Conference Day Two
8:00 am Morning Coffee & Check-In
8:55 am Chair’s Opening Remarks
Unlocking Clinical & Regulatory Success to Build Safer, More Effective TCE Strategies for Autoimmune Indications
9:00 am Leveraging Key Learnings From CLN-978’s Clinical Studies & Regulatory Success to Better Apply Your TCE in Autoimmune Trials
Synopsis
- Reviewing the clinical study design for the T-cell engager, CLN-978, to maximize the efficiency of your clinical development path – investigating where T-cell engagers are best fit in the treatment timeline for the specific modality
- Understanding the patient selection process and applying this a specific disease type: Do we start with healthy volunteers? Which patients benefit from which targets? What are the implications of different jurisdictions of running these trials?
- Investigating the regulatory landscape and hurdles for preclinical and clinical studies with T-cell engagers in autoimmunity, and understanding how CLN-978 were able to overcome this to create a successful dosing schedule with follow up safety
Exploring Protein Engineering Approaches of T-Cell Engagers Through Selective Activation to Improve Specificity, Potency & Safety
9:30 am Maximizing Therapeutic Impact with CD20- and CD19-Targeted T Cell Engagers in Autoimmune Disease
Synopsis
- Evaluating B cell expression in CD20 vs CD19 to weigh the risks and benefits
- Engineering Bispecific antibodies by selecting the most effective formats for autoimmune disease applications
- Tuning the potency and half-life of Bispecific antibodies to optimize their therapeutic index
10:00 am Engineering the Next Generation of T-Cell Engagers Through Selective Activation to Improve Specificity, Potency & Safety
Synopsis
- Advancing beyond first-generation TCEs by unpacking the rationale behind engineering trispecific molecules to selectively engage CD8+ T-cells and how this improves specificity and reduces off-target activity in autoimmune disease
- Designing conditional activation for enhanced safety: Explore how activity restricted to target-bound TCEs helps minimize unwanted immune activation and cytokine release, with implications for autoimmune disease therapy
- Comparative engineering strategy: Contrasting AstraZeneca’s novel TCE architecture against first-generation engagers and competitor approaches, highlighting how molecular design choices influence preclinical performance and translational potential
10:30 am Morning Break & Networking
Synopsis
The ideal opportunity to get face-to-face with many of the brightest minds in TCEs for Autoimmunity to engage with attendees for important in-depth conversations
Looking Beyond T-Cells or B-Cell Depletion to Overcome Exhaustion & Immunosuppression & Cytokine Release Syndrome
11:00 am Novel Biologics to Promote T-Cell-Mediated Depletion of Pathogenic Cell Types in Autoimmune Disease
Synopsis
- Immuno-STAT™ platform enables selective regulation of antigen-specific T-cells
- CUE-501 differentiates from pan-TCEs by selectively engaging existing virus-specific T-cells to deplete pathogenic B cells while minimizing systemic immune activation and CRS risk
- Modular nature of the Immuno-STAT™ platform enables opportunity to target additional pathogenic cell types beyond B cells, opening avenues for precise immunomodulation in autoimmunity
11:30 am Advancing B Cell Depletion Without T-Cells: Leveraging GEM-DIMER Technology to Mitigate Cytokine Toxicity in Autoimmunity
Synopsis
- Designing T-cell-independent bispecifics for autoimmune B cell depletion to avoid key TCE-associated liabilities
- Demonstrating potent B cell depletion and favourable safety in NHP in vivo
- Positioning for autoimmune indications where reduced cytokine release is essential for patient tolerability
12:00 pm Lunch Break & Networking
Investigating Preclinical Strategies for Autoimmune TCEs From Rare Immune Cells to Human Relevant Safety Models to Improve Regulatory Confidence
1:00 pm Activating the Potential of Gamma Delta T-Cells in Preclinical Models: A Next-Generation Strategy to Minimize CRS & Rethink TCE Safety in Autoimmunity
Synopsis
- Introduction to the potential of gamma delta T-cells and tackling the challenge of their limited presence in patients by engineering engagers that expand and activate these cells in vivo without relying on CD3 stimulation
- Exploring ways to safely increase levels of rare immune cells like gamma delta T-cells and NK cells inside the body for effective targeting
- Discuss limitations of oncology-based animal models for autoimmune settings and examine strategies with gamma delta T-cells to validate lymphoid tissue targeting, depletion efficacy, and safety in the absence of conventional cytokine-driven biomarkers
1:30 pm Development of a CD3 VHH Platform that Enables the Rapid Testing of Multiple T-Cell Engager Configurations for Optimal Use Cases
Synopsis
- Discussing the development of identifying and engineering a cyno-cross reactive CD3 VHH platform with properties suitable for either oncology or immunology
- Demonstrating the ease of evaluating multiple CD20 TCE configurations with the CD3 VHH binding arm to determine an optimal lead
- Brief overview on how a CD3 VHH simplifies the development of the next generation of T cell engagers
1:40 pm Preclinical Comparison of Two CD3xB7H4 bsAbs with Divergent CD3 Affinities for the Treatment of Solid Tumors
Synopsis
- Discussing the impact of CD3 affinity on the trade-off between efficacy and safety in preclinical solid tumor models
- Exploring how translational insights around antigen expression levels, bystander activity, and tolerability in tumor models may carry over to chronic inflammatory indications
- Reflection on how learnings from immuno-oncology TCE design may inform safer and more effective strategies in autoimmune disease settings
2:10 pm Afternoon Break
2:40 pm Panel Discussion: Investigating Preclinical Platforms for Autoimmune T-Cell Engagers From Human Relevant Assays to Regulatory Confidence
Synopsis
- For TCEs in autoimmunity, conventional preclinical tools, often adapted from oncology, fall short in capturing the inflammatory, chronic, and tissue-specific nature of disease.
- This panel will explore how to build assays that reflect real autoimmune biology, capture safety-relevant signals, and avoid reliance on transgenic animals. With human target expression and immune context being essential, developers are rethinking how they model tissue penetration, subset-specific depletion, and chronic inflammatory responses e.g. for emerging modalities like gamma delta T-Cell engagers.
- Regulatory expectations are also evolving, and this session will address what evidence best supports safe and effective IND filings.
- Building disease-relevant in vitro systems that incorporate inflammatory cytokine environments to reflect autoimmune activation states
- Demonstrating selective target cell depletion and tissue or lymph node engagement in the absence of exaggerated cytokine release or off-target killing
- Replicating chronic, low-grade inflammatory contexts in preclinical assays to detect tolerability and null responses rather than acute cytotoxic triggers
- Evaluating the translational relevance of preclinical models, such as for gamma delta T-cell engagers and define how to justify safety and efficacy without conventional animal studies