8:50 am Chair’s Opening Remarks

8:55 am

Enhancing the Translational Confidence of T Cell–Redirection Strategies

Synopsis

Multiple methodologies exist for directing T cells to tumor cells. Checkpoint, CAR and BITE’s have generated much excitement given the range and level of function they can elicit from T-cells as well as the expansion of treatment possibilities they present for immunotherapies. This session will look to review emerging preclinical strategies for predicting, mediating and mitigating toxicities.

9:00 am Validating IO Bispecific Antibodies in Humanized Models

Synopsis

  • Targets of the innate immune system are less evolutionarily conserved than the adaptive immune system, presenting challenges in pre-clinical testing
  • Use of genetically engineered models and humanized mice are novel approaches to test therapeutics to these targets
  • AL008 is a bi-functional antibody that antagonizes SIRPa, a myeloid checkpoint receptor, and activates Fc receptor signalling, and induces tumor regression as a monotherapy and a combination therapy in pre-clinical models

9:30 am SubQperior: A Superior Syngeneic Model System to Subcutaneous Tumor Models

Synopsis

Introducing the next generation of tumor models for immuno-oncology efficacy studies overcoming common problems experienced with subcutaneous tumor implantation

9:45 am IL12-Armored CAR-T: Multi-Dimensional Data Analysis to Assess both Efficacy & Safety Considerations in an NSG Mouse Model

Synopsis

• 4th generation “Armored” CAR-T cells express a biologic payload to assist in overcoming hostile tumor microenvironments

• Many payloads, such as IL12, have potentially toxic effects when dosed systemically

• Chimera’s proprietary GOLD CAR-T cells restrict the payload delivery to the local tumor microenvironment

• We used measurements of IL12 levels and other pro-inflammatory cytokines in the blood correlated with tumor burden and time-since-tumor-clearance to compare inducible verses constitutive IL12 delivery by CAR-T cells

• Combining a temporal analysis with quantitation of both payload and effector cytokines gives a more complete picture of the benefit of GOLD-controlled delivery of IL-12 verses constitutive delivery

10:15 am Morning Refreshments & Networking

3D Oncology Modeling & its Applications in IO

Synopsis

3D oncology modeling has seen a resurgence in recent times due to the versatility and cost-effectiveness they provide across a variety of cancers. This session will see speakers highlight the new capabilities that 3D models offer preclinical teams.

11:30 am The Potential of 3D Tumor Organoid Models in Testing ImmunoOncology Therapeutics

Synopsis

• Get an overview on the 3-D hydrogel system, particularly synthetic/ polymeric; PDX use in vitro; and microfluidic perfusion plates

• Discussing the incorporation of more immune components and IO aspects in our current model

12:00 pm Lunch & Networking

1:00 pm Modeling Immune Mediated Beta Cell Destruction in Human Type 1 Diabetes With Islet Organoids

Synopsis

• Organ-immune interactions are critical and often under-appreciated and we can derive important learnings from human organoid models for autoimmune diseases, some of which might be rather helpful for the tumor immunology field

• Islet beta cell stress is a critical component of immune destruction

• We have created, an islet organoid model that allows for precise evaluation of islet stress, also via imaging, and immune attacks. The key here is the reliability and small deviations of the system, which is assured by the microfluidic device and using organoids

1:30 pm Panel Discussion: Lifting the Lid on – 3D Oncology Modeling

Synopsis

• 3D modeling and its capabilities have been somewhat of a blind spot for
preclinical and translational oncologists. In this discussion we will lift the lid on
these models to reveal what the future may hold for research teams that are
looking to embrace these technologies
• As well as the capabilities, we will also consider the short comings and the areas
that are yet to be explored

2:00 pm Afternoon Refreshments & Networking

Modeling Strategies to Enhance the Translational Confidence of Immunotherapy Combinations

Synopsis

The renaissance in cancer immunotherapy is bringing with it added complexity for combinatorial drug development. Given the lack of predictiveness often attributed to current models, huge question marks still center around key study design elements such as dosing, scheduling, escalation strategies and patient
selection. This section will look to elucidate the understanding of the mechanism of action of tested
compounds and help with identifying rationale combination partners for best anti-tumor efficacy.

3:00 pm Supercharging the Tumor Microenvironment with the Engineered Cytokines NKTR-214 & KNTR-255

  • Loui Madakamutil Senior Vice President & Head of Discovery & Preclinical Development, Nektar Therapeutics

Synopsis

• The idea of combining the immune modulating properties of checkpoint inhibitors and other immunological medicines with the immune stimulating function of engineered cytokines is conceptually powerful

• Engineered cytokines can more effectively stimulate cytokine receptor pathways, while controlling adverse events

• The combination of NKTR-214 with Opdivo has demonstrated powerful anti-tumor effects and profoundly alters the tumor microenvironment, increasing effector T-cell counts, increasing PD-1 expression on tumor T-cells, and converting PD-L1 negative tumors to positive, while maintaining a more tolerable AE profile than traditional cytokine therapies

• NKTR-255, an IL-15 receptor agonist stimulates NK cells and CD8 memory T cells has the ability to be combined with monoclonal antibodies with ADCC function or with cellular therapies

3:30 pm Engage, Expand, Enable: Therapy of Established Tumors with Multiple Agents Targeting Diverse Immune-Tumor Interactions

  • Jim Hodge Deputy Chief, Laboratory of Tumor Immunology and Biology Senior Investigator, National Institutes of Health

Synopsis

• Animal model selection and therapeutic success is crucial to moving into clinical trials

• Optimal tumor therapy requires addressing multiple tumor-immune cell interactions

4:00 pm Chair’s Closing Remarks & Close of Conference