7:50 am Chair’s Opening Remarks
Assessing Current Modelling Limitations & Emerging Trends to Drive Clinical Success
8:00 am Combination of a Multimeric Anti-DR5 IgM Antibody with Targeted Agents Induces Synergistic Tumor Cytotoxicity in Vitro & in Vivo
Synopsis
- Death receptor 5 (DR5) is activated upon receptor trimerization and induces cell death. IGM-8444 is a multivalent IgM antibody that efficiently clusters DR5 to induce potency tumor cytotoxicity
- IGM-8444 has a good preclinical safety profile, enabling opportunities for rational combinations with targeted agents
- Synergistic combinations were identified in vitr
8:30 am Leveraging PDX-derived Organoid (PDXO) Models for Combination Targeted Oncology
Synopsis
- PDX-derived organoids are biologically equivalent to their matched PDX counterparts based on several shared characteristics
- Screening of PDXO in a combination matrix approach enables rapid and valuable insight into combination strategies
- A PDXO in vitro platform improves translatability of drug candidates, saves development time, and reduces animal usage by guiding optimal in vivo model selection for follow-on validation studies
9:00 am Translatability at a Glance: Combined Gene Edited & Engineered Cellular Therapies for Solid Tumors
Synopsis
- Creating and characterizing cellular therapies for targeting multiple cell surface receptors on tumor cells and TME
- Testing the efficacy of targeted cellular therapies in translatable tumor models
- Defining a roadmap towards clinical translation
9:30 am Leveraging the Power of Novel Humanized Models to Support Preclinical Oncology Studies in the Context of Changing FDA Pre-IND Requirements
Synopsis
- Utilizing translational pre-clinical models for progressing drug discovery
- Understanding clinical relevance of safety-tox in pre-clinical systems
- How Jax is pushing the boundaries of innovation in humanized mouse platforms in drug-discovery
10:00 am Patient-Derived Cell (PDC) Models as a Tool to Assess Cancer Therapeutic Efficacy Across the Drug Development Life Cycle
Synopsis
- PDC model development and characterization
- Clinical response predictivity
- HTS/HCI applications to assess cancer therapeutic efficacy, mechanism of action and patient stratification
10:30 am Morning Break & Structured Networking
Drug Discovery
Optimizing Technologies to Support Pre- Clinical Models
Track Chair: Jessica Haverkamp, Associate Director Macrophage Biology, BlueRock Therapeutics
Track Chair: Jessica Haverkamp, Associate Director Macrophage Biology, BlueRock Therapeutics
11:15 am Fireside chat: Utilizing RNA-Seq for Better Pre-Clinical Predictions & Patient Identification
Synopsis
- Screening for actionable targets based on targeted RNA-sequencing to make a more accurate prediction of drug efficacy
- How to preserve the complexity of tumor biology in models?
- Can we use RNAseq to understand MoA?
- Can we use baseline RNAseq readouts as patients selection? Is this practical with a gene signature, or do we need to limit this to 1-2 genes to make this practical in clinical trials?
11:45 am Humanized Mouse Model as a Translational Tool for Immunotherapy in Oncology
Synopsis
- Engineering human target in huPBMC GvHD model to construct a clinic translational model
- Deepen understanding of tumor biology and therapeutic response of multiple specific Nanobodies
- Donor selection and HLA match for improving treatment response
12:15 pm De-Risking Drug Development by Incorporating Clinically Correlated Ex Vivo Models
Synopsis
- Clinically correlated ex vivo models are available to provide solutions to historical problems such as efficacy
- Kiyatec’s models can be incorporated into every stage of drug development across multiple drug classes
- Preclinical development can lead to clinical utilization
12:30 pm Treatment Modalities to Improve Response in Tumors Refractory to Standard Immunotherapy Approaches
Synopsis
- Low dose radiation in combination with immunotherapy in advanced tumors
- Mechanistic insights into radioimmunotherapy resistance
- Reversing immune dysfunction via interference of TGFbeta pathway with inhibitors of the integrin avB8
1:00 pm Q&A
Drug Development
Exploring Approaches to Dosing & Combination Administration Methods
Track chair: Katie Grausam Postdoctoral Scientist, Cedars Sinae
Track chair: Katie Grausam Postdoctoral Scientist, Cedars Sinae
11:15 am Targeting c-MET in Combination with Radiation is Effective in MET-Fusion Driven High- Grade Glioma
Synopsis
- Inhibitor and radiation regimen selection for combinatorial in vivo trials
- Validating preclinical results in multiple mouse models
- Complementing in vivo data with PK and in vitro analyses
11:45 am Combination Therapy to Outsmart RASAddicted Cancer – Informing Clinical Strategy with Preclinical Modeling
Synopsis
- Identify biomarkers that can help direct the “right combination regimen” to the “right patients”
- Define upfront combination regimens that can prevent/ delay emergent resistance mechanisms to RevMed RAS(ON) inhibitors
- Understand if/how we can translate learnings between distinct RAS mutations and cancer histotypes
12:15 pm Exploring Tumor Localized CD137 Agonism with Bicycle Tumor-Targeted Immune Cell Agonists (Bicycle TICAs®)
Synopsis
- Description of the development of tumor-targeted immune cell agonists (Bicycle TICA™) based on constrained bicyclic peptides (Bicycles®) to activate costimulatory receptors selectively in the presence of tumor cells
- Outlining the preclinical mechanistic data underlying the profound reprogramming of the tumor immune microenvironment
- Highlighting translational aspects of work to inform clinical trials
12:45 pm Roundtable Discussion: Right Tumor, Right Model, Wrong Drug
Synopsis
- Getting the system right to evaluate drug utility
1:15 pm Networking Lunch
2:15 pm Precise and translational preclinical models for assessment of immune-targeting agents
Synopsis
- Outlining BRGSF-HIS mice: immunodeficient mice displaying functional human lymphoid and myeloid compartments, without side effects
- Assessing efficacy and toxicity induced by immune checkpoint inhibitors, cell engagers and combo therapies in BRGSF-HIS mice, which displays a wide therapeutic window
- Showcase of assessment of immune targeting agents in immune checkpoint humanized models
Tackling Metastasis: Modelling, Prevention & Treatment
2:45 pm Modeling Bone Metastasis of Prostate Cancer
Synopsis
- Develop mouse models to understand the way tumors metastasize and respond to therapy
- What determines metastatic competency? Can we predict this by studying primary tumors?
- What is the role of biomarkers to predict disease progression?
3:15 pm Session Reserved for Labcorp
Synopsis
- Cloudman S91 and YUMM1.7 melanoma models were evaluated following treatment with anti-mPD-1 and radiation therapy (RT) using flow cytometry and the NanoString® nCounter PanCancer IO 360™ panel
- Cloudman S91 tumor growth was sensitive to checkpoint inhibition but not RT, while TUMM1.7 tumors responded only to RT
- Treatment-induced immunophenotypic profiles and signaling pathway signatures were distinct between the two models and reflected the
corresponding tumor growth kinetics, thus providing two unique preclinical tools for drug discovery
3:30 pm Afternoon Break & Poster Session
Synopsis
Come and join us for the poster presentation session, and vote for your favorite
3:50 pm Accelerating Antibody Research Using Humanized Mouse Models
Synopsis
- Humanized components of the immune/oncology checkpoint pathways
- Models for bi-specific antibody development
- Next generation immunodeficient mice (NCG) for xenografts and better stem cell engraftment
4:20 pm Developing Clinically Translatable Models that Accurately Represent Patient Metastasis
Synopsis
- Understanding physiological routes of metastasis
- Identifying factors that influence dissemination
- Understanding how the microenvironment contributes to metastasis
4:50 pm Preclinical Evaluation of Novel Combination Therapies Using Multigenic Humanized Models
Synopsis
- Introduce the use and advantages of humanized syngeneic mouse tumor models for evaluating preclinical efficacy, toxicity, and other mechanisms of action of antibody/biologic combination therapies
- Outline the use of cell lines expressing tumor-associated antigens to evaluate dual checkpoint and TAA blockade in immune-checkpoint humanized mice
- Describe the applicability of human immune system humanized mice, which includes highly immunodeficient (B-NDG) mice and second-generation B-NDG models with humanized cytokines to support human immune cell subpopulations, for evaluating immunotherapies against human tumor cells