Day Two

• Implementing standardized methodologies to create consistent and reliable potency assays for tolerance therapies, ensuring product quality and regulatory compliance
• Establishing clear acceptance criteria and validation protocols for potency assays, moving beyond theoretical frameworks to provide actionable guidelines for clinical and commercial applications
• Utilizing mechanistic insights from potency assays to predict therapeutic outcomes, guiding dose optimization and patient stratification for improved clinical efficacy

• Comparison of regulatory T cells, peripheral regulatory T cells, and alternative immunetolerance mechanisms, highlighting their distinct biology and therapeutic relevance
• Reviewing current preclinical and emerging clinical evidence, outlining how each approach contributes to immune modulation
• Insights into key challenges, translational hurdles, and notable successes that are shaping the future development of targeted immunotherapies 

• Creating models to mirror human disease biology to create predictive mechanically relevant models for autoimmune conditions
• Exploring the growing interest in in vitro and biomarker-based models that could complement or replace animal studies
• How significant are immune phenotypes in mice or other animals, how important are these immune changes and will they derive long lasting immune tolerance

• Explores T-cell subsets beyond B-cell depletion—particularly tissue-resident memory, follicular helper, and peripheral helper T cells—as key drivers of autoimmune persistence and B-cell activation
• Examines evidence that selective depletion or modulation of these T-cell and myeloid populations may deliver deep, durable disease control comparable to B-cell–targeted approaches
• Addresses translational challenges including efficient tissue-level depletion, optimizing delivery and biodistribution of therapeutic modalities, and defining biomarkers that capture local immune modulation

• Ahead MiMiTOPs display a broad, cross-disease mechanism of action
• Antigen-presenting cells from patients with T1D, RA, MG, MS and iTTP acquire a tolerogenic phenotype following interaction with MiMiTOPs. Dendritic cells and macrophages become tolerogenic, reducing their ability to drive autoreactive T cell proliferation, while B lymphocytes directly internalize MiMiTOPs and secrete TGF-β and IL-10, adopting an immunoregulatory phenotype
• Through coordinated effects on innate and adaptive immunity, MiMiTOPs provide an antigen-specific strategy to support long-term immune tolerance

NEW DATA

• Introduction to TargetScan, a cell-based, unbiased platform that pairs naturally presented antigens with their cognate TCRs
• Demonstrating TargetScan’s ability to identify both CD8⁺ and CD4⁺ T cell targets in example indications such as ankylosing spondylitis, birdshot uveitis, scleroderma, and ulcerative colitis
• Exploring novel biologically validated targets that enable antigen-specific tolerizing therapies in indications such as ankylosing spondylitis

• Applying AI to predict the most suitable antigens for immune tolerance, potentially accelerating discovery and improving target selection
• Many AI platforms exist, but validation of predicted antigens is still limited, and false leads remain a challenge
• Explore novel approaches, integrate new technologies, and refine predictive models for translational applications

• Highlighting a platform-centric gene editing strategy that harmonizes clinical protocols and manufacturing processes, allowing a single target modification to be applied across multiple autoimmune indications
• Showcasing a multi-indication clinical development pathway that leverages Phase I safety and mechanistic insights to accelerate Phase II expansion, streamlining translation across diverse disease contexts

NEW DATA

• Exploring the thymus – the central organ responsible for establishing and maintaining immune tolerance
• Development of iPSC – derived thymic cells that demonstrate in vivo T cell education to re-establish central tolerance in immune-related diseases
• Unlocking the potential of thymus – based regenerative medicine to restore immune balance