SITEONE THERAPEUTICS, INC. — Department of Health and Human Services SBIR Phase II: 108

Description

PROJECT SUMMARY This program aims to develop a novel non opioid therapeutic for the treatment of pain that targets a subtype of the human voltage gated Na ion channel NaV Preliminary data indicate that SiteOneandapos s lead drug candidates may be more effective than opioids for treating certain types of pain and lack the side effects associated with opioid analgesics which include nausea drowsiness respiratory depression and potential for addiction Voltage gated Na ion channels are integral membrane proteins responsible for the transmission of signals along electrically conducting cells Ten mammalian genes have been sequenced which encode ten distinct channel isoforms NaV and NaX each having unique gating properties and cellular and tissue distribution patterns Recent studies have correlated a hereditary loss of function mutation in one human Na channel isoform NaV with a rare genetic disorder known as Congenital Insensitivity to Pain CIP Individuals with CIP have reduced sensitivity to normally painful stimuli without significant deficits to sensory or cognitive function A compelling body of evidence indicates that selective inhibition of NaV in normal humans could recapitulate the phenotype of CIP However the high homology of human NaV proteins coupled with challenges associated with high throughput screening against multiple ion channel targets have thwarted most efforts to develop selective antagonists for individual NaV subtypes SiteOne has identified a small collection of drug candidates that exhibit to fold selectivity for inhibition of human NaV over other peripheral human NaV isoforms During Phase I and Phase II of our program lead drug candidates were discovered by leveraging a two amino acid variation in the pore region of NaV that is not present in any other human NaV isoform These compounds have been advanced through a series of in vitro and in vivo pharmacology pharmacokinetic safety and efficacy studies During Phase IIB of our program we aim to improve the synthetic route to a single lead drug candidate manufacture multi hundred gram quantities of this compound and complete characterization pharmacology and safety studies in support of an Investigational New Drug application Success of this program will lead to the filing of an IND and support advancement of a novel selective inhibitor of NaV into clinical testing PROJECT NARRATIVE Existing paradigms for pain treatment rely heavily on opioid analgesics such as morphine oxycodone and fentanyl which are not effective for treating all types of pain and are associated with a range of side effects including nausea drowsiness respiratory depression and potential for addiction Our program aims to develop a non opioid pain therapy which is effective for treating opioid resistant and or breakthrough pain and specifically targets pain signals without affecting cognition Such a therapy is expected to show improved efficacy and significantly fewer milder side effects than existing drugs