*All Times Shown in PST

7:00 am Breakfast Briefing: Challenges in Development and Implementation of Mouse Models for Evaluation of Novel T-Cell Based Therapeutics

  • Daniel Corey Founder, CERo Therapeutics
  • John Rossi Senior Vice President, Head of Translational Medicine, CERo Therapeutics

Synopsis

Join us in this breakfast briefing to hear from CERo Therapeutics in a short presentation on the challenges in development and implementation of mouse models for evaluation of novel T-Cell based therapeutics. This is your opportunity to discuss key issues and points raised in the presentation and ask your burning questions.

8:00 am Morning Chair’s Opening Remarks

  • Ismael Samudio Senior Director Cancer Biology & Translational Science, Notch Therapeutics

Expanding Your Pre-Clinical Model Toolbox

8:10 am Keynote: T Cell Based Therapies: Outlining Strategies for Enhanced T Cell Activation & Overcoming T Cell Exhaustion

Synopsis

• Suboptimal T cell activation and T cell exhaustion enables rapid tumor development: understanding the points in which T cell activation and exhaustion can be controlled
• Using IO therapies to enhance T cells function in the tumor microenvironment
• Exploring the lineage commitment of T cells as they progress towards terminal exhaustion: preventing versus reversing exhaustion

8:40 am Combination Approach: A Breakthrough In Vivo Model for High-Value Identification of Oncology Candidate

Synopsis

• How to use Inovotion’s technology to open new perspectives for in vivo screening in oncology and immuno-oncology
• Why Is the chick embryo model particularly well suited for drug discovery and early identification of high-value compounds in oncology
• Come and learn how to explore securing preclinical and clinical results using Inovotion’s model

9:10 am Seeing Your Tumor in Real Time: Advanced Imaging for Preclinical Studies

Synopsis

• Recognizing the importance of imaging and its ability to create visual data
• Addressing the issues surrounding quantification and pricing of imaging
• Exploring the window of expression: real-time imaging is an effective way of racking biomechanisms

9:40 am 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

9:55 am Morning Break

10:30 am Panel Discussion

Synopsis

• Discuss model selection for bispecific vs T-cell engager vs small molecule vs ADC

11:00 am Syngeneic Metastasis Models & Patient Derived Ex Vivo Models for Preclinical Applications

  • Viswanathan Muthusamy Director, Center for Precision Cancer Modeling & Research Scientist, Yale University

Synopsis

• Progress with syngeneic metastasis models in immuno-oncology
• What have we learned?
• Patient derived ex plant models – do they work in investigation of IO agents?
• Assessing the criteria for choosing these models

Maximizing Your Model Predictability

11:30 am In Vivo Efficacy & Toxicity Evaluation Using Various Humanized Mouse Models to Increase Clinical Translation

  • Jenna Frame Scientific Communications and Marketing, Biocytogen Boston Corp

Synopsis

• Discuss and evaluate IO target humanized mouse models, including hCD3e models for IO antibody efficacy evaluation
• How can cytokine/cytokine receptor humanized mouse models be used for better antibody translation?
• B-NDG-B2MKO – Considering the immune deficient mouse models for antibody, CART, NK-CART efficacy evaluation
• Outlining various disease models and surgical mouse models for gene therapy

12:00 pm Exploring In Vitro Assays & The Innate Immune Response

Synopsis

• Focusing on the innate immune response to develop more predictive models
• Establishing immune phenotype screening that translates in vivo

12:30 pm Networking Lunch

1:30 pm Advancing CAR-NK Cell Therapies Using Single Cell & Multiomics Computational Approaches

  • Sombeet Sahu Associate Director, Bioinformatics, Nkarta Therapeutics, Inc

Synopsis

• Explore computational approaches to characterize cell therapy products
• Utilize single cell tools and establish translational data analysis pipelines

2:00 pm Deconvoluting Cancer Immunotherapy in Humanized Mouse Models

Synopsis

• Human cells in the mouse body: are your immune cells responding to your therapy, or to the unique constraints they face in a hostile environment?
• Discussion of trade-offs between lead time, cost, and generation of cohorts for powered studies
• The benefit of getting your therapy into human cells; sometimes, why animal surrogates are not good enough

Deep Diving Into Preclinical Combination- IO Therapies

2:30 pm The Disease Model Finder: An AI Powered Platform to Enhance Disease Model Sourcing

Synopsis

  • Background on Scientist.com
  • Motivation for the Disease Model Finder
  • Interacting with the Disease Model Finder

2:45 pm Careful Selection of Combination Therapy to Ensure Creation of Models That Translate to the Clinic

Synopsis

• Finding the right combinations: stratification of patients based upon their mechanisms of immune evasion and how to mimic to identify treatment therapy
• Selecting patients: pinpointing your patient population and cross diagnosis. How the same combination therapy can treat patients with different cancers
• How do we create models and identify biomarkers that allow you to see the effects of combination clearly
• Creating a critical thought process about the biology of what you are combining to get the best efficacy of treatment

3:15 pm Afternoon Networking Break

Evaluating the Importance of the Dialogue Between Cells & Challenges Faced When Modelling the TME

3:45 pm Panel Discussion

  • Mark Orr Senior Principal Scientist, ImmunoOncology & Cellular Therapy, Bristol Myers Squibb
  • Markus Vallaster Executive Medical Director - Cell Therapies & Immuno-Oncology, AstraZeneca
  • David Messenheimer Senior Scientist, Pharmacology, Zymeworks

Synopsis

• Evaluating combination-IO therapy strategies and how to appropriately model them.

4:15 pm Evaluating and Addressing the Challenges of the TME in multiple Solid Tumor CAR T Cell Models

Synopsis

• The use of cyclophosphamide to modulate the suppressive TME in syngeneic mouse models to improve solid tumor CAR T cell therapy
• Using syngeneic models to properly identify potential of immune-modulators in combination with solid tumor CAR T cells
• Developing alternate murine CAR T cells and mouse tumor models expressing relevant tumor antigens found in human cancers

4:45 pm The Tumor Support Network: Stromal Compartment of TME

Synopsis

• Highlighting the importance of stromal compartment and naïve components of the immune system which have specialized roles in supporting the tumor
• Discussing how syngeneic models are lacking in their stromal compartment which does not accurately reflect human tumors
• Can we develop models to recapitulate the immune and stromal contexture of solid tumors to predict efficacy of I/O combinations in the clinic?

5:15 pm Unravelling the Tumour Microenvironment: Hypoxia Induced HIF-1a Expression in NK Cells Promotes Anti-Tumor Effector Functions

Synopsis

• Hypoxia in the TME is a major contributor to immune evasion in solid tumours. Whether HIF-1α is expressed in hypoxic NK cells in the context of IL-2 and if its expression regulates NK cell effector function was studied
• Human NK cell line NKL and ex vivo expanded NK cells
• expressed HIF-1α upon IL-2 stimulation in hypoxia and exhibited improved antitumour cytotoxicity and IFN-g secretion
• Ex vivo expanded human NK cells and NKL cells required the concerted activation of PI3K/mTOR pathway initiated by IL-2 signalling in combination with hypoxia for HIF-1α stabilization

5:45 pm Chairs Closing Marks & End of Summit