NLRP3

CNS-penetrant NLRP3 inhibitor

Targeting metabolic diseases and neuroinflammation

A key mediator of chronic inflammation that develops with age

NLRP3 is a critical component of the inflammasome, a protein complex that assembles in response to infection and tissue damage and results in inflammation needed to promote healing. However, chronic inflammasome activation leads to pathologic inflammation that drives a vast number of immunologic and fibrotic disorders.

Analysis of BioAge’s proprietary longitudinal human aging cohorts revealed that NLRP3 levels rise with age and are associated with all-cause mortality.

BioAge has discovered a family of chemically novel NLRP3 inhibitors. We have advanced compounds that are both potent and highly brain penetrant, with potential to address a range of metabolic and neuroinflammatory conditions.

Program
Mechanism of Action
Route of administration
Indication
Status
NLRP3
NLRP3 inhibitor
Oral
Metabolic disease & neuroinflammation
IND-enabling pointer
Discoverу Lead Op IND-enabling Ph 1 Ph 2 Ph 3
Program

NLRP3

Mechanism of Action NLRP3 inhibitor
Route of administration Oral
Indication Metabolic disease & neuroinflammation
Status
IND-enabling pointer
Discoverу Lead Op IND-enabling Ph 1 Ph 2 Ph 3
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Our NLRP3 inhibitors have the potential to corrects

chronic inflammasome activation that is associated

with aging and drives a broad range of diseases

Our NLRP3 inhibitors have the potential

to corrects chronic inflammasome

activation that is associated with aging and drives a broad range of diseases

Our NLRP3 inhibitors have

the potential to corrects chronic

inflammasome activation that is

associated with aging and drives a broad range of diseases

Young
Absence of immune stimuli
Inactive NLRP3
Immune stimuli
NLRP3 inflammasome assembly and activation
Acute cytokine release: (IL-1β, IL-18)

Acute inflammation to enable immune response to pathogen

Old
Immune system priming: ↑ NLRP3, ASC, pro-caspase
  • NLRP3
  • ASC
  • Pro-caspase-1
Overactive NLRP3 inflammasome
Exaggerated proinflammatory signals: Cytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3

Prolonged inflammation, even in the absence of pathogen

Acute cytokine release: (IL-1β, IL-18)

Acute inflammation to enable immune response to pathogen

Exaggerated proinflammatory signals: Cytokine release (IL-1β, IL-18) and pyroptosis (DAMPs)
NLRP3

Prolonged inflammation, even in the absence of pathogen

BioAge collaborator spotlight

Chronic activation of the NLRP3 inflammasome is associated with aging and is a major contributor to the pathologic inflammation that drives or exacerbates multiple metabolic, immunologic, and fibrotic disorders, as well as neurodegenerative conditions such as Parkinson’s and Alzheimer’s. Inhibition of NLRP3 using small-molecules thus has the potential to treat a broad spectrum
of age-related diseases.

Rebecca Coll, PhD

Wellcome Wolfson Institute for Experimental Medicine Queen's University Belfast
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