8:00 am Morning Coffee

OPTIMIZING CLINICAL TRIAL DESIGN FOR INNATE IMMUNOTHERAPY DRUG DEVELOPMENT

8:50 am Chair’s Opening Remarks

9:00 am Breakfast Panel: Dissecting the Recent Clinical Trial Failures & Experience Gained

  • Lei Jin Assistant Professor - Medicine , University of Florida
  • Diwakar Davar Assistant Professor - Phase, Therapeutics & Melanoma , University of Pittsburgh
  • Kate Fitzgerald Professor - Program in Innate Immunity, Division of Infectious Diseases & Immunology , UMass Medical School
  • Thomas W. Dubensky President, Tempest Therapeutics

Synopsis

  • Understanding the challenges and how these can be overcome in future
  • Discussing target engagement and response biomarkers
  • Exploring similarities between trial design in preclinical vs clinical settings
  • Debating the reliability of current biomarkers
  • Understanding the design, translation and execution in response assessments
  • Determining “how much PRR activation, is too much” in patients given that most if not all innate agonists have a bell-shaped dose response curve
  • How do we identify a phase 2 recommended dose in patients (maximum tolerated dose, mean fold-change in cytokine responses, avoiding immune suppressive cytokine induction)

9:30 am Consistency in Global Clinical Trials: The Impact of Common Human HAQ-STING in Health & Medicine

  • Lei Jin Assistant Professor - Medicine , University of Florida

Synopsis

  • Understand how the human STING gene is highly heterogeneous with significant population stratification
  • Explore how common human HAQ-STING replaced AQ-STING in non-Africans indicating a natural selection for HAQ-STING during the out-of-African migration
  • Delve into how HAQ and AQ STING regulates fatty acid metabolism independent of type I IFNs

10:00 am Optimizing Patient Selection & Standardizing the Dose, Scheduling & Response Analysis; Targeting TLR9 in High-Risk Resectable Melanoma & Neoadjuvant CMP-001 & Nivolumab

  • Diwakar Davar Assistant Professor - Phase, Therapeutics & Melanoma , University of Pittsburgh

Synopsis

  • Assessing the use of historical markers and the need for further exploration
  • Understanding the design, translation and execution in response assessments

10:30 am Morning Refreshments & Poster Session

OPTIMIZING YOUR PRR-BASED DRUG DELIVERY TECHNOLOGY

11:30 am Intratumoral Immunotherapies Currently Undergoing Development & Updated on Efficacy Data

Synopsis

  • Review of all intratumoral immunotherapies that have been approved or have shared efficacy and safety results from clinical development
  • Challenges for intratumoral immunotherapy development, best endpoint to target
  • Predictive biomarkers; how and when assess them

12:00 pm Eradication of Established Tumors with Induction of Innate & Adaptive Immunological Memory in Multiple Preclinical Models with Systemically Administered Decoy Bacteria, a Multi-TLR Agonist Therapeutic Vaccine

Synopsis

  • Explore how attenuated and killed, non-pathogenic, Gram-negative (Decoy) bacteria can induce potent priming of innate and adaptive anti-tumor immunity
  • See how Decoy bacteria can produce single agent activity and safe tumoreradicating synergy with each of several different classes of immuno-oncology agents
  • Decoy bacteria can also produce safe, single agent activity against chronic viral infections, including HBV, in preclinical models

ANALYSING & OPTIMIZING THE VARIOUS DRUG FORMAT OPTIONS

12:30 pm Lunch Break

1:30 pm Site-Specific TLR7 Agonist Antibody-Drug Conjugates as Next Generation ADCs

Synopsis

  • Presenting on the site-specific TLR7a ADC developed by EuCODE platform with an expanded genetic code
  • Reviewing how protein medicinal chemistry enables fine-tuning of TLR7a ADC to balance potency and safety in preclinical studies
  • Demonstrating how Ambrx’s TLR7a ADCs elicit strong anti-tumor responses as single-agent as well as in combination therapies

2:00 pm Case Study: Initiating an Innate Immune Response with Oncolytic Virotherapy

Synopsis

  • Assessing the interactions important to PRR & OV: the innate-adaptive immune axis
  • Discussing concept, design, development, validation and more

2:30 pm Panel Discussion: What is the Best Modality & Delivery Approach to PRR-Pathway Targeting?

  • Adi Diab Associate Professor - Melanoma Medical Oncology , MD Anderson Cancer Center
  • Andrew Miller Co-founder & Vice President - Immunology & Operations , Apros Therapeutics
  • Michael J. Newman Founder & Chief Scientific Officer , Indaptus Therapeutics
  • Mingchao Kang Group Lead, Head Technology Platform , Ambrx

Synopsis

  • Discussing safety profiles, dosing and scheduling considerations, therapeutic window
  • Dissecting drug design approach for systemic and intratumoral
  • Understanding possible regulatory considerations
  • Mechanisms of action that are leading to strong efficacy
  • Enhancing administration and delivery of therapies for safe and effective clinical outcomes
  • Systemic delivery technologies vs intra-tumoral delivery technologies

3:00 pm Afternoon Refreshments

NEXT STEPS IN PRR COMBINATION INTERVENTIONS TO HEIGHTEN DRUG EFFECT & OVERCOME RESISTANCE – THE FUTURE?

3:30 pm Navigating & Assessing Combination with Checkpoint Inhibitors & Other Options

  • Diwakar Davar Assistant Professor - Phase, Therapeutics & Melanoma , University of Pittsburgh

Synopsis

  • Innate immune stimulating therapies and their contribution to T-cell-based immunotherapies
  • Orchestrating T-cell recruitment and infiltration at the tumor site by targeting the myeloid lineage component of the innate immune system
  • Establishing strategic partnerships with PD-(L)1 developers
  • Combinations with non-approved anti-PD-(L)1 inhibitors
  • Examining the other options
  • Understanding the pathway interactions and scientific rationale
  • TIGIT/TIM-3/LAG3

4:00 pm STING Modulators as Therapeutic Agents for Infection, Auto-Immune & Oncology Indications

  • Joshi Ramanjulu Senior Director & Head of Project Leader Group, Innate Immunity Research Unit & Senior Fellow , GlaxoSmithKline

4:30 pm Closing Panel Discussion: Thoughts & Future Directions for PRR

  • Kate Fitzgerald Professor - Program in Innate Immunity, Division of Infectious Diseases & Immunology , UMass Medical School
  • Babette Schade Head of Biology Lab & Principal Scientist , TargImmune Therapeutics
  • Matt Booty Lead Scientist , Spring Discovery
  • Brian Horsburgh Chief Executive Officer, Activate Therapeutics

Synopsis

  • Thoughts and rationalizing on potential best outcomes combos
  • Reviewing the various combination approaches and new targets coming in – thought experiment based on pathway
  • What are the combinations and new targets that are going to push the field forward in a durable and effective way?
  • Designing for approval in monotherapy vs combination therapy
  • Advice on how to take novel targets into the clinic?
  • Case studies from Triple Negative Breast Cancer, Pancreatic Cancer and Non-Small Cell Lung Cancer
  • Developing treatments for patients with advanced metastatic disease or malignancies refractory to initial treatment
  • Significance and Role of Pattern recognition receptors in malignancy – a promising novel approach for cancer immunotherapy?
  • Autoimmune indications and MoA rationale
  • Dissecting single agent tolerability vs combination differences
  • Understanding resistance and biological cause for appropriate combination rationale: clinical feasibility with patients in mind
  • What are we learning from the clinic?
  • Beyond oncology – autoimmune

5:00 pm Chair’s Closing Remarks & Close of Summit