Conference Day Two
Thursday, April 25
7:00 am Check-In & Coffee
7:55 am Chair’s Opening Remarks
8:00 am Breaking Ground: Revealing Novel Targets in Solid Tumors
Synopsis
- Explore strategies for identifying and characterizing novel targets within the complex microenvironment of solid tumors, opening new avenues for therapeutic intervention
- Delve into unconventional approaches and emerging technologies that enable the discovery of unique and previously unrecognized targets, revolutionizing our understanding of solid tumor biology
- Validating targets and TCRs for optimal therapeutics impact while mitigating cross-reactivity and ensuring safety
8:25 am Improving Efficacy and Minimizing Safety Risks of TIL Cell Therapy by Rational Engineering of TIL
Synopsis
• Conventional unengineered TIL cell therapy requires the use of IL2, which is associated with T-cell exhaustion, reduced cytotoxicity, and increased immune-inhibitory regulatory T cells, thus diminishing its therapeutic potential and resulting in substantial clinical toxicity that limits the eligible patient population.
• OBX-115 engineered TIL cell therapy utilizes Obsidian’s cytoDRiVE® platform to enable regulation of functional membrane-bound IL15 by reversibly modulating protein stability, enabling a lower dose of lymphodepletion than conventional unengineered TIL cell therapy, obviating the need for IL2 administration, and providing the ability to regulate antigenreactive TIL expansion.
• In an optimized and proprietary process, OBX-115 can be successfully manufactured from core needle biopsy tumor tissue, avoids the use of IL2 for rapid expansion, and delivers an optimized cytotoxic T-cell product with a high proportion of tumor-directed clones.
• In a first-in-human study, the OBX-115 treatment regimen has produced a 50% response rate in the first 6 patients, including 2 complete responses and a partial response, without any dose-limiting toxicities or Grade 4 treatment-emergent non-hematologic toxicity.
8:55 am Regulatory Odyssey of TCR Therapies: Navigating Safety, Efficacy, and Global Compliance
Synopsis
• Delve into the critical regulatory measures to ensure patient safety throughout the development, manufacturing, and administration of TCR therapies
• Efficacy Evaluation Strategies: Explore the regulatory considerations in designing robust clinical trial methodologies to assess the efficacy of TCR therapies, with a focus on meaningful endpoints and study design
• Discuss the challenges and importance of harmonizing regulatory standards globally to facilitate the development, approval, and post-marketing surveillance of TCR therapies on an international scale
9:20 am Rapid engineering of soluble T cell receptors for enhanced affinity via a high-throughput yeast-based platform
Synopsis
• Soluble T cell receptor (TCR)-based CD3 bispecific therapeutics can co-opt T cell function to eradicate virally infected and cancerous cells via peptide-HLA (pHLA) recognition.
• Native TCRs require extensive affinity maturation for efficacy in clinically validated CD3 bispecific formats, posing a significant barrier to the development of soluble TCR-based therapeutics.
• Adimab has developed a high-throughput yeast-based platform to rapidly generate and characterize TCR variants with substantially improved affinities and functional potencies while retaining target specificity.
9:50 am Morning Refreshment Break & Speed Networking
10:50 am Protein Engineering with Machine Learning (ML) for Specificity-Guided Development of Soluble TCR Engagers
Synopsis
• Specificity-guided affinity maturation. High sensitivity functional screens identify problematic off-targets early on
• Expansion of the physically screenable sequence space with ML models. Coupling highthroughput data generation with ML predicts affinity- and specificity-enhanced variants
• Activity-guided selection of optimal molecular format. Functional screening of TCR format library identifies optimal TCR-immunoligand configurations
11:15 am Enhancing TCR Selection: High-Throughput Wetlab Discovery & Machine Learning, & Advanced Computational Approaches for Optimal TCR-based Therapies
Synopsis
• High-throughput wetlab discovery of highly potent natural TCRs targeting novel and well-characterized antigens
• In silico TCR discovery integrating machine-learning-based specificity prediction from T-cell profiles, ultrafast sequence similarity search, and structure-guided prioritization for efficient candidate selection
11:40 am Unlocking Potential: Using Non-Viral DNA Vectors for TCR Engineering
Synopsis
• Explore how non-viral vectors mitigate risks associated with insertional mutagenesis, ensuring safer TCR-T therapies
• Discuss the streamlined clinical-scale manufacturing processes of non-viral methods, reducing costs, accelerating production timelines, and reducing complexities in TCR-T cell therapy development
• Delve into the controlled gene expression and broader applications for DNA Vectors, enabling more efficient, economical, and safer genetic engineering of cells
12:05 pm Lunch Break & Networking
1:05 pm A multi-specific multi-functional CD4+ T cell therapy for solid tumors for superior safety and efficacy in immunotherapy
Synopsis
• A distinct type of CD4+ T cells in tumor immunity—CD4 CTLs with both cytotoxicity and helper functions
• Producing CD4 CTLs with natural TCRs targeting multiple antigens for immunotherapy in solid tumors
• Multi-specific CD4 CTLs are poised for superior safety and efficacy in immunotherapy
1:30 pm Safeguarding Therapeutic Precision: Mitigating Toxicity in TCR-T Therapy
Synopsis
• predicTCR – a machine learning classifier for rapid, scRNAseq- based identification of tumor-reactive T-cell receptors for personalised T-cell therapy
• Discuss strategies to identify patient-specific tumor-reactive TCRs for personalized T cell therapy
• Manufacturing personalized TCR-transgenic T-cells: explore methodologies ensuring clinically viable turnaround times
• Regulatory challenges: discuss potential solutions for implementing perosnalized TCRtransgenic T-cell therapies
1:55 pm Developing TCR-T cell Therapy for Patients with HIV and HPV-Associated Cancer: Extending a Promising Therapy to Underrepresented Groups
Synopsis
• Adoptive T cell therapy shows promise but often excludes HIV-positive individuals from cancer trials.
• Evidence suggests full-dose chemotherapy and immunotherapy are safe for HIV positive cancer patients.
• Retrospective studies indicate comparable safety and efficacy of CD19 CAR T cell therapy in people with HIV and B-cell malignancies.
• We aim to test the safety and efficacy of E7 TCR-T cell therapy in HIV-positive individuals with HPV-associated cancer, an underrepresented group in the US.
2:20 pm Conquering the Tumor Microenvironment: Harnessing TCRs for Therapeutic Success
Synopsis
• Strategies for enhancing TCR-T efficacy: improving in vivo performance of TCR-T cells through TOOLBOX-engineering
• Tackling the tumor microenvironment (TME): arming TCR-T cells to overcome the immunosuppressive nature of solid tumors
• Speeding up tumor rejection: enabling TCR-T cells to take up the fight against solid tumors quicker
2:45 pm Afternoon Refreshments & Networking
3:15 pm Harnessing Anti-Tumor Myeloid Cells With Armored TCR-T Cells in the Solid Tumor Microenvironment
Synopsis
• Explore how myeloid cells can be converted from pro- to anti-tumor phenotypes and play a pivotal role in creating a supportive microenvironment.
• Immune activation, Microenvironment Remodeling and immune Suppression Reversal
• Ensuring safety of this approach
Cutting-Edge Innovations in TCR Engineering: Pioneering Precision & Resilience in Cancer Therapy
3:40 pm A Novel Generative AI-Designed T-Cell Receptor Bispecific for Cancer Immunotherapy
Synopsis
- Application of the proprietary machine learning platform, EMLyTM , for TCR discovery leading to the generation of a lead PRAME TCR
- TCR engineering using EMLyTM for rapid affinity enhancement of the parent molecule by more than 5 million-fold
- Development of a functional TCR bispecific from this lead molecule, and current advancement towards preclinical phase
4:05 pm CBX-250: A First-in-Class TCR-Mimetic-Based T-Cell Engager for the Treatment of Myeloid Leukemia
Synopsis
- Introduce a novel TCR-mimetic based T-cell engager against a novel target in AML and other myeloid malignancies
- Discuss the preclinical characterization strategy and results of target safety, binder potency, binder specificity and TCE developability
4:30 pm Fortifying Precision: Cell Armoring in TCR-T Therapy for Solid Tumors
Synopsis
- Discover how cell armoring techniques aim to fortify TCR-T cells, enhancing their resilience and persistence within the hostile microenvironment of solid tumors
- Discuss the potential of cell armoring in elevating the precision of TCR-T therapy