8:25 am Chair’s Opening Remarks

Leveraging Clinical Validation to Turbocharge Macrophage-directed Therapy Development

8:30 am Rational Combinations with Magrolimab in Hematologic Malignancies

  • Carol O’Hear Vice President, Clinical Development, Hematology Franchise Head, Gilead Sciences

Synopsis

• Demonstrating robust preclinical programs to create a rational therapeutic design and combination strategy
• Clinical efficacy of magrolimab in hematologic malignancies
• Share safety considerations of targeting CD47 and the toxicity profile seen in the clinic

9:00 am PY314: Targeting Trem2 Positive Macrophages in Patients with Advanced Solid Tumors

  • Leonard Reyno Executive Vice President & Chief Medical Officer, Pionyr Immunotherapeutics

Synopsis

• TREM2 is highly expressed on immune-suppressive TAMs within the TME, where it functions as a negative regulator of inflammatory responses
• Pionyr’s humanized IgG1 afucosylated monoclonal antibody (PY314) specifically binds human TREM2 and balances the TME (‘Myeloid Tuning’) by specifically depleting TREM2+ TAMs, via antibody-dependent cell-mediated cytotoxicity (ADCC) and/or antibody-dependent cellular phagocytosis (ADCP)
• Preclinical and clinical results from a first in human trial of PY314 alone and in combination with pembrolizumab

9:30 am Clinical Update on Bexmarilimab – the First-in-Class Anti-CLEVER-1 mAb

Synopsis

• FiH Phase I/II study showing extended survival in last line patients
• Review biomarkers to identify responding patients
• Outline future development plans based on the FiH Phase I/II results

10:00 am Measurement of Toll-Like Receptor Activation with a Bioluminescent TLR Reporter Bioassay

Synopsis

  • Modulation of TLRs can tune myeloid cell phenotype and immune responses
  • TLR Bioassay Cells respond to agonists of TLR 1, 2, 4, 5, 6, 7 and 8
  • The Bioassay is easy-to-use, robust, and pre-qualified according to ICH

10:30 am
Morning Refreshment Break & Speed Networking

Preclinical & Discovery

Overcoming Challenges with Current Models to Supercharge Preclinical Results

11:30 am Integrated New Macrophage Target Discovery and Validation Engine

Synopsis

• Identifying the areas where current models do not allow for streamlined identification and validation of new macrophage targets
• Introduction to Macomics’ integrated new macrophage target discovery and validation engine.
• Future perspectives

12:00 pm Addressing Human Myeloid Compartment in a Preclinical Mouse Model Featuring Human Immune System

  • Kader Thiam Senior Vice President, Discovery - Preclinical Models & Services, GenoWay

Synopsis

  • Outlining BRGSF-HIS mice: Immunodeficient mice displaying functional human lymphoid and myeloid compartments, without GvHD and side effects 
  • Examining myeloid cells functionality and assessing immune modulation induced by biologics in BRGSF-HIS model 
  • Showcase of assessment of immune targeting agents in immune checkpoint humanized models 

Clinical & Discovery

Incorporating an Effective Dosing Strategy to Guarantee Smooth Clinical Development

11:30 am Evorpacept: a Phase 2 CD47 Blocker Uniquely Designed for Use in Combination Therapies to Safely Maximize Anti-Cancer Activity

  • Jaume Pons President & Chief Executive Officer, ALX Oncology

Synopsis

• ALX Oncology’s lead product candidate, evorpacept, is a next-generation CD47 blocking therapeutic that combines a high-affinity CD47 binding domain with an inactivated, proprietary Fc domain
• Evorpacept has demonstrated promising clinical responses and tolerability across a range of hematologic and solid malignancies in combination with targeted antibodies, pembrolizumab, and chemotherapy
• ALX is currently enrolling subjects in multiple randomized, phase 2 studies of evorpacept in solid tumors and hematological malignancies

12:00 pm Determining Safe Dosing to Prevent Off-Target Toxicity

Synopsis

• Identifying whether the response is dose-dependent to avoid excessive drug application
• Examining preclinical data and pharmacodynamic activity to determine drug dosage and frequency whilst ensuring therapeutic safety
• Utilizing a priming dose for preliminary infusion to lower the initial toxicity of therapeutic
• Assessing possible areas for toxicity to occur beyond hematologic toxicity

12:30 pm
Lunch Break & Networking

Exploring Macrophage-directed Therapy Approaches Beyond CD47 Targeting

1:30 pm Small Molecule GPR65 Inhibitors Reverse Acidosis-Induced Immunosuppression in Macrophages and Suppresses Tumor Growth in vivo Via an Elevation of Natural Killer (NK) Cells

Synopsis

  • Solid tumors are typically more acidic than surrounding normal tissue 
  • This acidity activates GPR65 on macrophages, causing a suppression pro-inflammatory cytokines and chemokines  
  • Small molecule GPR65 inhibitors counteract this effect and reduce tumor growth in vivo through an increase in the infiltration of key effector cells 

2:00 pm A Novel Approach to Cancer-Agnostic Treatment of Tumors With Non-Genetically Modified Macrophages

  • Rita Barcia Vice President, Process Development & Operations, SIRPant Immunotherapeutics

Synopsis

  • SIRpant uses a non-genetic approach to reprogramming macrophages that removes SIRPɑ and simultaneously reprograms them to promote an anti-cancer response whilst reducing manufacturing time 
  • Our macrophages act by directly attacking cancerous cells, stimulating cancer neoantigen-specific cytotoxic T cells and antibodies, reducing immunosuppressive elements, and perpetuating a pro-inflammatory TME that favors cancer elimination 
  • Overcoming manufacturing challenges in the difficult transition from bench to clinic and setting up a Phase 1 study 

Assessing CD47 Targeted Therapy Clinical Advances

1:30 pm DSP107, a Novel CD47x4-1BB targeting agent

Synopsis

Virtual Presentation

  • Improving Target Specificity and Activity Through the Use of Bispecific Fusion Protein
  • Designing bispecific agent to successfully mediate dual activation of innate and adaptive immune systems
  • Transforming safety profile and avoiding hematological toxicities
  • Enhancing the potential for the treatment of solid and hematological malignancies 

Track Closed

2:30 pm
Afternoon Refreshments and Poster Session

Exploring Novel Targets to Mediate Macrophage-directed Targeting

3:15 pm ISB 1442, a First-in-Class CD38 and CD47 Bispecific Antibody Innate Cell Modulator for the Treatment of CD38 Positive Hematologic Malignancies

Synopsis

  • ISB 1442 represents a novel approach for the treatment of CD38+ tumors by cotargeting CD38 and CD47 with a 2+1 biparatopic bispecific antibody format with Fc engineering enhancing Fc effector functions
  • ISB 1442 shows higher potency relative to daratumumab in CD38high/low tumor models as measured by multiple antibody-dependent mechanisms of action in vitro and in vivo
  • ISB 1442 shows low on-target off-tumor binding and no RBC depletion compared to anti-CD47 mAb (5F9), potentially resulting in a better therapeutic index than anti-CD47 mAbs

3:45 pm Targeting Immunosuppressive MARCO+ Myeloid Cells to Unleash Anti-Tumor Immunity

Synopsis

  • Pionyr identified the Macrophage Receptor with a Collagenous Structure (MARCO) as a potential myeloid reprogramming target and developing a humanized  anti-MARCO monoclonal antibody (mAb), termed PY265
  • PY265 induced reprogramming of M2-like macrophages and immunosuppressive mMDSCs to M1-like  macrophages and pro-inflammatory monocytes, leading  to pro-inflammatory immune activation
  • PY265m, a surrogate antibody specific to mouse MARCO, demonstrated significant anti-tumor activity both as a single agent in CPI-sensitive syngeneic tumor models and in combination with anti-PD-1 in CPIresistant syngeneic tumor models 

4:15 pm The C-type Lectin CLEC-1 is a Sensor of Cell Death Limiting Myeloid

Synopsis

  • CLEC1 recognizes a ligand expressed by cells undergoing necrosis
  • CLEC1 regulates the function of macrophages and cDC1
  • CLEC1 inhibition unleashes anti-tumor responses

4:45 pm Developing a Therapy to Target a Novel Macrophage Checkpoint

  • Amira Barkal Co-Founder & Chief Executive Officer, Pheast Therapeutics

Synopsis

  • Blocking CD24 signalling which is highly expressed on many tumors
  • Targeting this ‘don’t eat me’ signal to mediate macrophage phagocytosis

5:15 pm Close of Conference Day One