BOSTON–(BUSINESS WIRE)–Jun 19, 2018–Karuna Pharmaceuticals, an affiliate of PureTech Health plc (LSE: PRTC), focused on targeting muscarinic receptors for the treatment of disorders marked by psychosis and cognitive symptoms, today announced that it has been awarded approximately $8 million by the Wellcome Trust. The funding will be used to further advance clinical development of Karuna’s lead program, KarXT (Karuna-Xanomeline-Trospium), through a Phase 2 study in people with schizophrenia.
“Antipsychotics are the mainstay therapy for the treatment of schizophrenia and have all relied on the same fundamental mechanism of action for the past 60 years. Currently available treatments have limited efficacy – primarily addressing only positive symptoms, such as hallucinations and delusions – and are often associated with serious, often irreversible, side effects, leaving a significant need for new treatments for people living with this devastating disease,” said Andrew Miller, Ph.D., President and Chief Executive Officer of Karuna. “With KarXT, we have an opportunity to potentially improve positive, negative, and cognitive symptoms based on prior compelling efficacy data with xanomeline, and without the debilitating side effects of existing therapies. We are delighted that Wellcome is continuing to back this important new therapeutic approach.”
"Karuna Pharmaceutical’s lead program, KarXT, is a clinical stage program targeting the muscarinic acetylcholine receptors composed of xanomeline, a novel muscarinic acetylcholine receptor agonist (activator) and trospium chloride, an FDA-approved and well-established muscarinic receptor antagonist (blocker) that has been shown not to enter the central nervous system.
The muscarinic receptors in the nervous system bind to acetylcholine (a neurotransmitter). There are five types of muscarinic receptors (M1-M5), all of which are expressed in the brain, with the M2 and M3 receptors also significantly expressed in the periphery outside the brain (e.g., in sweat glands, salivary glands and the GI tract). Activation of muscarinic receptors outside of the brain is associated with side effects (e.g. GI adverse events). The muscarinic system has long been of interested for drug development, however, side effects associated with activation of peripheral muscarinic receptors has not allowed any medicine to reach the market. KarXT is a novel approach designed specifically to overcome this fundamental roadblock and unlock the potential of muscarinic agonists that has yet to be realized. Karuna’s first clinical trial demonstrated the proof-of-concept for the KarXT approach by showing that trospium could significantly improve the tolerability profile of xanomeline in healthy volunteers, enabling further development. "
