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.
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[1][2].
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:
FAAH knockout mice and FAAH inhibitors have demonstrated:
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:
Phase 1 trial (NCT07142044):
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:
In neurodegenerative diseases, sEH expression is elevated, leading to reduced EET levels and increased neuroinflammation. sEH inhibition has demonstrated:
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:
| 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 | — |
EicOsis is pursuing a multi-pronged clinical strategy for EC5026 in PD:
The company plans to initiate a Phase 2 trial following successful Phase 1 completion, with adaptive design to enable dose optimization and patient stratification.
FAAH inhibition is well-suited for combination with standard-of-care PD therapies:
| 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:
EicOsis believes its compound and trial design address these limitations:
EicOsis has built a strong IP portfolio:
EicOsis is pursuing a traditional biotech development path:
The company has raised over $40M in venture funding to advance its pipeline.
Ferrara L, Tomaselli V, Al Husseini D, Kuo YM, Palomo V, St. Laurent R, O’Leary C, Wargovich M, Dawson G. FAAH inhibition as a therapeutic approach for Parkinson's disease. J Parkinsons Dis. 2021. ↩︎
Basavarajappa BS, Shivakumar B, Joshi V, Subbanna S. Endocannabinoid system in Parkinson's disease: The role of FAAH. Neurobiol Dis. 2017. ↩︎