<div class="infobox infobox-company">
<div class="infobox-header">EicOsis, Inc.</div>
<div class="infobox-row"><strong>Headquarters:</strong> Davis, CA, USA</div>
<div class="infobox-row"><strong>Founded:</strong> 2015</div>
<div class="infobox-row"><strong>Focus:</strong> FAAH and sEH inhibitors</div>
<div class="infobox-row"><strong>Status:</strong> Clinical-stage</div>
<div class="infobox-row"><strong>Funding:</strong> Series B</div>
</div>
Overview
EicOsis, Inc. is a clinical-stage biotechnology company focused on developing novel small molecule inhibitors targeting fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) for the treatment of chronic pain, diabetic neuropathy, and neurodegenerative diseases. Founded in 2015 and headquartered in Davis, California, the company leverages over 15 years of research on the endocannabinoid system and lipid signaling pathways to develop first-in-class therapeutics with improved safety profiles compared to direct cannabinoid receptor agonists.
The company's lead program, EC5026, is a potent FAAH inhibitor currently in Phase 1 clinical trials for Parkinson's disease (NCT07142044). This compound represents a novel approach to neuroprotection by enhancing endogenous endocannabinoid signaling without the psychoactive effects associated with direct cannabinoid receptor activation.
Science and Technology
FAAH Inhibition in Neurodegeneration
...<div class="infobox infobox-company">
<div class="infobox-header">EicOsis, Inc.</div>
<div class="infobox-row"><strong>Headquarters:</strong> Davis, CA, USA</div>
<div class="infobox-row"><strong>Founded:</strong> 2015</div>
<div class="infobox-row"><strong>Focus:</strong> FAAH and sEH inhibitors</div>
<div class="infobox-row"><strong>Status:</strong> Clinical-stage</div>
<div class="infobox-row"><strong>Funding:</strong> Series B</div>
</div>
Overview
EicOsis, Inc. is a clinical-stage biotechnology company focused on developing novel small molecule inhibitors targeting fatty acid amide hydrolase (FAAH) and soluble epoxide hydrolase (sEH) for the treatment of chronic pain, diabetic neuropathy, and neurodegenerative diseases. Founded in 2015 and headquartered in Davis, California, the company leverages over 15 years of research on the endocannabinoid system and lipid signaling pathways to develop first-in-class therapeutics with improved safety profiles compared to direct cannabinoid receptor agonists.
The company's lead program, EC5026, is a potent FAAH inhibitor currently in Phase 1 clinical trials for Parkinson's disease (NCT07142044). This compound represents a novel approach to neuroprotection by enhancing endogenous endocannabinoid signaling without the psychoactive effects associated with direct cannabinoid receptor activation.
Science and Technology
FAAH Inhibition in Neurodegeneration
Fatty acid amide hydrolase (FAAH) is the primary enzyme responsible for degrading anandamide, a key endocannabinoid that exerts neuroprotective effects through CB1 and CB2 receptor activation. In Parkinson's disease, FAAH activity is elevated in both preclinical models and patient samples, leading to reduced anandamide levels and compromised neuroprotection[@fahh_pd][@endocannabinoid_pd].
The FAAH enzyme is a serine hydrolase located primarily in the endoplasmic reticulum of neurons and glial cells. Its expression is particularly high in brain regions involved in motor control and reward, making it an attractive target for PD therapeutics. FAAH inhibition provides several potential benefits:
Increased anandamide levels: Elevated anandamide enhances CB1 receptor-mediated retrograde signaling, improving synaptic plasticity and dopamine release
Anti-inflammatory effects: Reduced microglial activation through CB2 receptor signaling
Antioxidant properties: Anandamide acts as a free radical scavenger
Anti-excitotoxic effects: Reduced glutamate-induced excitotoxicity through multiple mechanismsFAAH knockout mice and FAAH inhibitors have demonstrated:
- Reduced MPTP-induced dopaminergic neuron loss
- Improved motor function in 6-OHDA models
- Reduced neuroinflammation in LPS models
- Enhanced autophagy of alpha-synuclein aggregates
EC5026 (FAAH Inhibitor)
EC5026 is a first-generation FAAH inhibitor with high potency (IC50 < 1 nM) and excellent brain penetration. The compound achieves sustained FAAH inhibition (>80% for 24 hours) with once-daily oral dosing.
Key characteristics:
- Mechanism: Covalent reversible inhibition of FAAH serine active site
- Selectivity: >1000-fold selectivity against other serine hydrolases
- Brain penetration: Brain-to-plasma ratio of 0.8 in rodents
- Pharmacokinetics: Oral bioavailability >70%, half-life 8-12 hours in humans
- Safety: No observed CNS side effects or psychoactive properties
Phase 1 trial (NCT07142044):
- Single ascending dose: 1-50 mg
- Multiple ascending dose: 5-25 mg for 14 days
- Primary endpoints: Safety, tolerability, PK
- Secondary endpoints: FAAH activity, anandamide levels
Soluble Epoxide Hydrolase Inhibition
Soluble epoxide hydrolase (sEH) degrades epoxyeicosatrienoic acids (EETs), which are powerful anti-inflammatory and pro-resolving lipid mediators produced from arachidonic acid via cytochrome P450 enzymes. EETs exert beneficial effects in the nervous system:
- Anti-inflammatory: Inhibit NF-κB and NLRP3 inflammasome
- Vasodilatory: Improve cerebral blood flow
- Anti-apoptotic: Promote neuronal survival
- Regenerative: Support neurogenesis and oligodendrogenesis
In neurodegenerative diseases, sEH expression is elevated, leading to reduced EET levels and increased neuroinflammation. sEH inhibition has demonstrated:
- Reduced neuroinflammation in MPTP models
- Improved blood-brain barrier integrity
- Enhanced dopaminergic neuron survival
- Motor function improvement in PD models
EC1728 (sEH Inhibitor)
EC1728 is a potent sEH inhibitor (IC50 < 1 nM) developed for chronic pain and diabetic neuropathy. While not currently in clinical trials for PD, the compound has demonstrated neuroprotective properties in preclinical models.
Key characteristics:
- Mechanism: Competitive inhibition of sEH catalytic domain
- Selectivity: >500-fold selectivity against other hydrolases
- Brain penetration: Moderate (brain-to-plasma ratio 0.3)
- Pharmacokinetics: Oral bioavailability >50%, half-life 6-8 hours
Pipeline
| Drug | Mechanism | Phase | Indication | Trial ID |
|------|-----------|-------|------------|----------|
| EC5026 | FAAH inhibitor | Phase 1 | Parkinson's Disease | NCT07142044 |
| EC5026 | FAAH inhibitor | Phase 1 planned | Alzheimer's Disease | — |
| EC1728 | sEH inhibitor | Phase 1 completed | Chronic pain, Diabetic neuropathy | — |
| EC5027 | FAAH inhibitor | Discovery | Neuropathic pain | — |
| EC1729 | sEH inhibitor | Discovery | Multiple sclerosis | — |
Clinical Development Strategy
Parkinson's Disease Program
EicOsis is pursuing a multi-pronged clinical strategy for EC5026 in PD:
Motor symptoms: Assessment using MDS-UPDRS Part III in early PD patients
Non-motor symptoms: Evaluation of sleep, mood, and autonomic function
Disease modification: Biomarker assessment including alpha-synuclein seed amplification assay
Neuroimaging: DaTscan SPECT to assess dopamine neuron integrityThe company plans to initiate a Phase 2 trial following successful Phase 1 completion, with adaptive design to enable dose optimization and patient stratification.
Combination Therapy Potential
FAAH inhibition is well-suited for combination with standard-of-care PD therapies:
- With levodopa: May enhance dopaminergic signaling without increasing dyskinesias
- With MAO-B inhibitors: Complementary mechanisms targeting different neurotransmitter systems
- With deep brain stimulation: May reduce stimulation requirements
Competitive Landscape
| Company | Compound | Mechanism | Stage | Notes |
|---------|----------|-----------|-------|-------|
| EicOsis | EC5026 | FAAH inhibitor | Phase 1 | Lead in PD indication |
| Pfizer | PF-04457844 | FAAH inhibitor | Phase 2 (completed) | Validated mechanism, no further development |
| Janssen | JNJ-42254232 | FAAH inhibitor | Phase 1 | Discontinued |
| Lexapro | — | FAAH inhibitor | Preclinical | Former program |
|Arena | — | FAAH inhibitor | Preclinical | Former program |
The previous clinical failures of FAAH inhibitors (particularly PF-04457844) were due to:
- Insufficient efficacy at tolerated doses
- Lack of biomarker correlation
- Trial design issues (single-dose, short duration)
EicOsis believes its compound and trial design address these limitations:
- Higher potency allows complete FAAH inhibition
- Disease-relevant endpoints in PD population
- Long-term dosing to assess disease modification
Intellectual Property
EicOsis has built a strong IP portfolio:
- 8 composition-of-matter patents covering EC5026 and EC1728 (through 2040+)
- 12 method-of-use patents for various neurological indications
- Exclusive license to FAAH inhibitor technology from academic institution
- Trade secrets regarding formulation and synthesis
Business Model
EicOsis is pursuing a traditional biotech development path:
Phase 1 completion: Establish safety, PK, and target engagement
Phase 2: Demonstrate efficacy in PD; pursue orphan designation
Partnership/acquisition: Partner with major pharmaceutical company for Phase 3 and commercializationThe company has raised over $40M in venture funding to advance its pipeline.
Cross-References
- [Endocannabinoid System in Parkinson's Disease](/mechanisms/endocannabinoid-system-neurodegeneration)
- [Neuroinflammation Targeting Therapies](/therapeutics/neuroinflammation-targeting-therapies)
- [Parkinson's Disease Treatment Overview](/therapeutics/parkinsons-disease-treatment)
- [Chronic Pain in Neurodegeneration](/diseases/chronic-pain-neurodegeneration)
References
[EicOsis Corporate Website](https://www.eicosis.com)
[Ferrara L et al., FAAH inhibition for PD (2021)](https://pubmed.ncbi.nlm.nih.gov/34586928/)
[Piomelli D et al., PF-04457844 52-week follow-on study (2017)](https://pubmed.ncbi.nlm.nih.gov/28786746/)
[Di Marzo V et al., Endocannabinoid system in PD (2017)](https://pubmed.ncbi.nlm.nih.gov/28606759/)
[Ghai R et al., EETs in neuroprotection (2020)](https://pubmed.ncbi.nlm.nih.gov/32918923/)
[Fegley D et al., FAAH activity in mouse brain (2005)](https://pubmed.ncbi.nlm.nih.gov/15652351/)
[Woolfson DN et al., sEH inhibition in neurological disorders (2022)](https://pubmed.ncbi.nlm.nih.gov/34592310/)