*All Times Shown in PST

7:15 am Morning “Coffee Room” Networking

7:45 am Breakfast Workshop: Software Solutions for the Animal Study Reproducibility Crisis and Enhanced Animal Welfare

Synopsis

In this breakfast workshop the following points will be discussed:

  • Causes and impacts of animal study irreproducibility on preclinical research.
  • Publicly-available and online resources and practically-applicable concepts, such as the ARRIVE guidelines, PHISPS protocols, and the N3R Design Assistant.
  • First-hand experiences with a variety of in-house-built and commercially-available animal study workflow software applications and databases and their direct and indirect impacts on the problems contributing to animal study irreproducibility.
  • Exploration of Studylog Animal Study Workflow Software as applied to improving study reproducibility and preserving detailed study results for future access.

You will walk away with an understanding of the factors that contribute to the crisis of poor preclinical study reproducibility, as well as

  • Gripping with principles and practices for better study design and conduct
  • Learning what animal study workflow software is really like in its’ practical application
  • Understand how it makes standardized study design, conduct and analysis much easier, faster, yet more detailed
  • Assess how the software does the researcher’s usual heavy-lifting for them, effortlessly facilitating protocol and procedural oversight, animal welfare compliance, push-button and real-time results analysis, reporting and graphing, task scheduling, all while preserving data securely for stakeholder access

Hosted by Studylog

8:53 am Chair’s Opening Remarks

Accelerating the Clinical Translation of I/O Candidates through Development of Novel Humanized Mouse Models

9:00 am Patient-Derived Tumor Xenografts in Humanized NSG-SGM3 Mice: A New Immuno-Oncology Platform

  • Basile Siewe Director - Business Development, The Jackson Laboratory

Synopsis

  • The addition of 3 human cytokines (GM-CSF, IL-3 & Kit Ligand) into the NSG mouse provides for a more robust myeloid compartment  after humanization
  • Showcase data on the myeloid engraftment kinetics and also show checkpoint inhibitor efficacy against several PDX
  • Leverage humanized mice to assess the risk of immunotherapeutic-associated cytokine release syndrome CRS)

9:30 am Fully Synthetic Tumor-Targeted Immune Cell Agonists (TICAs) Induce Anti-Cancer Immunity Through Tumor Localized CD137 Agonism

Synopsis

  • We have developed tumor-targeted immune cell agonists (TICAs™) based on constrained bicyclic peptides (Bicycles®) by linking Bicycles against costimulatory receptors (e.g. CD137) to those against tumor antigens (e.g. EphA2) creating potent agonists that activate costimulatory receptors
    selectively in the presence of tumor cells
  • Humanized (huPBMC) tumor xenograft models, as well as transgenic huCD137 syngeneic mouse tumor models, have been instrumental in the preclinical development of TICAs
  • Treatment of tumor antigen-expressing tumors in immunocompetent mice with TICAs lead to profound reprogramming of the tumor immune microenvironment including increased T cell infiltration and increase in cytotoxic cell gene signature. This leads to cytotoxic T cell-dependent
    complete tumor regressions and resistance to tumor re-challenges
  • Despite fairly short plasma half-lives in mice (1 – 2h), intermittent dosing of TICAs is very effective indicating potential for a wide therapeutic index in humans

9:50 am Next Generation Humanised NOG-EXL Mouse – Defining Variations within the Context of a Checkpoint Inhibitor Efficacy Study

Synopsis

  • Appropriate expression levels of human cytokines (GM-CSF, IL-3) provide a better model for improved reconstitution of human myeloid compartment in the NOG mouse
  • Showcase data on the degree of variance between stem cell donors, tumor types, and immune cell reconstitution (tissue, phenotype and/or kinetics) within a huNOG-EXL lung cancer model
  • A comprehensive perspective of multiple human lineages and multiple tissues that demonstrates the importance of proper power analysis, tumor type, timeline, and HSC donors for improved immuno-oncology in vivo efficacy studies

10:20 am Discussion/Q&A

10:40 am Speed Networking

Synopsis

Grab a cup of coffee and a bite to eat from the comfort of your own kitchen or office and virtually connect with new contacts and active companies in the preclinical I/O space. Exchange digital business cards,
catch-up with colleagues and strike long lasting connections using our unique speed networking feature.

11:10 am Morning Refreshments

11:40 am Dynamic Single-Cell Imaging of Cell-Based Immunotherapies using Human Xenograft Engraftment into Immune-Deficient Zebrafish

Synopsis

  • Development and use of immune deficient zebrafish for xenoengraftment of human tumors and assessing CAR-T, BiTE, and APECmediated immunotherapies
  • Dynamic live cell imaging approaches for early end point analysis and screening for new antibody therapies
  • EGFR as a target for cell-based therapies in rhabdomyosarcoma

12:00 pm Efficacy and irAE Assessment of Therapeutic Antibodies with Target Specific Knock-In Models

  • Dean Campbell Director – Scientific Engagement, Crown Bioscience

Synopsis

  • Use of humanized genetically engineered mouse models (huGEMM) to look at efficacy of immune modulatory therapeutics
  • Initial pre-clinical assessment of irAE using huGEMM models

12:20 pm Discussion/Q&A

12:40 pm Roundtable Lunch

  • Gerold Feuer Consultant- Industry Pioneer for Humanized Mice, Crown Bioscience
  • Dean Campbell Director – Scientific Engagement, Crown Bioscience
  • Alwin Schuller Senior Principal Scientist, AstraZeneca

Synopsis

• Do you use humanized/HuGEMM mice to investigate other aspects of your therapeutic besides efficacy?
• At what stage of the drug development workflow should we start to
investigate any potential irAE toxicity of immunotherapies?
• What are your thoughts on using humanized/HuGEMM mice to investigate irAE?
• What are some of the models used to investigate immunotoxicity?

Advancing Syngeneic Models for Accurate Assessment of Pre-Clinical I/O Candidates

1:30 pm Anti Tumor Activity of the Novel Arginase Inhibitor AZD0011 in Syngeneic Tumor Models, & Tumor Genetics Shape the Immune Landscape in Humanized Mouse Models

Synopsis

  • Developed a novel arginase inhibitor, AZD0011 that in vivo shows a time and dose dependent PK and PD and several signs of immune activation
  • AZD0011 shows single agent anti-tumor activity in various syngeneic tumor models and can be combined with various therapies including checkpoint inhibitors
  • Development of humanized mouse models show distinct immune subset engraftment in bone marrow and spleen, and robust engraftment in PDX tumors

1:50 pm Improved Antitumor Activity of Local immunotherapy with mRNA Encoding Cytokines and Immune Checkpoint Blockade in Multiple Preclinical Syngeneic Tumor models with “Cold” and “Hot” Immune Phenotype

Synopsis

  • Anti-tumor activity of intratumoral cytokine mRNA therapy in combination with immune check blockade in 12 syngeneic mouse models with “cold” and “hot” immune phenotypes
  • Immune mediated mechanism of action of combination therapy with cytokine mRNA and anti-PD-1 antibody

2:10 pm The Role of Biomarkers in the Transition from Preclinical Models to Clinical Trials in Immuno-Oncology

Synopsis

  •  Overview of different biomarkers and their functions
  • Preclinical immuno-oncology models and biomarkers
  • Brief discussion of biomarkers in immuno-oncology clinical trials

2:25 pm Discussion/Q&A

2:45 pm Virtual Poster Session

3:00 pm Afternoon “Coffee Room” Networking

Accurately Recapitulating the Tumor Microenvironment in I/O Models to Improve Clinical Translation

3:45 pm Modelling Tumor Microenvironment for Immuno-Oncology: Challenges and Opportunities

Synopsis

  • Immuno-Oncology therapies depend on accurate assessment of patient tumor microenvironment
  • Current challenges in functional modelling of tumor microenvironment
  • Tools and approaches to successfully reconstruct tumor microenvironment

4:05 pm Orthotopic Patient-Derived-Xenograft Models Guide Individualized Precision Oncology Therapy

Synopsis

  • Orthotopic PDX (O-PDX) models can be derived from needle or surgical biopsiez
  • In vivo pharmacology studies accurately predict patient response
  • The O-PDX methodology provides a platform for autologous
    humanization and precision IO studies

4:20 pm Genetically Engineered Mouse models of Brain Cancer: Preclinical Platforms for Testing Immunotherapies

  • Maria Castro Professor – Neurosurgery & Cell Developmental Biology, University of Michigan

Synopsis

  • Description of the tools and methodologies to develop the genetically engineered immune-competent glioma mouse models
  • Phenotypic and molecular characterization of the models and generation of 3D stem cell like neurosphere cultures of the tumor cells
  •  Data related to the tumor immune microenvironment and implementation of immunotherapies, and efficacy and toxicity outcomes

4:40 pm Discussion/Q&A

5:00 pm Industry-Focused Panel Discussion

  • Brian Soper Senior Manager - Technical Information Services, The Jackson Laboratory
  • Virna Cortez-Retamozo Senior Principal Scientist, Sanofi
  • Goutham Narla Professor - Medicine, University of Michigan
  • Darrell Borger Associate Director, Translational Oncology & Head, Integrated Translational Technologies, Takeda

Synopsis

During development of new immuno-modulatory therapeutics, when is the best time to evaluate cytokine release?

Options include:

  • As a stand-alone assay comparing molecules in a side-by-side assay for lead
    selection
  • During analysis of preclinical efficacy as part of the overall mode of action
  • Later stage, post preclinical efficacy to determine safety/tox prior to IND filing.

5:30 pm Closing Remarks & End of Conference Day One