Agenda
7.30 am Registration & Coffee
8:30 am Chair’s Opening Remarks
Sharing Advances in the Clinical Development of Gamma Delta Therapies to Drive Response in Solid Tumors
8:45 am Panel Discussion: Industry Leaders’ Year in Review: What Have We Learned This Year, & Where is the Field Heading in 2023?
Synopsis
- Considering how therapeutic approaches to harness gamma delta T cells can rival alpha beta approaches
- Discussing how to progress to the clinic faster and attract interest from pharma companies to fund scaled trials
- Identifying the greatest areas of opportunity and key challenges to the industry in gamma delta T cell development
- Discussing the future opportunity to improve scalability of engineered products to drive solid tumor success and long-term therapeutic effect
9:30 am Sharing Clinical Updates of ADI-001, a ‘First-in-Class’ Allogeneic CAR-Engineered Gamma Delta T Cell Therapy to Demonstrate Safety & Persistence
Synopsis
- Deep-diving into clinical updates and safety and persistence data from ADI-001’s first year in the clinic
- Reflecting on the lessons learned to take into phase 2 clinical trial design, dose escalation, patient selection, pharmacodynamics, and safety
- Discussing future opportunities in the pipeline to expand into more indications and impacts on other areas of R&D
10:00 am Revealing Phase 2 Results of ICT01, a Gamma Delta 2 T Cell Activator, to Demonstrate Clinical Potential in Solid Tumor Settings
Synopsis
- Sharing the first phase 2 data of a gamma delta 2 activator as a monotherapy and in combination with checkpoint inhibitor
- Identifying patient populations with clinical rationale to align with the mechanism of action to advance efficacious therapies to the clinic in the right patients
10.30 am Morning Break & Speed Networking
Research & Translational Development
Characterizing Gamma Delta T Subsets & Mechanisms to Inform Therapeutic Application
11:30 am Revealing the Metabolism and Signalling Mechanisms of CAR-Engineered Gamma Delta T Cells to Improve Design Strategies
Synopsis
- Exploring the metabolism and behaviour of gamma delta T cells
- Interrogating the mechanism of CAR signalling in a gamma delta T cell product
- Recapitulating intercellular interactions of gamma delta T cells and discussing how they can be harnessed to enhance product design
12:00 pm Virtual Talk: Innovating Novel Humanized Preclinical Mouse Models to Validate Gamma Delta T Therapy
Synopsis
- Developing humanized mouse models with CD34 constituted mice to study the in vivo function of gamma delta T cells
- Using models to model in vivo pharmacology and inform preclinical study designs
- Bridging the gap between preclinical models and in vivo human studies with better mouse models
- Appreciating model limitations and discussing strategies to maximize preclinical workflows and provide confidence in clinical translation
12:30 pm Mice with precise replacement of human gamma/delta T cell receptors generate TCR as efficiently as normal mice and their immune response to human cancer and pathogenic antigens
Synopsis
- Targeted generating humanized TCR Vδ1-8, along with human Ds and Js and human TCR Vγ1-11, along with human Js.
- Expression of the human Vδ1-6 was found in many tissues. Human Vγ9Vδ2 was also found in the murine blood. Tens of thousands of human CDR3s were identified by NGS analysis.
- These humanized mice were challenged with pathogenic sources of live E. coli and Staphylococcus aureus extract which led to TCR clonal emerging and focusing of the human Vδ1, Vδ2, Vδ4, and human Vγ9.
- Incubation of these humanized g/d T cells with human cancer cell lines resulted in the release of cytokines. These mice could provide a powerful new model for infectious diseases, cancer, inflammation, autoimmune disease, and neurological disorders.
12:45 pm Examining the Regulation of Tumor Homing to Identify Therapeutic Strategies to Enhance Traffic to Site
Synopsis
- Understanding how gamma delta T homing is naturally regulated, exploring novel targets and CARs against paediatric tumors
- Evaluating how chemotherapy can lead to increased tumor stress, and the applications of this for combined gamma delta T therapies
- Identifying targets to engineer or combine therapies to enhance tumor homing and infiltration
- Discussing the pros and cons of using engineered vs. combination strategies and how to most suitably evaluate both approaches
Clinical & Product Optimization
Demonstrating Clinical Activity to Cement Product Design & Mechanism of Action
11:30 am Analyzing Clinical Biomarker Data from Solid & Liquid Tumor Biopsies to Characterize Subset Distribution & Inform the Clinical Strategy for Gamma Delta T Therapy in Different Indications
Synopsis
- Reviewing biological mechanisms, subset populations, and clinical biopsy data to suggest the most appropriate indications to deploy gamma delta T therapy
- Discussing the variety of combinations suitable for different indications based on biopsy data
- Applying learnings from biopsy data to leverage gamma delta T populations as a biomarker for prognosis
12:00 pm Demonstrating Preclinical Activity with Xenograft Models to Indicate Solid Tumor Efficacy of TGFb Educated Gamma Delta T Therapy in Concert with IL18 Stimulation
Synopsis
- Advancing patient-derived xenograft models to demonstrate gamma delta T efficacy and mechanism of action for CAR engineered gamma delta T with latent IL18
- Bridging the gap between xenograft models and in-human trials, and discussing the limitations and best applications to move into the clinic with confidence
- Considering whether you can sustain gamma delta T in xenograft models to reduce tumor burden in mice, and how much of a reflection of in vivo activity this is
12:30 pm Leveraging Biometrics & Biostatistical Analysis to Understand Therapeutic Impacts on Tumor Progression
Synopsis
- Correlating PKPD with tumor physiology and cell aggregation to conclude anti-tumor impacts
- Sharing a sequencing analysis method to explore physiological impacts on the tumor microenvironment
- Harnessing sequencing to detect early signs of GvHD to prevent clinical setbacks and lift early barriers to trial progression
1:00 pm High-Resolution Immune Profiling and Machine Learning for Donor Selection, Product Characterization and Patient Monitoring
Synopsis
- High-resolution immune profiling and donor selection to improve production efficiency
- Better understanding of product characteristics and heterogeneity through scaleable high-resolution profiling
- Systems-level immune monitoring for clinical trials
1.15 pm Lunch & Networking
Research & Translational Development
Engineering Receptors to Enhance Efficacy, Specificity & Persistence
2:15 pm Comparing Different Constructs to Identify the Optimal CARs & TCRs for Improved Efficacy & Persistence of Gamma Delta T Cells
Synopsis
- Testing the addition of an αβ CAR to a TCR gamma delta T versus a gamma delta T-tailored CAR
- Contrasting the impact on memory cells and cell proliferation and exhaustion
- Testing the impact of construct design on persistence of cells and therapeutic response
2:45 pm Discussing the Preclinical Development of Gamma Delta T Cells Engineered with the T-cell Antigen Coupler (TAC) for the Treatment of Solid Tumors
Synopsis
- Introducing TAC engineering as an alternative tool to the CAR to persistently drive tumor killing
- Sharing preclinical data that inform on product characteristics, mechanism of action and potency
- Evaluating the pharmacology from preclinical studies, and outlining next steps in the clinic
3:15 pm Incorporating Drug Regulated Switch Modules to Improve the Safety of Cellular Therapies
Synopsis
- Engineering small molecule regulated protein switches for remote control of cellular therapies
- Capitalizing on regulation of CAR function with small molecule drugs
- Understanding safety considerations needed with increasingly potent cell therapies in vivo
Clinical & Product Optimization
Interrogating Pharmacokinetics & Combination Studies to Drive Clinical Outcomes
2:15 pm Maximizing the Clinical Effects of Gamma Delta T Cells: Evaluating Stand Alone & Novel Combination Therapy Approaches
Synopsis
- Considering γ9δ2 T cell-activating mAb and γ9δ2 T cell engager reliance on the endogenous pool of γ9δ2 T cells: Is there a minimum or optimal number required for successful monotherapy?
- Discussing the rationale for novel combination approaches being tested in the clinic to improve the therapeutic effects of a γ9δ2 T cell-activating mAb
- Combining of gamma delta T cell-based therapies with a γ9δ2 T cell-activating mAb or a γ9δ2 T cell engager – could this be the most effective approach?
2:45 pm Translating a Lab Scale IPSC-Derived Gamma Delta Process to a Clinically Relevant Manufacturing Approach
Synopsis
- Developing vertical process parameters to ensure reliable and reproducible process performance
- Increasing scalability of iPSC-derived gamma delta T cells
- Achieving a ready available, off-the-shelf source of consistent gamma delta T cell therapy
3:15 pm Designing a Dosage Schedule to Optimise Persistence & Provide Durable Clinical Responses
Synopsis
- Understanding the mechanism of action of gamma delta T cells to justify repeat dosage and understand systemic and local responses
- Optimizing dosage through size, frequency, and intervals to minimise side effects, improve tolerability and deepen response in solid tumours
- Using preclinical data to support first-in-human clinical trial design
3.45 pm Afternoon Refreshments & Networking
Reviewing Clinical Developments & Approaches to Maximize the Therapeutic Niche
4:15 pm Panel Discussion: What Needs to be Done to Fully Capitalize on the Promise of Genetic Engineering to Produce Scalable & Clinically Efficacious Gamma Delta T Cells?
Synopsis
- Debating the need for genetic engineering to enable strong clinical results
- Comparing and contrasting the need for CARs or other types of gene engineering to enhance efficacy
- Leveraging different engineering technologies to equip gamma delta Ts with the genetic capabilities to maximize persistence
5:00 pm Chair’s Closing Remarks
5:15 pm End of Day One
5:30 pm
Drinks Reception & Poster Session
Synopsis
Join us for drinks and a scientific poster session to network with gamma delta leaders in a more informal setting!