Conference Day Two

8:55 am Chair’s Opening Remarks

Discovering the Latest Preclinical & In-Human Advancements in Inflammasome Targeting to Transfer Key Learnings & Confidently Move Towards the Clinic

9:00 am NLRP3 Inhibitor to Treat Neuroinflammatory & Neurodegenerative Diseases: From Discovery to Development

  • Anick Auger Senior Director, Head of Pharmacology, Ventus Therapeutics

Synopsis

Session Overview to Be Confirmed

9:30 am Exploring the Development of RRx-001: the NLRP3 Small Molecule Inhibitor for a Variety of Inflammatory Diseases

  • Tony Reid Chief Executive Officer, EpicentRx

Synopsis

  • Understanding the mechanism of action and preclinical data for the therapeutic candidate
  • Highlighting key formulation and delivery considerations to be on-target and measuring off-target effects
  • Identifying the next steps for the therapeutic candidate

Humanized Mouse Models & Innovative Preclinical Models for Inflammasome Therapeutic Translational Success

10:00 am Novel Potent, Selective, & Brain Penetrant NLRP3 Inhibitors Mitigate Neuroinflammation in Preclinical Models

  • Davide Basco Team Leader - Neuroinflammation, AC Immune SA

Synopsis

  • Highlighting the potent NLRP3 inflammasome inhibitor
  • Showcasing optimization of brain exposure
  • Demonstrating efficacy in mouse models of human disease and target engagement in the central nervous system

10:30 am Morning Break & Networking

11:00 am Discovery of Novel & Potent Inhibitors Targeting the NLRP3 Pathway

Synopsis

  • Using the physic-based computational platform, allied with machine learning techniques to enable the identification of NLRP3 inhibitors
  • Highlighting the inhibitor’s capability to target both peripheral and CNS diseases
  • Harnessing a range of functional and mechanistic cellular assays, in vivo pharmacodynamic and disease models to explore pathway inhibition

11:30 am Anti-ASC Antibodies: A Promising Approach for Dual Targeting of Protein Aggregation & Inflammation

Synopsis

  • Development and characterization of monoclonal antibodies targeting ASC
  • In vitro efficacy in protein aggregation and inflammation assay
  • In vivo target engagement and efficacy in a model of Amyloidosis

Getting to the Target: Formulation & Delivery Considerations for Inflammatory Diseases

12:00 pm Specifically Targeting & Avoiding Off-Target Effects: Identification of Novel, Highly Potent, CNS Penetrant NLRP3-Specific Inhibitors

Synopsis

  • Revealing NLRP3 levels rise with age and are positively correlated with all-cause mortality and cognitive decline
  • Functionally inhibiting NLRP3 inflammasome in vivo and in vitro with comparable or superior potency relative to publicly known inhibitors
  • Identifying molecules that allow favorable oral bio-availability and blood-brain barrier penetration

12:30 pm Lunch & Networking

Deciphering the Upstream Activation Mechanisms of Inflammasomes to Understand Regulatory Factors of Inflammation for Therapeutic Targeting

1:30 pm Targeting Inflammasomes Through Other Mechanisms: The Role of Innate Immune Sensors in the Regulation of Inflammasomes

Synopsis

  • Regulating Inflammasome activation via P2X7 and adenylate cyclase
  • Exploring GPCR19 agonism inhibits both the priming phase and the activation phase of the inflammasome
  • Highlighting the promising therapeutic approach for inflammatory diseases, such as atopy dermatitis, Alzheimer’s disease, and infection disease

Assessing Downstream Targets of the Inflammasome Pathway & Pathway Cross-Talks to Complete the Picture for Effective Targeting

2:00 pm Identifying Cell-Death Pathway & Inflammasome Pathway Cross-Talk As Contributing Drivers to Cell Death

  • Hao Wu Professor, Harvard Medical School

Synopsis

  • Deliberating how useful it is to target pyroptosis and apoptosis in inflammatory diseases

2:30 pm Exploring Inflammasome-Activated Gasdermin Triggering Pyroptosis to Hone Therapeutic Development

Synopsis

  • Discovering novel Gasdermin-D inhibitors
  • Highlighting the functional effect of inhibitors

Focusing Inflammasome Therapeutic Development to Accelerate the Field to the Clinic

3:00 pm Roundtable: From Discovery to Preclinical Development to the Clinic: Addressing the Key Next Steps to Take as A Field to Supercharge Inflammasome Therapeutics to the Patient

Synopsis

  • Discovery & Novel Inhibitors/Activators: Should the focus be on NLRP3? What are the benefits of looking to other targets? What are the upstream and downstream considerations in the pathway?
  • Preclinical Development: Should we look to animal models or focus on the development of novel models? What disease applications should be the go-to?
  • Bridging the Gap: Translational Considerations Where do we go for biomarker development whilst we wait for clinical readouts?
  • Looking to the Clinic Which patient population will inflammasome therapeutics have the greatest benefit? What should be considered for dose and targeting?

3:30 pm Panel Discussion: Assessing the Current Landscape of Inflammasome Therapeutics to Identify the Bottlenecks, Key Field Considerations, & Debating the Future of Inhibitors/Activators

  • Jonathan Kagan Marian R. Neutra, PhD Professor of Pediatrics, Harvard University
  • Anick Auger Senior Director, Head of Pharmacology, Ventus Therapeutics
  • Hao Wu Professor, Harvard Medical School

Synopsis

  • Looking outside of NLRP3: Which inflammasome do we think is going to be the next go-to? And will it be disease-specific?
  • Exploring upstream targets of inflammatory processes:
  • Diving into downstream targets of inflammasome activation to complete the picture:
  • Understanding the key limitations of preclinical models to move forward: Which models do big pharma want to see inflammasome data in?
  • Harnessing novel humanized preclinical models: Which models do we think will be effective and well adopted by the field?
  • Navigating measuring target engagement and patient selection: What should we explore for inflammasome biomarkers?

4:00 pm Chair’s Closing Remarks