7:30 am
Registration & Networking Coffee
8:25 am Chair’s Opening Remarks
Recent Progress & Advancing Assays for Inflammasome Drug Development
8:30 am Targeting IL-1b Pathway for Cancer Immunotherapy
Synopsis
- IL1b blockade was shown to inhibit chronic inflammation and prevent occurrence of lung cancer in a susceptible population
- Single cell RNAseq analysis of primary tumor samples with in vitro treatment highlight cell targets and pathways for MoA
- Mouse tumor models show a shift from immune suppression to activation with IL1b blockade
9:00 am Translational Approaches for the Development of Novel NLRP3 Inhibitors
Synopsis
- Explore ex vivo stimulated blood assays for early clinical evaluation of pharmacodynamics
- Use of the D305N NLRP3 mechanistic mouse model for assessment of in vivo target cover
- Discuss In vivo disease models for PK/PD assessment
9:30 am Panel Discussion: Addressing the Current R&D Bottlenecks & Gaps in Inflammasome Therapeutic Research
Synopsis
- What are the limitations of currently available animal models for recapitulating inflammasome-drug-tissue interactions?
- How/Should we be targeting inflammasomes locally at the sites of inflammation?
- How are we thinking about dosing for a known pharmacological effect/target engagement to specific organs
without systemic exposure/immunosuppression? - How are we thinking about dual/multi- inflammasome inhibition in terms of increasing drug specificity and
limiting multifactorial inflammation in disease?
10:00 am A Suite of Assays to Rapidly Probe Inflammasome Pathway Antagonism in Cells: Focus On Development of Lumit™ IL-18
Synopsis
- Using complementary NLRP3 target engagement and functional inflammasome
assays to interrogate putative NLRP3 inhibitors - Using NLRP3 target engagement and functional Caspase-Glo 1 and Lumit™ IL-1β
assays for screening of inflammasome antagonism - Developing a Lumit™ IL-18 immunoassay
10:30 am
Speed Networking & Morning Coffee Break
Synopsis
This is your opportunity to network and forge new contacts with fellow Inflammasome enthusiasts in a relaxed environment.
Molecular Underpinnings of Inflammasome Dysregulation
11:30 am Human NLRP1: Patients, Mutations & Indications
Synopsis
- Learn how germline GoF NLRP1, or LoF DPP9, mutations activate the inflammasome in humans
- Understand the various DAMPs and PAMPs that can trigger human NLRP1
- Examine to what extent NLRP1 is a validated drug target for orphan and/or common clinical indications
12:00 pm The CARD8 Inflammasome in HIV Pathogenesis & Disease Progression
Synopsis
- Learn how CARD8 is an inflammasome sensor for HIV protease activity
- Discuss how HIV activates the CARD8 inflammasome to trigger pyroptosis of CD4+ T cells
- Understand how inhibition of CARD8 activation prevents HIV-induced CD4 loss and disease progression
12:30 pm Understanding the Intersection Between Autophagy, Pyroptosis, Lysosomal Flux & Inflammasome Activation for Inflammasome Research
Synopsis
- Delving into the science behind oxidative inflammasome and metabolism activation
- Discussing translational takeaways and questions still needing answers
Advances in Proof-of-Concept Trials in Various Diseases
11:30 am RRx-001, a Small Molecule Anticancer Agent in Phase 3, Protects Against Inflammasome-Driven Diseases
Synopsis
- Evaluate strategy and execution of drug design and translational development
- Understanding relevant pathology of disease and most up to date learnings on the inflammasome mechanisms, drug design, and patient population
- Exploring the latest data, potential biomarkers, challenges, and future directions
12:00 pm Harnessing the Power of AI to Decode the GBA: the Inflammasome Connection
Synopsis
- Understand the connection between host inflammasome and gut-brains axis (GBA)
- Discuss Invea Therapeutics proprietary AI/ML platform and approach to discovery and de-risking GBA targets and candidate therapeutic molecules across the continuum of cellular/molecular processes underlying inflammation and its progression, from inflammasome activation to matrix remodeling/fibrosis
- Learn about INVA-8003, a “first in class” small molecule inflammasome inhibitor targeting oligomerization of ASC, a key component in the formation of all canon
12:30 pm Understanding Inflammasome Biomarkers in Brain Injury, Alzheimer’s Disease & COVID-19
Synopsis
- Explore how the inflammasome plays a role in early disease onset in a variety of diseases
- Review how the early role of the inflammasome in disease renders inflammasome signaling proteins as great biomarkers of early disease diagnosis
- Discuss how with the current development of therapies intended to directly inhibit the inflammasome, inflammasome signaling proteins have the potential to be great theranostic biomarkers
1:00 pm
Lunch Break & Poster Session
Synopsis
This is an informal session to help you connect with your peers in a relaxed
atmosphere and continue forging new and beneficial relationships. You will have
the opportunity to present your work, and review presentations displaying novel
approaches and findings.
2:00 pm MAP Kinase Regulation of Inflammasome Licensing and Pyroptosis
Synopsis
- Explore approaches to investigate kinase function
during inflammasome triggering - Learn how distinct MAP3K complexes promote NLRP3
inflammasome formation and pyroptosis - Evaluate potential approaches to regulate IL-1 output in
models of autoinflammatory disease
Progress in Inflammasomes Beyond NLRP3
2:30 pm Gasdermin B as a Therapeutic Target for GI-associated Diseases
Synopsis
- The role of gasdermin B (GSDMB) as an executioner of pyroptosis in intestinal epithelial cells is controversial, with emerging evidence supporting its role in alternative activities that go beyond pyroptotic cell death
- Recent findings regarding GSDMB’s function during gastrointestinal (GI) disorders suggest an overall protective role of epithelial-derived GSDMB, promoting pyroptosis of cancer cells, bactericidal processes, and epithelial restitution and wound repai
- Several opportunities for controlling GSDMB function exists, and at different levels (e.g., as a consequence of GSDMB polymorphisms, by alternative splicing, and through regulation of its cleavage, among others). We are at the advent of discovery regarding GSDMB’s biology, with recent studies providing important insights into the mechanism(s) of such regulation and its specific roles during health and disease states.
3:00 pm IMM-004 small molecule series that inhibits NLRP3, NLPR1, NLRC4 & AIM2
Synopsis
- Multiple inflammasomes (NLRP3, NLRP1, NLRC4, AIM2) drive many rare and prevalent diseases such as neuroinflammatory, cardiometabolic and rheumatic disease. While drugging only one inflammasome (NLRP3) has been the key focus in the inflammasome space, NLPR3 inhibition alone may not be sufficient to control many diseases where other inflammasomes are activated or cross-activated. Thus, multi-inflammasome inhibition strategy could be essential for achieving more effective disease control
- Discovering IMM-004 series of molecules that control IL-1b and IL-18 formation from NLRP3, NLRP1, NLRC4, and AIM2
- IMM-004 series are novel small molecules, orally bioavailable and brain penetrating. IMM-004 series molecules are being explored for neuro-inflammatory, cardiometabolic and rheumatic diseases
3:30 pm Understanding the Inner Workings of the Inflammasome Engine
Synopsis
- Presenting how NLRP3 becomes activated by
conformational change and trafficking - Elucidating how ligand sensing induces NLRP6 phase
separation, which in turn promotes inflammasome
formation and signaling in vitro and in vivo
Advances in Proof-of-Concept Trials in Various Diseases
2:00 pm From Inflammasome to Mitochondria, Novel Therapies for Neurodegenerative Diseases
Synopsis
- Inflammasome activation is a key drive of pathology in multiple neurodegenerative diseases
- Targeting both inflammasomes and mitochondria prove efficacious in reducing pathology in multiple murine disease models.
- We have developed a novel, brain-penetrant inhibitor of mitochondrial fragmentation that limits inflammation and reduces Parkinson’s Disease pathology
2:30 pm Identification of a Novel Class of Highly Potent, CNS-Penetrant NLRP3 Specific Inhibitors with Excellent Druglike Physical Features
Synopsis
- Learn how bioAge’s AI-driven discovery platform, based on analysis of proprietary human aging cohort data, revealed that NLRP3 levels rise with age and are positively correlated with all-cause mortality and cognitive decline
- Discover how to identify novel NLRP3 inhibitors, BioAge screened billions of molecules in a DNA-encoded library (DEL) for compounds that bind purified NLRP3 protein. Further chemical modifications show how is possible to functionally inhibit the NLRP3 inflammasome in vivo and in vitro with comparable or superior potency relative to publicly known inhibitors
- Review how the newly identified molecules have novel structures and chemical properties, distinct from those of publicly known NLRP3 inhibitors, with features allowing favorable oral bioavailability and BBB penetration
3:00 pm Regulation of the NLRP3 Inflammasome by Anakinra Treatment in Human Disease
Synopsis
- Exploring ex vivo tracking of inflammasome activation in human samples
- Assessing anakinra treatment in humans on inflammasome activation
- Discussing multi-inflammasome inhibitor development
3:30 pm Inflammasomes and the Control of Anti-Tumor Immunity
Synopsis
- Explore how Inflammasomes can drive interleukin-1
release from living dendritic cells - Learn how Inflammasomes in dendritic cells promote
memory T cell activation - Discuss how Inflammasomes in dendritic cells are critical
for anti-tumor immunity