Nitroalkene Signaling Therapeutics

Creegh
Pharma

Clinical-stage therapeutics derived from endogenous nitroalkene signaling biology.

Clinical-stage platform
Two Phase 2 Programs
Dopaminergic neuron preservation in SNpc

Creegh assets demonstrate preservation of dopaminergic neurons in the substantia nigra pars compacta (SNpc), a primary site of neuronal loss in Parkinson's disease, through regulation of inflammatory and oxidative stress signaling.

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Platform

Endogenous signals.
Engineered medicines.

Nitroalkenes are endogenous signaling mediators regulating pathways that govern inflammation, metabolism, and cellular stress.

Creegh Pharma is advancing a portfolio of nitroalkene therapeutics targeting inflammatory and degenerative disease pathways.

The nitroalkene therapeutic class was first discovered and characterized by Bruce A. Freeman and Francisco J. Schopfer, co-founders of Creegh Pharma, whose research over four decades — 500+ publications and 75,000+ citations — established the scientific foundation of electrophilic lipid signaling.
Nitroalkene Signaling Cascade
Nitroalkene Signaling
Mediator
→
Electrophilic
Signaling
Nrf2
Activation
→
NF-κB
Inhibition
PPARγ
Modulation
→
HSP
Induction
Inflammation · Metabolism · Cellular Stress
Endogenous signaling mediators — electrophilic fatty acid derivatives produced during inflammation & metabolism.
↑ Select any node to explore its mechanism.
Clinical Programs

One drug family.
Multiple disease targets.
Two active Phase 2 trials.

Phase 2

Steroid and Bronchodilator-Resistant
Obesity-Associated Asthma

Randomized, blinded, placebo-controlled study evaluating airway physiology, inflammatory signaling biomarkers, and pulmonary epithelial gene expression.

Airway Physiology Inflammatory Biomarkers Gene Expression Placebo-Controlled
Phase 2a

Parkinson's
Disease

Randomized study evaluating CNS penetration, target engagement, and mechanistic biomarker responses using advanced neuroimaging and biofluid endpoints.

CNS Penetration Target Engagement Neuroimaging Biofluid Endpoints
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Phase 2 · Active Enrollment

Steroid & Bronchodilator-Resistant
Obesity-Associated Asthma

A randomized, double-blinded, placebo-controlled study evaluating a Creegh nitroalkene therapeutic in patients with severe obesity-associated asthma who have failed standard-of-care corticosteroid and bronchodilator therapy.

Phase 2
Clinical Stage
DB-PC
Double-Blind
Placebo-Controlled
3
Primary Endpoint
Domains
Disease Rationale

Unmet Medical Need

Obesity-associated asthma represents a distinct phenotype characterized by non-eosinophilic, neutrophilic-predominant airway inflammation. This population demonstrates markedly reduced responsiveness to inhaled corticosteroids and bronchodilators — leaving millions of patients without effective therapeutic options.

Nitroalkene Mechanism

Nitroalkene therapeutics address the underlying NF-κB–driven inflammatory cascade that characterizes this phenotype. By modulating innate immune activation and oxidative stress simultaneously through Nrf2 and PPARγ pathways, they target inflammation at its metabolic root rather than downstream symptoms.

Study Endpoints
Airway Physiology

Spirometry, bronchial hyperresponsiveness, and oscillometry assessments measuring functional respiratory improvement across treatment and placebo arms.

Inflammatory Biomarkers

Serum and induced sputum cytokine panels including IL-6, IL-8, TNF-α, and eicosanoid metabolite profiling to establish mechanistic target engagement.

Gene Expression

Pulmonary epithelial transcriptomic analysis via bronchoscopic sampling to characterize Nrf2-regulated antioxidant response element (ARE) gene induction.

Safety & Tolerability

Comprehensive safety monitoring including lipid and metabolic panels, hepatic function, and adverse event surveillance across all enrolled subjects.

Scientific Context

The nitroalkene class represents a novel approach to asthma therapeutics by targeting the metabolic-inflammatory interface. Unlike biologic therapies targeting single cytokine axes, nitroalkene signaling mediators engage a broad anti-inflammatory program through simultaneous activation of Nrf2, inhibition of NF-κB, and PPARγ modulation — addressing the multi-pathway dysregulation characteristic of obesity-driven airway disease.

This approach is grounded in over four decades of foundational research from Creegh founder Bruce A. Freeman and colleagues, who first characterized endogenous nitroalkene production and their roles as endogenous adaptive signaling mediators during inflammatory and metabolic stress.

Phase 2a · Active

Parkinson's
Disease

A randomized study evaluating CNS penetration, target engagement, and mechanistic biomarker responses of a Creegh nitroalkene therapeutic in Parkinson's disease, using advanced neuroimaging and biofluid endpoints to establish proof-of-mechanism in the CNS.

Phase 2a
Clinical Stage
CNS
Target Tissue
Penetration
4
Primary Endpoint
Domains
Disease Rationale

Neuroinflammation & Oxidative Stress

Parkinson's disease pathogenesis involves the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, driven by mitochondrial dysfunction, oxidative stress, and neuroinflammatory activation. Preclinical data demonstrate robust preservation of SNpc dopaminergic neurons by Creegh nitroalkene therapeutics.

Mechanistic Rationale

Nitroalkene therapeutics engage multiple neuroprotective pathways simultaneously: Nrf2-driven antioxidant gene induction, HSP70 upregulation for protein quality control, and NF-κB suppression to reduce microglial neuroinflammation — addressing convergent mechanisms of dopaminergic vulnerability.

Study Endpoints
CNS Penetration

CSF and plasma pharmacokinetic sampling to establish CNS drug exposure and blood-brain barrier penetration kinetics at therapeutic doses.

Target Engagement

Nrf2 pathway activation measured via ARE-gene expression in peripheral blood mononuclear cells as a surrogate, alongside CSF biomarker profiling.

Neuroimaging

Advanced MRI and DaTscan protocols to evaluate nigrostriatal integrity and dopaminergic terminal density, with longitudinal assessments across treatment arms.

Biofluid Endpoints

CSF and serum assays for α-synuclein, neurofilament light chain, inflammatory cytokines, and nitroalkene metabolite profiling to document mechanistic engagement.

Preclinical Foundation

Creegh nitroalkene assets have demonstrated preservation of dopaminergic neurons in the substantia nigra pars compacta in validated preclinical Parkinson's disease models. This neuroprotection was accompanied by suppression of neuroinflammatory markers and induction of Nrf2-regulated cytoprotective genes in CNS tissue.

The Phase 2a study translates these preclinical observations into a human proof-of-mechanism study, establishing whether CNS-relevant target engagement and mechanistic biomarker responses can be detected at therapeutic exposures — providing the evidentiary foundation for a subsequent efficacy-powered Phase 2b study.