12 September 2016
PureTech Health plc
PureTech's Karuna Doses First Subject in Tolerability Proof-of-Concept Study of Lead Product Candidate
PureTech Health plc ("PureTech", LSE: PRTC), a cross-disciplinary biotech company developing 21st century medicines in and at the interface of the immune, central nervous and gastro-intestinal systems, is pleased to note that Karuna Pharmaceuticals today announced the dosing of the first subject in a tolerability proof-of-concept study for its proprietary lead product. The study, which will be conducted in up to 70 healthy individuals, aims to evaluate the tolerability of KarXT (xanomeline plus trospium chloride) compared to xanomeline alone. 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. By selectively targeting muscarinic receptors in the central nervous system with the KarXT approach, Karuna aims to advance xanomeline, which is exclusively licensed to Karuna, as a potential novel treatment option for patients.
Daphne Zohar, Co-Founder and Chief Executive Officer at PureTech, said: "There is a significant unmet need for treatments that can efficaciously and safely manage schizophrenia and Alzheimer's disease. We hope to offer a solution to patients afflicted by these diseases."
The full text of the announcement from Karuna Pharmaceuticals is as follows:
Karuna Doses First Subject in Tolerability Proof-of-Concept Study of Lead Product Candidate
BOSTON, Massachusetts, September 12, 2016 -- 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.
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. For more information, visit www.karunapharma.com.
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. For more information, visit www.puretechhealth.com and connect with us on Twitter.
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Allison Mead, Director, Communications and Investor Relations
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FTI Consulting (Communications adviser to PureTech)
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