A novel TRP modulator YB-2 to fight opioid crisis and treat chronic pain

Abstract There aremillion people living with chronic pain in the U Swhich is more than the combined prevalence of cancerdiabetes and heart diseaseChronic pain is the number one cause of long term disability in the U STo make matters worsethe prolific use of opioids to treat chronic pain has exacerbated drug abuse and addictionplacing opioid painkillers at the heart of a raging crisis that tookAmerican lives inTo curb the opioid crisisthe president declared a public health emergency while state lawmakers and various health systems started putting measures in place to cap the number of opioids prescribed by doctorsAlthough these measures have coincided withreductions in opioid prescriptions in recent yearsthis leaves Americans suffering from chronic pain with few if any effective optionThere is a significant and urgent need of alternative pain treatmentCapsaicin is a plant derived spice and medicine that has been formulated as an analgesic in topical ointments and dermal patches to relieve painThe therapeutic effect is achieved by targeting the transient receptor potential vanilloidTRPVthereby inactivating neurological pathways that transmit pain signalsDespite the promissory medicinal potentialthe inherent pungency and hydrophobicity severely restrict the effectiveness and application of capsaicin as an analgesic drugIt is of great importance to test the hypothesis that the TRPVactivity of capsaicin can be separated from the pungency and hydrophobicityBuilding on our core expertise in synthesizing and improving bioactive natural products as drug candidatesYoung BioPharma is dedicated to fighting the opioid crisis by developing safe and efficaciousnature product based therapies for the treatment of chronic painThrough our medicinal chemistry effortwe rectified the wrong SAR conclusions from the literature reportsconfirmed the hypothesis and discovered a novel compound YBwith potent in vitro TRPVmodulatory activitylow pungency and high aqueous solubilityWe believe this promising agent is an ideal candidate for further developmentInstead of being confined by inefficient topical use at low concentration like capsaicin due to pungency and hydrophobicityYBcan be employed at much higher dose in clinical trials through more effective i vand oral administrationsThusit will be much easier to achieve therapeutic endpointsWith a favorable therapeutic profileYBopens up a brand new paradigm as a potential game changing analgesic therapyproviding millions of patients with alternative safe and efficacious pain treatmentThe overall objective of this proposal is to develop novel TRP modulator YBto fight opioid crisis and treat chronic painIn order to advance this therapeutic towards the IND application with the FDAwithinmonths we aim to synthesizeg of YBconfirm the in vitro activitytest YBin three animal models of pain via i vand oral administrationsand conduct DMPK studiesWe consider phase I successful if YBcan demonstrate in vivo efficacy in at leastof theanimal models without significant side effect Public health narrative There aremillion people living with chronic pain in the U Swhich is more than the combined prevalence of cancerdiabetes and heart diseaseTo make matters worsethe prolific use of opioids to treat chronic pain has exacerbated drug abuse and addictionplacing opioid painkillers at the heart of a raging crisisWe are dedicated to fighting the opioid crisis by developing a novel TRP modulator YBas a potential game changing analgesic therapythus providing millions of patients with alternative safe and efficacious pain treatment