Nocion Therapeutics was founded based on research from Clifford Woolf and Bruce Bean from HMS, together with Bruce Levy, head of respiratory at BWH. Clifford is an expert in pain, and Bruce Bean is an electrophysiologist. The founders came up with an idea to enhance the efficacy of lidocaine while reducing its side effects, such as numbness. Lidocaine and other related anesthetics block sodium channels and large pore channels directly. Nocion’s molecules are designed to enter the cell through large pore channels where they become trapped inside the cell and act to block all sodium channels for an extended duration compared to lidocaine. The large pore channels are only open when there is inflammation, so Nocion’s inhibitors offer selective and sustained blockage of inflamed neurons. Nocion has shown that activation of the nervous system impacts inflammation, so there is a feedback loop that then results in further inflammation and nervous system activation. Nocion molecules should interrupt this loop and lead to a reduction in inflammatory disorders.
With Bruce Levy’s guidance, Nocion selected chronic cough as their lead program. Chronic cough is a huge unmet need, where patients often cough up to 50 times per minute. It is often the first reason patients will visit a doctor, and currently, the only treatment is opioid drugs that carry significant and well-recognized liabilities. Recently, a cough monitoring instrument was developed in the UK called VitaloJAK, which enables objective measurement of clinical endpoints for cough suppression. Afferent, a venture-backed startup developing an oral medication for cough, used this clinical outcome monitor and was acquired by Merck for $500M upfront (with up to $750M in success milestones). While nonopioid efforts exist, such as sodium channel inhibitors, none have been successful to date. Unfortunately, despite significant industry efforts, neither small molecule or antibody drugs against sodium channels (such as Nav1.7, Nav1.8, or Nav1.9) have yet proven effective. Efforts, particularly to selectively target Nav1.8 and Nav1.9, are ongoing. Prior to company formation, the founders approached B-BIC, the Boston Biomedical Innovation Center, for a grant which enabled further testing of hits in a guinea pig model, selected because it best represented how human patients present cough. B-BIC ensured that multiple compounds of varying potency and chemical structure were tested in vitro and in vivo, and thereby forged a strong in vitro/in vivo link. Thanks in part to B-BIC’s funding which led to a strong in vivo translational data package, Nocion was able to attract a top tier VC syndicate including PIF, F-Prime and Canaan Partners for a $27M Series A. Nocion has also leveraged PIF’s network to engage leading KOLs in various therapeutic areas such as women’s health, pain and dermatology as they seek to expand the clinical indications for their molecules.
With their Series A funding in the bank, Nocion is moving rapidly to recruit a first-rate R&D team and strong executive leadership. Their lead product should enter the clinic for chronic cough next year using inhaled delivery. Nocion expects to have data in patients in early 2021. Nocion has also expanded their chemistry platform and is considering topical delivery of molecules for pain and itch or local delivery for esophagitis and irritable bowel syndrome.
As Meredith Fisher, PIF Partner and board member notes, “we were excited about Nocion the first time we heard about it from the founders years ago. It represents the combination of a well-defined biological mechanism with a clever chemical approach. The founding team generated a strong translational data package validating the therapeutic intervention strategy which then attracted ventureinterest. We are thrilled at the progress the company has made in such a short amount of time and theclinical potential for Bruce, Clifford, and Bruce’s research in an area of significant unmet need.”