Karuna Pharmaceuticals - First Subject in Tolerability Proof-of-Concept Study of Lead Product Candidate

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 randomized, 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.

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Background on the company:

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Karuna Pharmaceuticals targeting schizophrenia with new discoveries licensed from Vanderbilt University

Boston-based Karuna Pharmaceuticals is set to announce this week that it has licensed a set of scientific discoveries from Vanderbilt University’s Center for Neuroscience Discovery. The start-up hopes to develop them into effective new drugs for schizophrenia, a disabling mental illness that affects more than 24 million people worldwide.
A problem with existing drugs for schizophrenia, explains Karuna chief executive Ed Harrigan, is that they only treat some of the symptoms of the disease. “Current drugs do a reasonable job with hallucinations and delusions. But they don’t address some of the impairments of attention and memory, or the asociality and anhedonia that can accompany the disease. And those are all symptoms that can really block people from being reintegrated into society.”

Karuna is developing a treatment for schizophrenia, based on a drug that is no longer patented. (The company has made modifications and applied for a new patent.) Harrigan, formerly a senior licensing executive at Pfizer, says both programs “have the potential to be a breakthrough treatment.” The off-patent drug has already been through clinical trials, and Karuna may soon begin trials of its own.

More information on this company here:

http://www.karunapharma.com/

A pretty impressive team is listed - I hope they are strongly engaged in this company’s efforts (and not just names on a website):

http://www.karunapharma.com/our-team/

I looks like the company has been active for about 5 years or so - here is some past news on it:

The former chief of licensing for the drug giant Pfizer has stepped in as CEO of Karuna Pharmaceuticals, a stealthy Boston startup focused on new treatments for schizophrenia. Ed Harrigan tells me that he started the job at Karuna this month.

Karuna has two novel programs in development for the treatment of schizophrenia, Harrigan says. Karuna has been incubating at the Boston firm PureTech Ventures, whose partner Eric Elenko had been in charge of day-to-day operations before Harrigan took over those duties. Karuna’s founding team also includes PureTech associate Andrew Miller.

Both Elenko and Harrigan declined to reveal any specifics about the science at the startup, yet they did mention that one of the firm’s molecules with a novel mechanism for treating schizophrenia is being tested in humans. Schizophrenia, which affects about 2.4 million American adults, is a mental disorder that impacts people’s ability to tell what is real and not real.

Harrigan, 57, is a neurologist by training whose name gives Karuna lots of credibility in the pharmaceutical world. Before he left Pfizer (NYSE: PFE) in March 2010, Harrigan led the $1 billion deal between the company and Bristol-Myers Squibb (NYSE: BMY) that brought Pfizer commercial rights to Bristol-Myers’s blood thinner apixaban. The companies are seeking FDA approval of apixaban, which could be a blockbuster drug for the firms. Earlier in his career at Pfizer, Harrigan also played a key role in the development of the antipsychotic pill ziprasidone (Geodon).

Strangely - it looks like they only raised $600K in funding initially and a few million more in awards/grands - they’ll need a lot more:

Aug. 5, 2015 Karuna Pharmaceuticals, Inc. (“Karuna”), a PureTech (PureTech Health plc PRTC.L) company developing a novel product candidate for the treatment of schizophrenia, announced today that it has received a Translation Fund Award from the Wellcome Trust comprising an unsecured convertible loan to Karuna of up to $3.84 million. The funding, along with other capital, will be applied to further develop Karuna’s lead program KarXT, a potentially innovative therapy for the treatment of schizophrenia.

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Is it early to say its good for negative symptoms of Sz…!!!

These guys seem very cool!

These are all phase 1, it will take the greter part of a decade for these meds to come out.

That may be true but hopefully they will eventually help people. Better phase 1 now than 5 years down the line.

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