SBIR-STTR Award

Pain is a serious health problem affecting a large proportion of the general population. The burden of painful conditions on the individuals and the society follow a rising trajectory because of the paucity of effective and reasonably safe pharmaceuticals that are needed globally. Aging population and diabetes epidemic are two key factors that drive the number of people that will need efficacious analgesics. More than 75% of the analgesic market in volume is dominated by cyclooxygenase inhibitors. However lack of efficacy in neuropathic pain and side effects limit their use. Other approved therapeutics also suffers from lack of efficacy and diverse and serious side effects. This underlines the need to discover novel therapeutic agents to alleviate pain. In order to meet this need, Eicosis' overall objective is the development of a novel promising class of orally active analgesic drug that targets the soluble epoxide hydrolase (sEH), a new therapeutic target for pain. The inhibitors of sEH are not only more efficacious than COX inhibitors on inflammatory pain, but also they block intractable neuropathic pain more efficaciously than commercial standards gabapentin and pregabalin without the motor side effects. In this proposal, Eicosis will identify and select an IN candidate and a back-up compound for the treatment of painful conditions.

Public Health Relevance Statement:


Public Health Relevance:
Pain is a major health problem. Although a number of treatment options exist, most patients suffer from unfavorable side effects and limited efficacy. The lead compounds developed in this proposal have the potential to overcome these problems and deliver a novel solution to effectively treat chronic and neuropathic pain.

Project Terms:
Adverse effects; Affect; aging population; Analgesics; Anti Inflammatory Analgesics; Anti-inflammatory; Anti-Inflammatory Agents; Arachidonic Acids; Back; Biological Assay; Blood; California; Canis familiaris; Characteristics; chronic neuropathic pain; Clinical; Clinical Trials; Collaborations; Coxibs; Cross-Over Studies; Cyclooxygenase Inhibitors; Cytochromes; Data; Development; Diabetes Mellitus; diabetic patient; Diagnosis; Dinoprostone; Dose; Double-Blind Method; drug candidate; drug development; Drug Kinetics; drug standard; Drug Targeting; Enzymes; Epidemic; Epoxide hydrolase; Equus caballus; Fatty Acids; Felis catus; Freedom; Funding; gabapentin; General Population; Half-Life; Health; Homeostasis; Housing; In Vitro; in vitro Assay; in vivo; Individual; Industry; Inflammation; Inflammatory; inflammatory neuropathic pain; inflammatory pain; inhibitor/antagonist; International; Lead; Legal patent; Libraries; Licensing; Lipoxygenase; Marketing; Mediation; meetings; Modeling; Monitor; Motor; new therapeutic target; Nociception; Non-Rodent Model; Non-Steroidal Anti-Inflammatory Agents; novel; novel therapeutics; Oral; Oral Administration; Pain; painful neuropathy; Pathway interactions; Patient Self-Report; Patients; Peripheral Nervous System Diseases; Pharmacologic Substance; Phase; Placebos; Plasma; pre-clinical; pregabalin; Process; programs; Prostaglandin-Endoperoxide Synthase; Public Domains; public health relevance; Randomized; Rights; Rodent Model; screening; Seeds; selective expression; Societies; Solutions; Streptozocin; Structure; System; Technology; Testing; Therapeutic; Therapeutic Agents; Tissues; Toxic effect; Universities; Work

With this proposal we aim to further the development of novel and safe oral inhibitors of sEH for the treatment of peripheral neuropathy in diabetic patients. Preclinical studies with our candidate EC5026 demonstrated efficacy for diabetic neuropathy. EicOsis has selected EC5026 for its efficacy with good PK/ADME properties and stability to enter further development stages for this indication. EicOsis also tested the compound and a backup in vitro for off target effects against an array of enzymes, determined the potential inhibition of major cytochrome P450 enzymes, and tested for de-risking with a contract research laboratory. EicOsis has used these data as a basis for an application to work with Blueprint Development Teams to create a development plan and initiate studies to test the safety of EC5026 in Phase 1 clinical trials. To further develop the compounds selected from the completed Phase I application we propose here to radiolabel the candidate and backup to carry out detailed metabolism studies and develop the label as a tracer for human Phase I clinical trial. Additionally we propose to use conventional material to test for off-target toxicity in vivo and to explore the breadth of activity of the inhibitors in alternate pain models. The studies are designed to address understanding metabolism and the spectrum of activity which if lacking often prevent drugs from being developed. The results will empower scientists in the pharmaceutical industry with critical data that speaks to the wider spectrum of activity of sEH inhibitors as analgesics of the future.

Public Health Relevance Statement:


Public Health Relevance:
Data collected over the past decade indicate the unique characteristics of inhibitors of sEH as analgesics. The overarching goal of EicOsis is to develop a drug candidate for IND enabling studies for the treatment of neuropathic pain. Here we outline studies to further explore the in vivo metabolism and potential off target toxicity of the sEH inhibitors as well as their broader efficacy in alternate pain models.

Project Terms:
accelerator mass spectrometry; Addictive Behavior; Address; Adverse effects; Analgesics; Aromatic Amines; Back; base; Benchmarking; Biological Assay; Biology; Blood - brain barrier anatomy; Brain; cancer pain; Carbon; Carbon Dioxide; Cardiotoxicity; Characteristics; Chemicals; Chemistry; Clinic; Clinical; Cytochrome P450; Data; Development; Development Plans; Diabetic Neuropathies; diabetic patient; Dose; drug candidate; Drug Industry; empowered; Enzyme Tests; Enzymes; Epoxide hydrolase; Equilibrium; Fibromyalgia; Future; gastrointestinal; Goals; Grant; Hemostatic function; Human; Hyperalgesia; In Vitro; in vivo; Inflammation; inhibitor/antagonist; Label; Laboratories; Laboratory Research; Lesion; Locomotion; metabolic abnormality assessment; Metabolism; Methods; Modeling; Monitor; Movement; Neuraxis; Neuropathy; Non-Steroidal Anti-Inflammatory Agents; novel; Opioid; Oral; Organ; orofacial; Pain; Pain management; painful neuropathy; Penetration; Peripheral; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Pharmacotherapy; Phase; phase 1 study; Phase I Clinical Trials; physical property; Postoperative Pain; preclinical study; prevent; Program Development; programs; Property; public health relevance; Radiolabeled; radiotracer; Refractory; Research Contracts; Research Design; Reserpine; Risk; Rodent; Route; Safety; safety testing; scale up; Scientist; Small Business Innovation Research Grant; Speed (motion); Staging; Testing; Therapeutic; Toxic effect; Toxicology; Tracer; United States National Institutes of Health; Urea; Work