cut kidney slices (PCKS) and patient-derived kidney biopsies, to demonstrate FIB992-mediated reversal of profibrotic molecular programs, extracellular matrix remodeling, and immune–fibrotic interactions
• Establishing a translational pharmacodynamic strategy by developing robust target engagement assays to quantify DDR1 inhibition in preclinical studies, healthy volunteers, and kidney transplant recipients, and linking target engagement to modulation of downstream fibrotic pathways and molecular signatures

As antifibrotic developers aim to intervene earlier in disease, traditional endpoints such 

as FVC, eGFR, biopsy, and long-term clinical outcomes may be too slow, invasive, or 

insensitive to demonstrate early therapeutic benefit. This workshop will explore how 

biomarker, imaging, and endpoint strategies can be integrated to detect antifibrotic 

efficacy sooner, enrich the right patients, and build confidence in early proof of disease 

modification.

Discussion Topics Include:

• Integrating multi-omic approaches combining proteomics, spatial transcriptomics, and single-cell sequencing to capture the complexity of fibrotic disease progression, improving trial success rates and accelerating paths to approval
• Defining what earlier proof of antifibrotic efficacy should look like across lung, kidney, liver, gut, and skin fibrosis, and where traditional endpoints such as FVC, eGFR, biopsy, and long-term outcomes fall short 
• Evaluating how circulating biomarkers, imaging, digital pathology, collagen turnover markers, and molecular signatures can be integrated to detect treatment response earlier 
• Utilizing non-invasive biomarker strategies including blood-based assays and advanced imaging to enable frequent longitudinal monitoring, improving patient recruitment and retention while detecting drug activity with greater sensitivity
• Navigating regulatory hurdles in endpoint acceptance