EC5026 / EicOsis - LARVOL DELTA

Inhibition of soluble epoxide hydrolase enhances the cerebral vascular function and attenuates cognitive impairment in diabetes-associated ADRD (Neuroscience 2025) - "These findings suggest that EC5026, like TPPU, restores cognitive function and cerebrovascular integrity in diabetes-related ADRD. Supporting its therapeutic potential as a human sEH inhibitor for treating vascular contributions to cognitive impairments."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • NOTCH1

Safety, Tolerability and Exploratory Efficacy of EC5026 in Parkinson's Disease (STEP Study) (clinicaltrials.gov) - P1/2 | N=18 | Recruiting | Sponsor: EicOsis Human Health Inc.

New P1/2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Inhibition of Soluble Epoxide Hydrolase Prevents Docetaxel-Induced Painful Peripheral Neuropathy. (PubMed, Int J Mol Sci) - "There were no motor effects of the compound, and the formulated drinking water provided favorable exposure. These results demonstrated that EC5026 administered prophylactically was both analgesic and able to limit the severity of mechanical and cold sensitivities in the docetaxel CIPN rat model."

Journal • Genito-urinary Cancer • Oncology • Pain • Peripheral Neuropathic Pain • Prostate Cancer • Solid Tumor

Novel Soluble Epoxide Hydrolase Inhibitor for Neuropathic Pain in Patients With Spinal Cord Injury (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: EicOsis Human Health Inc. | Trial primary completion date: Jun 2026 ➔ Dec 2026

Trial primary completion date • CNS Disorders • Musculoskeletal Diseases • Neuralgia • Orthopedics • Pain

Discovery of Phenylacylpiperidine as Novel sEH Inhibitors through Scaffold Hopping of Natural Stilbene. (PubMed, J Med Chem) - "Notably, 77 demonstrated additional interactions with sEH compared to TPPU, and uniquely enhanced anti-inflammatory factors, including EET levels and IL-10, a capability not observed with EC5026. Moreover, 77 showed excellent pharmacokinetics and safety, positioning it as a promising candidate for treating both acute and chronic inflammatory diseases, including rheumatoid arthritis, leveraging phenylacylpiperidine scaffolds in sEH-targeted therapies."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • IL10

Novel Soluble Epoxide Hydrolase Inhibitor for Neuropathic Pain in Patients with Spinal Cord Injury (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: EicOsis Human Health Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2025 ➔ Dec 2026 | Initiation date: Dec 2024 ➔ Apr 2025 | Trial primary completion date: Nov 2025 ➔ Jun 2026

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Musculoskeletal Diseases • Neuralgia • Orthopedics • Pain

Inhibitors of soluble epoxide hydrolase and cGAS/STING repair defects in amyloid-β clearance underlying vascular complications of Alzheimer's disease. (PubMed, J Alzheimers Dis) - "The sEHI inhibitor EC5026 and the STING inhibitor H-151 increased macrophage uptake and degradation of Aβ. EC5026 administration was safe in normal volunteers. EC5026 together with ω-3 PUFA supplementation are indicated for in a clinical trial in patients with mild cognitive impairment."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Vasculitis • STING

Drug Development. (PubMed, Alzheimers Dement) - "In summary, we demonstrate that EPHX2 (sEH) is a promising novel anti-inflammatory target for AD and the EC5026 (a first-in-class, picomolar sEH inhibitor) significantly improves cognition in the 5xFAD mouse model. Future functional observations and clinical trials are warranted to validate the causal relationship of EC5026 in potential treatment of AD."

Journal • Alzheimer's Disease • CNS Disorders

Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Oral EC5026 in Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: EicOsis Human Health Inc. | Recruiting ➔ Completed | Trial completion date: Jun 2024 ➔ Mar 2024

Trial completion • Trial completion date

Novel Soluble Epoxide Hydrolase Inhibitor for Neuropathic Pain in Patients With Spinal Cord Injury (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: EicOsis Human Health Inc. | Trial completion date: Jul 2025 ➔ Dec 2025 | Initiation date: Jul 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2025 ➔ Nov 2025

Trial completion date • Trial initiation date • Trial primary completion date • CNS Disorders • Musculoskeletal Diseases • Neuralgia • Orthopedics • Pain • CRP • IL6 • TNFA

Randomized, double-blind, phase 1a single-ascending dose and food effect studies assessing safety and pharmacokinetics of EC5026 in healthy volunteers. (PubMed, Clin Transl Sci) - "in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity."

Clinical • Journal • P1 data • PK/PD data • Pain

Soluble epoxide hydrolase (sEH) is a novel anti-inflammatory target and a first-in-class, picomolar sEH inhibitor (EC5026) improves cognition in a mouse model of Alzheimer’s disease (AAIC 2024) - "In summary, we demonstrate that EPHX2 (sEH) is a promising novel anti-inflammatory target for AD and the EC5026 (a first-in-class, picomolar sEH inhibitor) significantly improves cognition in the 5xFAD mouse model. Future functional observations and clinical trials are warranted to validate the causal relationship of EC5026 in potential treatment of AD."

Preclinical • Alzheimer's Disease • CNS Disorders

Autologous macrophages stimulated by epoxides of polyunsaturated fatty acids and protected by inhibitors of soluble epoxide hydrolase or cGAS/STING pathway repair amyloid-β pathology in the Alzheimer's disease (AD) brain. (AAIC 2024) - "Inhibiting macrophage inflammation by the sEH receptor inhibitors TPPU and EC5026 or the STING inhibitor H-151 in AD macrophages could restore cognition in AD patients."

Alzheimer's Disease • CNS Disorders • Inflammation • Vasculitis • PTGER4

Alzheimer’s disease genetics and real-world patient data fuel target and drug discovery in European and African American Ancestries using AI/ML approaches (AAIC 2024) - "We demonstrated that TPPU (a nanomolar-EPHX2 inhibitor) blocked deterioration in hippocampal-dependent cognitive ability in a TgF344-AD rat model and EC5026 (a first-in-class, picomolar EPHX2 inhibitor) improves cognition in a 5xFAD mouse model...We found that usage of either apixaban (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.69–0.80) and amlodipine (HR = 0.91, 95%CI 0.88–0.94) were significantly associated with reduced progression to AD. Combining genetics and real-world patient data identifies ancestry-specific therapeutic targets and medicines for AD. Further functional and clinical validation of candidate targets and drugs in ethnically diverse population are warranted."

Clinical • Real-world • Real-world evidence • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Novel Soluble Epoxide Hydrolase Inhibitor for Neuropathic Pain in Patients With Spinal Cord Injury (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: EicOsis Human Health Inc.

New P1 trial • CNS Disorders • Musculoskeletal Diseases • Neuralgia • Orthopedics • Pain • CRP • IL6 • TNFA

Identification and characterization of the in-vivo metabolites of the novel soluble epoxide hydrolase inhibitor EC5026 using liquid chromatography quadrupole time of flight mass spectrometry. (PubMed, J Pharm Biomed Anal) - "Further, the docking study revealed that the mono-hydroxylated and terminally desaturated metabolites possess better binding affinity than the parent drug. Therefore, these metabolites may hold sEH inhibition potential and can be followed through future research."

Journal • Preclinical • Inflammation • Neuralgia • Pain

Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Oral EC5026 in Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Recruiting | Sponsor: EicOsis Human Health Inc. | Not yet recruiting ➔ Recruiting | Phase classification: P1b ➔ P1

Enrollment open • Phase classification

Safety, Tolerability, Pharmacokinetics and Food Effects of Oral EC5026 in Healthy Subjects (clinicaltrials.gov) - P1 | N=18 | Completed | Sponsor: EicOsis Human Health Inc. | Recruiting ➔ Completed | Phase classification: P1a ➔ P1

Phase classification • Trial completion

EicOsis Initiates Phase 1b Clinical Trial of EC5026 (PRNewswire) - "EicOsis Human Health...announced the next step in its ongoing human clinical trials: the initiation of Phase 1b multiple-ascending dose clinical trial to test the safety of its drug candidate, EC5026...The double-blind, placebo-controlled Phase 1b study is designed to investigate the safety and pharmacokinetics of daily doses of EC5026 or placebo over seven days. Initial results show no apparent changes in vital signs, behavior effects, or clinically significant adverse effects in any subjects."

Trial status • Pain

Discovery of a novel lead characterized by a stilbene-extended scaffold against sepsis as soluble epoxide hydrolase inhibitors. (PubMed, Eur J Med Chem) - "In addition, 70P exhibits equal IC50 value (1.5 nM) on inhibiting human sEH as EC5026 (1.7 nM). In conclusion, the natural scaffold-extended sEH inhibitor 70P has the potential to become a new promising lead for addressing the unmet medical need in sepsis treatment, which highlighted the importance of natural skeleton in developing sEH inhibitors."

Journal • Infectious Disease • Septic Shock • IL6 • TNFA

Development and validation of LC-MS/MS method for estimating the pharmacokinetics, protein binding, and metabolic stability of soluble epoxide hydrolase inhibitor EC5026. (PubMed, J Pharm Biomed Anal) - "The rat plasma protein binding was estimated to be 96.24% ± 0.97% and 96.38% ± 0.56% at 1 µM and 10 µM concentrations, respectively. The developed analytical method is expected to facilitate future pre-clinical, clinical investigations of EC5026."

Journal • PK/PD data • Pain

Safety, Tolerability, and Pharmacokinetics of Multiple Doses of Oral EC5026 in Healthy Subjects (clinicaltrials.gov) - P1b | N=16 | Not yet recruiting | Sponsor: EicOsis Human Health Inc.

New P1 trial

Quantification of soluble epoxide hydrolase inhibitors in experimental and clinical samples using the nanobody-based ELISA. (PubMed, J Pharm Anal) - "Using soluble epoxide hydrolase (sEH) inhibitors (EC5026 and TPPU) as examples, we report development of a nanobody-based enzyme-linked immunosorbent assay (ELISA) for such small molecules and its use to accurately quantify the drug chemicals in human samples...This work illustrates that nanobody based assays offer alternative and supplementary analytical tools to mass spectrometry for monitoring small molecule medicines during clinical development and therapy. Attributes of nanobody based pharmaceutical assays are discussed."

Journal

Soluble epoxide hydrolase inhibition alleviates chemotherapy induced neuropathic pain. (PubMed, Front Pain Res (Lausanne)) - "Doses of EC5026, an IND candidate intended to treat neuropathic pain, elicited dose dependent analgesic responses in multiple models including platinum-based, taxane, and vinca alkaloid-based CIPN pain in Sprague Dawley rats. At the same time as a class, the sEHI are known to result in fewer debilitating side effects of other analgesics, likely due to their novel mechanism of action. Overall, the observed dose-dependent analgesia in both male and female rats across multiple models of chemotherapy induced neuropathic pain holds promise as a useful tool when translated to the clinic."

Journal • Addiction (Opioid and Alcohol) • Infectious Disease • Neuralgia • Novel Coronavirus Disease • Oncology • Pain • Peripheral Neuropathic Pain

A New Family of Subnanomolar inhibitors of Soluble Epoxide Hydrolase. (PubMed, FASEB J) - "Although several potent sEH inhibitors (sEHI) have been developed, including clinical candidates AR9281, GSK2256294, and EC5026, so far no sEHI has reached the market. Biol. 2020, 1274, 71-99."

Journal • Inflammation • Pain