*All Times Shown in PST

8:00 am Registration & ‘Coffee Room’ Networking

8:50 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

  • James Keck Senior Director - Innovation & Product Development at JMCRS, 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

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 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.

10:50 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

11:10 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

11:40 am Discussion/Q&A

  • Goutham Narla Professor - Medicine, University of Michigan
  • Johanna Lahdenranta Director – In Vivo Pharmacology, Bicycle Therapeutics
  • James Keck Senior Director - Innovation & Product Development at JMCRS, The Jackson Laboratory
  • Dean Campbell Director – Scientific Engagement, CrownBio
  • David Langenau Professor , Massachusetts General Hospital

12:10 pm Roundtable Lunch With Covance

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

1:10 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

1:30 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

1:50 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

2:10 pm Discussion/Q&A

2:40 pm Afternoon Networking & Poster Session

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

3:30 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

3:50 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

4:10 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

4:50 pm Discussion/Q&A

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

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