9:15 am Chair’s Opening Remarks

Identifying Immune Mechanisms to Modulate Myeloid Cell Behavior for Therapeutic Benefit

9:30 am Removing Myeloid Inhibitory Signals to Enable Anti-Tumor Response & Restore Immune Activity

  • Barbara Platzer Senior Principal Scientist, Novartis Institutes for BioMedical Research

Synopsis

• Charting signaling, inhibitory, and excitatory pathways of myeloid cell populations to identify novel cascades of therapeutic value

• Sharing lessons learned from MCSF receptor inhibition in the clinic to modulate MDSCs and macrophages

• Developing TIM3 therapies as a checkpoint for both myeloid and T cells, and discussing the mechanism of action and therapeutic rationale

10:00 am Modulating Myeloid Cell Functionality via the SIRPa-CD47 axis and Novel CLEC1 Checkpoints to Bridge the Adaptive and Innate Immune Systems

Synopsis

• Examining mechanisms identified in preclinical investigations to enhance myeloid cells and promote antigen presentation to bridge the innate and adaptive immune systems

• Discussing how the SIRPa-CD47 axis stimulates Macrophages to recruit the adaptive immune arm via chemoattraction, and inhibition of this pathway may avoid T cell exclusion

• Sharing preclinical workflows to identify and validate CLEC1 as a novel checkpoint to regulate the antigen cross-presentation properties of dendritic cells

• Discussing early signs of clinical efficacy, identifying differentiated myeloid immune checkpoints, and discussing the importance of combination approaches for myeloid-directed therapies

10:30 am Panel Discussion: Discussing Future Directions in Myeloid-Directed Therapy Development

  • Judith Varner Professor of Pathology, University of California San Diego
  • Nagy Habib Founder & Head of R&D, MiNa Therapeutics

Synopsis

• Acknowledging the limitations of current therapies and the role of the myeloid compartment

• Examining roadblocks to development of myeloid-directed therapy to-date

• Charting future developments in myeloid therapies and discussing the emerging treatment landscape for myeloid therapies

• Considering where will the greatest therapeutic benefit of myeloid-directed therapy be realized

11:00 am Morning Refreshments & Networking

Charting Clinical Progress with Myeloid-Targeted Therapies

11:30 am Sharing Clinical Findings from Modulating Myeloid Cells at Their Inception with Small Activating RNA Therapies to Enhance Anti-Tumor Activity

  • Nagy Habib Founder & Head of R&D, MiNa Therapeutics

Synopsis

• Describing the mode of action of saRNA therapies targeting naïve myeloid cells

• Developing a preclinical package for next-generation myeloid-targeted therapies and translating them into the clinic

• Outlining how indications and patient populations were chosen, and how to best utilize tumor biomarkers as an indicator mechanism

• Sharing patient outcomes, toxicology studies, and dose escalation rationale

12:00 pm Discussing Efficacy & Safety Data for CD47-Targeting Therapy

Synopsis

• Sharing patient outcomes, toxicology studies, and dose escalation rationale

• Considering the safety concerns of a ubiquitously expressed target such as CD47, and the toxicity seen in the clinic

• Translating CD47 therapies to show targeting and validation of targets

12:30 pm Reprogramming TREM1+ Myeloid Cells to Overcome Immunotherapy Resistance in Solid Tumors

Synopsis

• Exemplifying how depletion of different myeloid cell subsets can affect different features of the tumor microenvironment, modulate effector cell activity, and promote tumorigenesis

• Discussing the tolerability of different targets

• Drawing up next steps in clinical development for myeloid-targeting therapies

1:00 pm Learning from CD40 Candidates in Phase II to Inform Back-Translation and Optimize Novel Dendritic & Macrophage-Targeting Therapy

Synopsis

• Sharing clinical learnings from CD40-targeting antibody therapy in pancreatic cancer

• Discussing the design and outline of studies to address dendritic cells and macrophages

• Translating clinical learnings to preclinical CD40 bispecific therapy to drive stronger dendritic cell activation and cross presentation

1:30 pm Lunch & Networking

Devising Biomarker Strategy to Identify Indications, Patient Populations, & Cell Sub-Populations for Therapy

2:30 pm Re-Engineering Myeloid-Mechanical Interactions in the Tumor Microenvironment to Improve Therapeutic Outcomes

  • Meenal Datta Assistant Professor, Aerospace & Mechanical Engineering, University of Notre Dame

Synopsis

• Leveraging RNAseq and single cell omics to identify relationships between mechanical forces in the microenvironment and cellular function

• Characterizing biophysical dynamics of the microenvironment and the impact on disease progression in glioblastoma

• Sharing proof-of-concept with a repurposed FDA-approved drug to modulate myeloid mechanics

• Discussing next steps in in identifying novel therapeutic targets and developing biophysics-based myeloid therapies

3:00 pm Creating a Blockade of Myeloid Immune Checkpoints to Convert Radiotherapy into an Effective, Systemic Immunotherapy

  • Michael Curran Associate Professor, Dept. of Immunology & Co-Founder, ORBIT Platform, MD Anderson Cancer Center

Synopsis

• Discussing how radiotherapy triggers myeloid immune checkpoints that prevent tumor antigen cross-presentation

• Demonstrating that blockade of these “don’t eat me signals” dramatically alters myeloid composition, phenotype, and T cell immune priming post-radiotherapy

• Illustrating the mechanisms by which myeloid checkpoint blockade translates into systemic anti-tumor T cell responses that mediate regression of abscopal tumor sites

3:30 pm Afternoon Networking & Refreshments

Exploring Myeloid Cell Plasticity & Strategies to Harness Repolarization via Therapeutic Targeting

4:00 pm Presentation Contents to be Revealed

4:30 pm Deploying Single Cell Analysis to Inform Mechanisms of Action of Myeloid-Targeted Therapies

  • Xin Yu Director, Oncology Discovery, Merck

Synopsis

• Understanding macrophage and dendritic cell expression profiles from single cell RNA-seq analyses

• Discussing which markers correlate to specific cell function, to comprehend functional relevance and high-impact subsets for targeting

• Uncovering the mechanisms underlying myeloid-targeted therapies undergoing clinical testing

• Discovering markers and novel targets to modulate pro-tumor phenotypes based on mechanistic understanding of differentiation

5:00 pm Finding Novel Targets to Harness Myeloid Repolarization, Demonstrating Functional Change & Anti-Tumor Activity in Preclinical Development

Synopsis

• Defining the term ‘repolarization’ in the context of myeloid cells: recruiting new macrophages vs. changes in tumor-resident macrophages

• Maintaining myeloid cells ex vivo and characterizing the function of M1 vs. M2 phenotypes to determine anti-tumor effects

• Leveraging functional information to identify and validate myeloid targets for clinical development

5:45 pm Chair’s Closing Remarks

6:00 pm Close of Summit