Exploring Means to Minimize Toxicity of Cell Engagers to Ensure Patient Safety

8:25 am Chair’s Opening Remarks

8:30 am Reducing Key Toxicities with T Cell Engaging Bispecifics

Synopsis

• What are the key toxicities that are common with T cell engagers?
• Exploring strategies Pfizer has used to detect and minimize potential toxicities, with a focus on solid tumor indications
• Examining how to reduce CRS with different approaches, including pharmacological blockade of cytokines

9:00 am A New Concept for Cancer Immunotherapies with Robust Efficacy and Minimal Toxicity

Synopsis

  • Elstar’s molecules are built to target tumors through binding simultaneously two cell surface antigens allowing precision delivery of one or more of our immune engager modules.
  • Our non-CD3 T cell engager drives expansion and activation of a discrete T cell population without generating cytokines responsible for CRS
  • We also have developed a new generation of immunocytokine with radically different pharmacology allowing both enhanced tumor targeting and reduced systemic toxicity

9:30 am A Novel Multispecific T Cell Engager Platform for a Better Therapeutic Window

Synopsis

• TeneoBio’s sequence-based discovery: Profiling the B-cell repertoire of human Ig transgenic rats for diverse leads against target antigens of interest
• Identifying and optimizing multi-specific leads for a novel CD3-based T-cell engager platform
• Mitigating safety risk with T-cell engagers that maximize target cancer cytotoxicity and minimize cytokine release
• Improving the therapeutic window of T-cell engagers for combination therapies

10:00 am Prevention and Treatment of CRS with Bispecific Antibodies

  • Anthony Stein Clinical Professor, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope

Synopsis

• Prevention –Dose step, Medication
• Treatment – Steroids, Tocilizumab
• Grading System

10:30 am Morning Refreshments & Networking

11:00 am Maximizing Therapeutic Potential by Affinity and Avidity Engineering

  • Seung Chu Associate Director - Cell Biology, Xencor

Synopsis

• Antigen affinity optimization for increased exposure and reduced toxicity
• Multi-valent antibody scaffold for avidity-mediated tumor selectivity

Assessing the Limitations of Cell Engagers in Solid Tumor Indications

11:30 am COBRA™: A Novel Conditionally Active T-cell Engager Platform

  • Chad May Senior Vice President - Research & Development, Maverick Therapeutics

Synopsis

• Solid tumor directed T-cell engaging bispecifics are limited by target expression on normal tissues
• COBRA™ platform is designed to reduce toxicity by restricting T cell engagement to within the tumor microenvironment
• Review the pros and cons of solid tumor xenograft models to measure efficacy
• Demonstrate potent COBRA™ mediated tumor regressions

12:00 pm Rational Combinations for Bispecific T-cell Engager (BiTE®) Immune Therapy in Solid Tumors

12:30 pm Utility of the ADAPTIR™ Platform to Engage and Modulate Immune Cells for the Treatment of Cancer and Autoimmune/Inflammatory Diseases

Synopsis

• Overview of the ADAPTIR™ platform and screening methodology to identify active, manufacturable bispecific proteins
• APVO436, an anti-CD3 T-cell engager with unique characteristics for the treatment of AML
• ALG.APV-527, an anti-41BB x 5T4 bispecific that engages T cells for the treatment of solid tumors

1:00 pm Exploring Databases for Preclinical and Clinical Developments of T Cell Engagers

  • Andy Cook Director of Digital Products, Beacon Targeted Therapies

Synopsis

  • Comprehensive analysis of all cell therapy and antibody-based t-cell engagers in
    clinical and preclinical development
  • Target distribution and trends
  • Pipeline conversion analysis

1:15 pm Lunch & Networking

2:15 pm Panel Discussion: Focusing on Dosing Regimens and the Therapeutic Window in order to Develop Easily Administered Drugs

Synopsis

• Exploring the potential ability of drugs with short serum half-lives allowing precise control of drug levels within the patient to enhance their potential safety
• Determining the exposure levels needed for cell engagers to be effective
• Understanding the importance of dose selection and escalation
• What preclinical information is actually useful?
• Do we really need to start at the MABEL dose or could we start higher for terminal indications?

3:15 pm Afternoon Refreshments

Developing Strategies to Ensure Scalability of Cell Engagers

3:45 pm Exploring Formats and Binding Valency in Developing Manufacturable Immune-Redirecting Bispecifics

  • David Poon VP, Business Development and Alliance Management, Zymeworks

Synopsis

• Overview of the best-in-class Azymetric™ platform for generating bispecifics
• Highlighting engineering strategies to improve manufacturability
• Optimizing activity of immune-engaging bispecifics and correlations with formats and binding valency

4:15 pm The Promise of Next Generation T Cell Engagers for Cancer Treatment

Synopsis

• Bispecific T cell engagers are able to bring T cells proximity to cancer cells for tumor killing
• By bringing in additional immune modulatory specificity to address tumor immune-escaping mechanisms and to overcome immunosuppressive tumor microenvironment, next generation multi-specific T cell engagers may hold great promise to rival CAR-T therapies with several potential advantages

4:15 pm Clinical and Translational Experience from a Phase I Clinical Study of Flotetuzumab, a CD123 x CD3 DART® Molecule, in Acute Myeloid Leukemia

  • Paul Moore VP, Cell Biology and Immunology , MacroGenics

Synopsis

  • Flotetuzumab is designed to target T cells to kill CD123-expressing tumor cells
    present in acute myeloid leukemia (AML) and other hematologic malignancies
  • In Phase I studies, flotetuzumab elicits anti-leukemic activity in relapse/refractory
    (R/R) AML patients with a dosing strategy optimized to potentially ameliorate
    cytokine release syndrome (CRS)
  • Translational studies also demonstrate the emergence of an exhaustion
    T-cell phenotype in non-responders and support the rationale for combining
    flotetuzumab with checkpoint blockade (i.e.: anti-PD-1)

4:45 pm Chair’s Closing Remarks

4:50 pm Close of Conference