*All Times Shown in PST

7:15 am Registration & ‘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

8:55 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

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

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 Speed Networking & Morning Refreshments

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 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

11:30 am Patient-Derived Experimental Models for Translational Cancer Research

Synopsis

  • Patient-derived organoids (PDO) and Patient-derived xenografts (PDX) are patient-relevant platforms for efficacy evaluation of cancer therapeutics
  • PDX-derived organoids (PDXO) is a new in vitro platform featuring both patient relevance and scalability
  • Leveraging our extensive PDX collection to run surrogate clinical trials in a preclinical setting

12:00 pm Discussion/Q&A

12:30 pm Roundtable Lunch With Covance

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

1:30 pm AZD0011 Shows Immune Activation & Anti-Tumor Activity as Mono- & Combination Therapy in Syngeneic Tumor Models

Synopsis

  • Developed a novel arginase inhibitor (AZD0011) able to reverse arginase induced immune suppression in vivo
  • Inhibition of arginase by AZD0011 increases the number and activation of intra-tumoral cytotoxic T-cells and NK cells
  • Arginase inhibitor AZD0011 shows combination activity with various immune-activating strategies including checkpoint inhibitors and TLR agonists

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

2:30 pm Discussion/Q&A

2:50 pm Afternoon Networking & Poster Session

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

3:40 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

4:00 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

  • Zhao Chen Principal Scientist, Novartis
  • Jonathan Nakashima Chief Scientific Officer, Certis Oncology
  • Maria Castro Professor – Neurosurgery & Cell Developmental Biology, University of Michigan

5:00 pm Closing Remarks & End of Conference Day One

5:10 pm Digital Drinks Reception hosted by The Jackson Laboratory