Scientific Program Day Two | Wednesday, June 25
8:00 am Check In & Coffee
8:50 am Chair’s Opening Remarks
Unmasking Safety: Using Conditionality to Cloak Cell Engagers & Reduce On-Target Off- Tumor Toxicity
9:00 am Developing Precision-Activated T-Cell Engagers to Improve Specificity in Solid Tumors
Synopsis
- Enhancing safety by incorporating stearic masks into T cell engagers, minimizing systemic toxicity
- Leveraging protease-cleavable linkers that unmask and activate T cell engagers in the presence of tumor-specific proteases, enhancing targeted immune activation in solid tumors
- Optimizing tumor-specific activation to expand therapeutic index and minimize on-target, off-tumor effects of potent T cell engagers
Moving from Dirty to Clean Targets: Identification of Distinct Markers for Target Selection in Next-Gen TCEs
9:30 am Roundtable Discussion: CD19, CD20, BCMA – What is the Optimal Target for Autoimmune Indications?
Synopsis
- Comparing the therapeutic potential of CD19, CD20, and BCMA as targets for autoimmune diseases, considering immune cell populations and disease pathophysiology
- Evaluating safety and efficacy profiles of targeting these antigens, including off-target effects, potential for immune depletion, and long-term durability
- Exploring optimal strategies for T-cell engager development, including antigen selection, dosing regimens, and combination therapies to achieve targeted immune modulation
10:15 am ERAP1 Inhibition Reveals Novel MHC-Peptides for Targeting – Discovery, Pre- & Clinical Development Opportunities
Synopsis
- We are global leaders in the therapeutic development of ERAP1 inhibitors, with clinical trials progressing in oncology
- ERAP1i changes the immunopeptidome on classical (HLA-A*, HLA-B*) and non classical (HLA-E, HLA-G) molecules to affect CD8 T cell and NK cell responses
- Pre-clinically, ERAP1i enables detection and quantification of novel tumor associated and viral peptides informing the development of peptide-MHC targeted therapeutics
- These datasets highlight novel development opportunities in oncology, virology and autoimmunity
10:45 am Morning Break & Networking
11:15 am Reviewing the Benefits of Using TCR Based Cell Engager Rather than an Antibody Based Cell Engager to Bind to MHC Over Epitopes
Synopsis
- Assessing the advantages of TCR-based cell engagers in recognizing MHC-bound epitopes over antibody-based approaches, with improved specificity for tumorassociated antigens
- Enhancing T-cell activation by utilizing TCRs that recognize native, processed epitopes, minimizing reliance on antibody interactions and enhancing immune response precision
- Optimizing TCR-based engagers for solid tumor targeting, considering TCR affinity, tumor antigen presentation, and potential for reduced immune escape mechanisms
11:45 am Pioneering Next Generation HLA Directed Engagers to Achieve High Precision, Tumor Agnostic Targeting of Solid Tumors
Synopsis
- Exploiting tumor exclusive mutations as therapeutic targets to deliver off the shelf, precision T cell engagers
- Leveraging tumor specificity to enhance T cell activation and expand the therapeutic window in solid tumors·
- Catalyzing anti-tumor activity and counteracting immune resistance with novel HLA redirecting engager combination approaches
12:15 pm Lunch & Networking
1:15 pm Single Cell RNA Sequencing Technologies Approaches to Identifying Novel Targets for T-Cell Engagers
Synopsis
- Applying single-cell RNA sequencing technologies to identify novel tumor-associated antigens and immune cell markers for targeted T-cell engager development
- Integrating single-cell transcriptomic data to uncover tumor heterogeneity, immune escape mechanisms, and potential targets for precision T-cell engagement
- Optimizing target selection by leveraging single-cell sequencing insights to identify differential gene expression patterns and immune cell populations critical for T-cell engager efficacy
Beyond Traditional T Cells: Investigating Multispecifics, Gamma Delta Cell Engagers & Beyond for Higher Tumor Specificity & TCE Selectivity
1:45 pm A Machine Learning-Driven Approach to Overcome On-Target, Off-Tumour Toxicity in Multispecific Antibodies Using Avidity-Driven Selectivity
Synopsis
- Combining high-throughput experimentation with ML to co-optimise multispecifics for function and developability
- Discovering HER2xCD3 TCEs with killing selectivity corresponding to >400-fold improvement versus clinical benchmarks
- Developing a pipeline of highly selective VHH-based TCEs against targets with TAA expression differences of 3-fold between health and diseased cell lines
2:15 pm Session Details to be Confirmed
2:45 pm Afternoon Break & Networking
3:15 pm Using Trispecific T-Cell Engagers Alongside Checkpoint Inhibition to Enhance the Therapeutic Applications of TCEs
Synopsis
- Combining trispecific T-cell engagers with checkpoint inhibition to simultaneously target tumor cells, activate T-cells, and block immune suppressive pathways, enhancing antitumor immunity
- Optimizing trispecific T-cell engager design to improve tumor specificity, T-cell recruitment, and immune checkpoint blockade for synergistic therapeutic effects
- Exploring the clinical potential of trispecific engagers with checkpoint inhibitors in solid and hematologic tumors to improve response rates and reduce immune evasion
3:45 pm MAIT Engagers: Potent & Safer Immune Cell Engagers to Treat Solid Tumors
Synopsis
- Improving the safety profile of T-cell engagers by selectively targeting MAIT cells
- MAIT engagers do not activate regulatory T-cells and restrict cytokine release
- Leveraging human ex vivo data (tumour / organoids) to demonstrate the potential to
- treat cancer