OREANDA-NEWS. Karuna Pharmaceuticals, a company focused on targeting muscarinic receptors for the treatment of central nervous system (CNS) disorders including schizophrenia and Alzheimer's disease, today announced the dosing of the first subject in a tolerability proof-of-concept study of its proprietary lead product KarXT (xanomeline plus trospium chloride). The study, which will be conducted in up to 70 healthy individuals, aims to evaluate the tolerability of KarXT compared to xanomeline alone.  

Exclusively licensed to Karuna, xanomeline is a novel, muscarinic acetylcholine receptor agonist that has demonstrated robust efficacy in treating schizophrenia and psychosis in Alzheimer's disease; however, it has also been associated with tolerability issues that have hindered its development. In a double-blind, placebo-controlled, monotherapy study in people with schizophrenia, a statistically significant, 24-point reduction over placebo was observed on the Positive and Negative Syndrome Scale (PANSS), a standard tool used to measure symptom severity in people with schizophrenia. By selectively targeting muscarinic receptors in the CNS with the KarXT approach, Karuna aims to reduce the peripheral cholinergic side effects previously seen with xanomeline alone. 

"In clinical studies, xanomeline has shown robust efficacy in people with schizophrenia and in people with Alzheimer's disease, demonstrating the immense potential of targeting the M1/M4 muscarinic acetylcholine receptors; however, the muscarinic field has been stymied by tolerability concerns caused by activation of muscarinic receptors in peripheral tissues," said Andrew Miller, Ph.D., Karuna's Chief Executive Officer. "By combining xanomeline with trospium chloride, we aim to unlock the therapeutic potential of M1/M4 agonists and address the significant unmet need in treating these disorders." 

The randomised, double-blind, multiple-dose study will dose up to 70 healthy volunteers aged 18 to 60 for in-clinic treatment over the course of nine days. Following a two-day run-in period with trospium alone, subjects will receive xanomeline with either trospium chloride or placebo. Top-line results are expected by the end of 2016. 

About Karuna

Karuna is a clinical-stage drug development company targeting muscarinic receptors for the treatment of central nervous system (CNS) disorders. Karuna's lead program, KarXT, is a product candidate consisting of xanomeline, a novel muscarinic acetylcholine receptor agonist that has demonstrated efficacy in placebo-controlled human trials in schizophrenia and Alzheimer's disease, and trospium chloride, an FDA-approved and well-established muscarinic receptor antagonist that has been shown not to enter the CNS. 

Schizophrenia is a severe and chronic mental health disorder that affects more than 21 million people worldwide. The disease is characterized by profound disruptions in thinking, affecting language, perception and the sense of self, and it typically includes psychotic episodes. Antipsychotics are the mainstay therapy for the treatment of schizophrenia; however, significant unmet needs remain due to the limited efficacy and potential serious side effects associated with current antipsychotic medications.  

Alzheimer's disease is a chronic, progressive, neurodegenerative disorder characterized by loss of memory and other important mental functions. The type, severity, sequence and progression of mental changes vary widely, and it represents an enormous burden on victims of the disease and their families. Alzheimer's is the most common form of dementia in people over the age of 65, and it is estimated to affect more than 5 million Americans. It is the sixth leading cause of death in the United States, and there is currently no cure. 

Karuna's Board of Directors includes Ben Shapiro, M.D., former Executive Vice President of Research for Merck & PureTech Health Non-Executive Director; Edmund Harrigan, M.D., former Senior Vice President for Worldwide Safety and Regulatory, Head of Worldwide Business Development at Pfizer; and Atul Pande, M.D., Former Senior Vice President, Head of Neuroscience and Senior Advisor, Pharmaceutical R&D at GlaxoSmithKline & PureTech Health Senior Advisor. Karuna's Chief Clinical Advisor is Alan Breier, M.D., the former Chief Medical Officer at Eli Lilly. Karuna has a worldwide exclusive license for xanomeline and has a patent portfolio more broadly covering selective muscarinic targeting enabled by the KarXT approach.

PureTech Health plc (PRTC.L) owns 79.6% of the company on a diluted basis plus potential product royalties as of 30 June 2016. This calculation includes issued and outstanding shares as well as options to purchase shares and written commitments to issue shares or options, but excludes unallocated shares authorised to be issued pursuant to equity incentive plans. 

About PureTech Health

PureTech Health (PureTech Health plc, PRTC.L) is a cross-disciplinary biotech company focused on areas of growing scientific and technical insights that it believes are at an important inflection point, including the immune, central nervous and gastro-intestinal systems, and the interactions and signalling between them. PureTech has more than 20 clinical studies across its pipeline targeting multibillion-dollar market opportunities, including five human proof-of-concept studies and multiple pivotal or registration study readouts expected in the next two years. While inevitably some technologies will not advance to commercialisation, PureTech's approach mitigates risk as most of the cash resides on a PureTech parent company level, allowing PureTech to build value and divert cash to its most successful programmes as milestones are achieved. PureTech has over 220 patents and patent applications. PureTech's leading team and board, along with an advisory network of more than 70 expert founder-scientists and advisors across multiple disciplines, gives PureTech access to potentially ground-breaking science and technological innovation. With healthcare undergoing major transformation, PureTech believes it is well positioned to develop and launch medicines for the 21st century.