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

  • Milton To Senior Scientist, Vir Biotechnology Inc.

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?

  • Kris Sachsenmeier Vice President, Head of Translational Science, Compass Therapeutics

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

  • Alex Martinko Director, Antibody Engineering & Design, Cartography Biosciences, Inc

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

  • Saso Cemerski Executive Director & Head of Immune Engagers, AstraZeneca

2:45 pm Afternoon Break & Networking

3:15 pm Using Trispecific T-Cell Engagers Alongside Checkpoint Inhibition to Enhance the Therapeutic Applications of TCEs

  • Nina Weisser Director - Multispecific Antibody Therapeutics, Zymeworks

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

  • Simon Plyte Chief Scientific Officer, BIOMUNEX Pharmaceuticals

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

4:15 pm Chair’s Closing Remarks

4:20 pm End of Scientific Program Day Two