Conference Day One
Wednesday, April 2
7:30 am Check-In & Coffee Networking
8:25 am Chair’s Opening Remarks
Validating the Safety & Efficacy of TCR-Based Therapies in the Clinic
8:30 am ACTengine IMA203 & IMA203CD8 TCR-T Cell Therapy Targeting PRAME in Solid Tumor Patients
Synopsis
• Phase 1b clinical data on IMA203 demonstrate deep and durable responses in heavily pretreated metastatic melanoma patients at RP2D
• Next-generation IMA203CD8 Phase 1a dose escalation data show enhanced pharmacology and potency per cell; to be evaluated for future in development in solid cancers with medium-level PRAME copy numbers
• SUPRAME, randomized-controlled Phase 3 trial to evaluate IMA203 in 2L+ metastatic melanoma patients, initiated in December 2024
9:00 am T-Cell Therapies in the Real World
Synopsis
- Data supporting FDA approval of afamitresgene autoleucel, the first engineered T-cell therapy for solid tumors, targeting unresectable or metastatic synovial sarcoma
- Optimizing the regulatory process throughout development, and paving the way for future cell therapies
- Data from the IGNYTE ESO trial with letetresgene autoleucel for the treatment of synovial sarcoma and myxoid/round cell liposarcoma (MRCLS)
9:30 am Next Generation TIL: OBX-115 Engineered TIL Cell Therapy with Regulatable mbIL15
Synopsis
• OBX-115 is an engineered TIL cell therapy that leverages regulatable membrane-bound IL15 (mbIL15) to improve the expansion, persistence, safety, and efficacy of TIL cell therapy for patients with solid tumors
• Unlike IL2, mbIL15 promotes a predominant CD8+, memory, and “stem-like” progenitor phenotype, and does not increase immunosuppressive regulatory T-cells
• Clinically, we have observed a safety profile that is positively differentiated from nonengineered TIL cell therapy, which requires high-dose systemic IL2, as well as promising early efficacy and translational correlates
10:00 am Panel Discussion: Evaluating the Cell vs Bispecific Evolution to Elevate Their Respective Advantages
Synopsis
• Consolidating the clinical advances for both approaches while highlighting the next generation for each method
• Comparing clinical efficacy and safety data to highlight benefits and challenges of each modality
• Discussing how the impact of various targets and TCR enhancements may differ for each approach to determine priorities for future modification
• Reflecting on where each modality thrives and how they can learn from each other to further advance the TCR-based
therapy field
10:45 am Morning Refreshment Break & Speed Networking
Approaching Effective TCR Discovery & Optimization to Mediate Safe & Effective Targeting
11:35 am Showcasing a Cellular TCR Evolution Platform to Upcycle TCRs for Clinical Deployment
Synopsis
• A novel platform to generate clinically actionable TCRs beyond the native TCR repertoire
• Utilizing synthetic biology to diversify TCR frameworks and functionally select variants in T-cell libraries
• Validating optimized TCR for allo-reactivity and cross-reactivity to demonstrate safety
12:05 pm Developing a Robust, Antigen-Agnostic In Silico Prediction Model to Select & Test Personalized TCRs (pTCRs) for Tumor-Reactivity
Synopsis
- Predicting tumor-reactive pTCRs via gene signature to enable target diversity and rapid TCR discovery
- Generating wet-lab TCR validation data in a high-throughput format to train prediction model
- Validating selected pTCRs using patient-derived tumor organoids to inform preclinical efficacy
12:35 pm Breaking Down Solid Tumor Barriers with a Novel Bispecific T-Cell Engager Against a Novel pHLA Target
Synopsis
• Leveraging the 3T-TRACE platform to screen TCR and TCR mimetic molecules for specific and off-target cross-reactivities
• Building highly specific and safe TCRs for shared targets to effectively treat solid tumors
1:05 pm Self-Validating Tools for Functional Pan-HLA Epitope & TCR Discovery
Synopsis
- Data from our lab demonstrating the need for wet-lab validation/discovery methodologies that do not rely on predictive tools or unproven input
- T-FINDER (T-cell functional identification and (Neo-)antigen discovery of epitopes and receptors) is a modular, plug and-play system for high-throughput interrogation of putative TCR:ligand interactions for both class I and class II HLA presented epitopes
- ESTEL (Epitope-specific T-cell expansion on libraries) is an HLA-agnostic tool for identifying TCRs of interest on a set of putative ligands
1:15 pm Lunch Break and Networking
Synopsis
Private Lunch with Miltenyi
Reflecting on the Year & Turbocharging Future Success of the TCR Field
2:15 pm Industry Leaders’ Fireside Chat: A Commercial TCR-T & TCR Bispecific – What’s Next?
Synopsis
• Reflecting on the past: celebrating the first TCR-T commercial approval and its impact on the field, along with novel clinical data
• Determining the current state of play: discussing what challenges remain, the current funding environment and the priority for the field to outline present focus
• What’s next? Discussing the potential for allogeneic or in vivo approaches, scalable manufacturing and expansion to novel patient populations
Delivering to More Patient Populations by Expanding HLA Coverage
3:00 pm Selection of High Affinity T-Cell Receptors from Large Fully Human Pre-Immune Yeast Libraries
Synopsis
• Soluble TCRs can co-opt peptide-HLA (pHLA) recognition to eradicate virally infected and cancerous cells but require high affinity for efficacy in clinically validated T-cell engager formats
• Native TCR repertoires are pruned by central tolerance, limiting the discovery of high-affinity TCRs against many therapeutic pHLA targets and posing a significant barrier to the development of soluble TCR-based therapeutics
• Designing and selecting the first fully human pre-immune TCR libraries built in yeast, facilitating the rapid and high throughput discovery of diverse high-affinity TCRs that retain target pHLA specificity, providing new opportunities for potent and specific therapeutics
3:30 pm Afternoon Break & Poster Session
4:00 pm Targeting Novel Epitopes & HLA Molecules to Expand Patient Populations
Synopsis
• Utilizing innovative platforms and mass spectrometry to find novel epitopes presented by frequent HLAs
• Validating the best TCR-HLA target combinations for clinical success
• Choosing the right HLAs to expand coverage to minority patient populations
4:30 pm Next-Generation TCRm TCE Therapeutics: A Paradigm Shift in Solid Tumor Immunotherapy
Synopsis
- TCRm targeting of undruggable intracellular proteins presents a unique opportunity for immunotherapy.
- T cell engagers (TCEs) are emerging as effective therapies for solid tumors.
- The Keyway TCRm Discovery platform provides an end-to-end workflow, delivering next-generation immunotherapies from target identification to clinical application
Boosting Biomarker & Companion Diagnostics for TCR Therapies to Optimize Patient Selection & Accelerate Clinical Success
5:00 pm Cross-HLA Targeting of Synthetic Neoepitopes with T-Cell Engagers to Eradicate KRASG12C Inhibitor-Resistant Cancers
Synopsis
• Development of high-specificity and high-affinity T-cell engaging bispecific antibodies (HapImmune antibodies) targeting KRASG12C inhibitor-modified HLA peptides (haptenpeptides, “p*MHCs”)
• Direct detection of p*MHCs by mass spectrometry, detailed target characterization, and demonstrated in vitro/in vivo activity of HapImmune antibodies
• Demonstration of the molecular-basis for cross-HLA recognition, examples spanning alleles within and across HLA supertypes
5:30 pm Leveraging Companion Diagnostics (CDx) to Distinguish Target Patient Populations
Synopsis
• Setting up your CDx tools early and evolving your CDx tools to cater to advancing clinical trials
• Understanding guidelines and retaining flexibility to adjust for changing diagnostics regulations
• Leveraging CDx to accelerate patient recruitment
6:00 pm A Toast to TCRs!
Synopsis
Round off your day at our drinks reception. Open to all, this is the perfect way to wind down with your peers with a glass in hand.