Phase II Amount
$1,070,335
Project Summary / Abstract: Pain is currently the most prevalent, disabling, and costly health issue in our country, and this problem will continue to grow as our population ages. The societal impact of pain (e.g., treatment costs, work loss, decreased productivity, co-morbidities with addiction, depression and suicide) exceeds the annual combined costs of heart disease, diabetes, and cancer. Unfortunately, the drugs predominantly used to treat pain today, opioids, are addictive and require increasing dosages to obtain a given level of pain relief. The difficulties posed by opioid use are magnified tremendously by the strong potential for addiction and abuse. According to the Centers for Disease Control and Prevention, approximately 78 people die every day from overdoses related to prescription painkillers. These problems with opioids, and their limited efficacy over the longer term highlight the need for new pain medicines. The scientific purpose of this project is to conduct studies to advance a promising new pain therapeutic (CT-044), belonging to a novel chemotype / pharmacological class, into first-in-human studies. Our innovation is the discovery of the first non-metal based PN decomposition catalyst. The past decade has demonstrated that 1) free radicals contribute to pain and 2) their interactions with nociceptive sensory neurons in the peripheral nervous system perturb nociceptive signaling. Our goal is to move our lead molecule, CT-044 into the clinic through the investigational new drug enabling studies described in this proposal. As will be described in detail below, we have amassed an impressive preclinical data package on this lead asset showing that the compound is highly efficacious in incisional and inflammatory pain models. In addition, CT-044 has a favorable oral disposition and a clean toxicology profile in a broad variety of assays. This motivates us to pursue a direct-to-phase-II proposal to conduct GLP toxicology studies to enable an IND application to the FDA to move this asset toward the clinic for trials for post-surgical pain. We believe, based upon our experience, that the CT-044 data package exceeds, and that the data favorably compares to, even the most rigorous criteria posed by pharma houses that have successfully advanced analgesics to market. The majority of the proposed work constitutes dose escalation in order to set early human dose ranges, and conducting (essentially repeating) toxicological studies under GLP, and lastly, manufacturing CT-044 under GMP. Collectively this is a rare opportunity to advance a novel therapeutic class into humans with a high probability for success due to extensive preclinical de-risking studies. 1
Public Health Relevance Statement: PROJECT NARRATIVE & PUBLIC HEALTH RELEVANCE The development of non-opioid analgesics for the control of post-surgical pain is widely acknowledged as a critical need. Side effects of opioids include respiratory depression, sedation, nausea, constipation, sleep impairment, and a high potential for abuse and addiction. CERSCI Therapeutics is developing an orally- bioavailable small molecule peroxynitrite decomposition catalyst for the treatment of post-surgical pain. Our extensive preclinical work on this compound offers compelling evidence of the potential for safe, robust, and long-lasting analgesia. This Direct-to-Phase II project will generate data to support IND-enablement and will allow our lead compound, CT-044, to enter human clinical trials for post-surgical pain. 1
Project Terms: Absence of pain sensation; active control; Acute Pain; addiction; Adverse effects; Affect; Afferent Neurons; Age; American; Ames Assay; Analgesics; analog; Arachidonic Acids; arm; base; Bioavailable; Biological Assay; Biological Availability; Canis familiaris; Capsaicin; Cardiac; Cardiovascular Physiology; catalyst; Cause of Death; Centers for Disease Control and Prevention (U.S.); Chemicals; Clinic; Clinical Data; Clinical Research; Clinical Trials; Comorbidity; Constipation; cost; Country; Cyclooxygenase Inhibitors; Data; Depression and Suicide; Development; Diabetes Mellitus; disorder prevention; dosage; Dose; Double-Blind Method; efficacy trial; Enzymes; experience; Fentanyl; Free Radicals; Gated Ion Channel; Goals; Health Care Costs; Health Personnel; Healthcare Systems; healthy volunteer; Heart Diseases; Human; Impairment; In Vitro; in vivo; Industrialization; inflammatory pain; innovation; Investigational Drugs; Investigational New Drug Application; Ion Channel; Ion Channel Gating; Laparoscopic Cholecystectomy; Lead; Legal patent; Ligands; Malignant Neoplasms; Medicine; Metals; Micronucleus Tests; middle age; Minor; Modeling; Morphine; mouse model; Movement; Mutation; Nausea; Nervous system structure; Nitrogen; Nociception; Non-Steroidal Anti-Inflammatory Agents; novel; novel drug class; novel strategies; novel therapeutics; Operative Surgical Procedures; Opioid; Opioid Receptor; opioid use; Oral; Overdose; Oxygen; Pain; Pain management; painful neuropathy; Patients; Pattern; Peripheral Nervous System; Peroxonitrite; Pharmaceutical Preparations; Pharmacology; Phase; Placebo Control; Population; Postoperative Pain; pre-clinical; prescription opioid; prevent; Probability; Procedures; Production; Productivity; Property; Protein Isoforms; public health relevance; Randomized; Rattus; Respiratory physiology; response; Risk; Rodent; Safety; Schedule; Science; Sedation procedure; Series; Signal Transduction; Site; Sleep; small molecule; Societies; Structural Chromosomal Abnormality; Structure; success; Surgical incisions; Testing; Therapeutic; third molar extraction; Toxic effect; Toxicogenetics; Toxicology; Treatment Cost; Ventilatory Depression; voltage; Work; X ray diffraction analysis; X-Ray Diffraction
