9.00am - 5.00pm EST | 6.00am - 2.00pm PST
9:00 am Registration and Virtual Coffee
9:20 am Chair’s Opening Remark
9:30 am Application of CRISPR/Cas9 In Human iPSC Macrophages For Drug Discovery
Synopsis
- Macrophages play a critical role in immunity. By targeting macrophages our aim is to find genes that play a key role in the context of inflammatory diseases and tumour microenvironment
- iPSCs represent a powerful and robust model to be used in early drug discovery for target identification and validation
- We have built a robust pipeline to perform multiparametric arrayed CRISPR screens in human iPSC derived macrophages under different stimulations
10:00 am Macrophage Phenoconversion and Novel Approaches in Modulating Innate Immune Signaling
Synopsis
- Transcriptional and epigenetic networks control macrophage phenoconversion
- Novel modalities enable modulation of macrophage phenotypes
10:30 am Industry Leader’s Fireside Chat
Synopsis
- An executive panel discussion from the C-level leaders of the field to set the scene on macrophage directed therapy development. Ask your questions live to understand the expert’s thoughts on key topics including safety and toxicity management, controlling the plasticity of macrophages and exploring the immunological memory of macrophages
11:00am Morning Refreshments & Speed Networking
Synopsis
Reinventing the face-to-face networking in the virtual world. We will pair you up with fellow attendees to break the ice and make new and lasting connections!
Discovery & Pre-Clinical Development
Reducing the Recruitment/Presence of Tumor Associated Macrophages for Cancer Immunotherapy
12:00 pm QPCTL is a Small Molecule Drug Target Modulating the Innate Imune Response
Synopsis
- Discovery and validation of QPCTL as a drug target;
- Drug discovery and development efforts at Scenic Biotech
12:30 pm Applying Cell-based Assays to Evaluate the Complex Biology for Drug Candidates Targeting Macrophage-directed Therapies
Synopsis
- Measuring the antibody-dependent cellular phagocytosis (ADCP)
- Distinguishing the mechanisms of action between Fcactive or Fc-inactive CD47 antibodies
- Evaluating CD47/SIRPa targeting therapy as monotherapy or combination therapy with antibodies of ADCP MoA
Clinical Development
Realizing the Clinical Potential of CAR Technology for Next Generation Cell Therapies
12:00 pm Development of CT-0508, a First-in-Class CAR-M, For Solid Tumor Immunotherapy
Synopsis
- Key rationale for development of monocyte/ macrophage based therapeutics
- Overview of Carisma’s proprietary engineered mono/macrophage cell therapy technology
- CT-0508: clinical trial in progress update
12:30 pm Harnessing Myeloid Cells To Kill Cancer & Alter The TME
Synopsis
- The functional potential of myeloid cells is unparalleled in the immune system
- The ATAK myeloid cell platform arms myeloid cells with chimeric antigen receptors with specificity for proteins expressed on tumor cells
- Innate receptors allow for potent myeloid cell activation after engagement with tumor antigens
1:00 pm Lunch & Networking
Identifying Novel Macrophage Targets for Anti-Tumor Immunity
2:00 pm CLEC-1 : Novel Don’t Eat Me signal Regulating Anti-Tumor Responses
Synopsis
- CLEC-1 inhibits dendritic cells antigen cross-presentation and macrophage phagocytosis in synergy with tumortargeting mAb
- Cell stress/death induced by radiation or chemotherapy increased CLEC-1 ligand expression
- Increased anti-tumor responses in vivo in CLEC-1 KO mice and synergy with chemotherapy
2:30 pm Targeting a Novel Target on Tumor Associated Macrophages In Triple Negative Breast Cancer – Opportunity For A First-In-Class Therapeutic
Synopsis
- Genagon has characterized a novel target within immuno-oncology specialized for cancers with a high infiltration of macrophages.
- The target accumulates on the surface of cells within the tumor, enabling treatment with low risk of side-effects
- Genagon is targeting novel biology with an opportunity for a first- in-class therapeutic in the $500 million market triple negative breast cancer.
3:00 pm Pro-Tumourigenic Polarisation Of Human Macrophages By Low Ph Is Fully Reversed By Small Molecule Inhibitors Of GPR65: Implications For Immunotherapy
Synopsis
- Tumour-associated macrophages are typically protumourigenic, exhibiting a Th2 activation signature and supporting angiogenesis and tissue growth
- The adoption of this phenotype in the tumour can be fully explained by the impact of low ph on macrophage gene expression acting via the pH-dependent GPCR, GPR65
- This polarisation can thus be fully reversed by novel, small molecule GPR65 inhibitors with far-reaching consequences for immunotherapy
Exploring Clinical Trial Case Studies for CD47/SIRPα Targeted Macrophage Therapies
2:00 pm DSP107, a First-in-Class CD47x41BB Targeting Fusion Protein, Activates Both – Innate and Adaptive Immunity
Synopsis
- Second generation CD47 targeting compound with a best in class profile
- Unique mechanism of action – activates both the innate and the adaptive immune systems
- Excellent safety profile without hematological toxicities
2:30 pm Combinations with CD47-SIR Blocker for Enhanced Efficacy
Synopsis
- Evaluating the clinical potential of utilizing a next generation CD47 blocker with rational combinations
- Showing clinical efficacy in patients with advanced lymphoma patients
3:00 pm Panel Discussion: Exploring How Best to Harness the Anti-Tumor Potential of Macrophages
Synopsis
- Discussing the resistance mechanisms against myeloid cell recruitment inhibition and lack of effect on tissueresident TAM populations
- Considering the risk of accelerated metastasis following withdrawal of CCL2/CCR2 inhibitors
- Do we need to look to alternative targets to overcome these limitations?
3:30 pm Afternoon Break & Poster session
Identifying Novel Macrophage Targets for Anti-Tumor Immunity
4:00 pm Using the Human Immune System to Identify Antibodies That Modulate the Tumor Microenvironment
Synopsis
- Discovery of lead antibody OR2805 from a cancer elite responder that relieves the suppressive effects of M2 macrophages on T-cell function
- Demonstrates anti-tumor activity in cancer xenograft models
4:30 pm Reprogramming Human Macrophages to Achieve Anti-Tumor Immune Response.
Synopsis
- Macrophages adopt functional roles in response to signals from their environment. Tumor-associated macrophages (TAMs) are regulators of interactions between immune system and cancer, they fuel tumor progression, but impact responses to therapy.
- We found novel targets that change macrophages into anti-tumor response enablers and validated targets modulating human macrophage biology.
- Verseau lead programs reprogram macrophages to a pro-inflammatory state, activates T cells, and attracts immune cells to generate anti-tumor responses.
Exploring Clinical Trial Case Studies for CD47/SIRPα Targeted Macrophage Therapies
4:00 pm Preclinical Development Of A Bi- Functional Sirpa-Fc-CD40L (SL-172154) Fusion Protein Demonstrates Translatable On-Target Pharmacodynamic Activity; And Is Now Being Evaluated In Multiple Human Clinical Trials
Synopsis
- SL-172154, a bi-functional SIRPa-Fc-CD40L fusion protein, can bridge innate and adaptive anti-tumor immunity
- SIRPa-Fc-CD40L provides simultaneous CD47 checkpoint blockade and antigen presenting cell costimulation via CD40/L; thereby inducing a robust antigen-specific CD8+ T cell anti-tumor response
- SL-172154 is currently being clinically evaluated in ovarian cancer and head and neck or skin squamous cell carcinoma
4:30 pm TTI-622 and TTI-621 Target the CD47 “Don’t Eat Me” Signal on Tumor Cells
Synopsis
- TTI-622 and TTI-621 are soluble SIRPαFc decoy receptors that neutralize the suppressive effects of CD47 and deliver an activating signal to macrophages through Fc receptors.
- TTI-622 and TTI-621 are differentiated from other CD47 blocking agents by the lack of RBC binding and greater monotherapy activity.
- Emerging clinical data for both agents will be discussed