Karuna Announces First Patient Dosed in Phase 2 Study of Lead Product Candidate KarXT for the Treatment of Schizophrenia

Phase 2 study aims to reproduce significant efficacy previously
observed in schizophrenia trial with xanomeline alone

Company also announces successful Phase 1 study of proprietary
xanomeline and trospium chloride co-formulation, which will be used in
Phase 2 study

BOSTON–(BUSINESS WIRE)–Karuna
Pharmaceuticals, Inc.
(“Karuna”), focused on targeting muscarinic
cholinergic receptors for the treatment of neuropsychiatric disorders
marked by psychosis and cognitive impairment, today announced the
initiation of a Phase 2 study evaluating the efficacy and safety of its
lead product candidate, KarXT (Karuna-Xanomeline-Trospium), for the
treatment of psychosis in schizophrenia. The study will use a
co-formulation of KarXT, which was well-tolerated at dose levels
exceeding those shown to be efficacious in previous xanomeline studies.
Top-line data results from the Phase 2 study are expected at the end of
2019.

“We are excited to progress our development of KarXT, which has the
potential to be the first antipsychotic drug with a unique mechanism in
over 60 years and one which could be effective in treating not only
positive symptoms but also the disabling negative and cognitive symptoms
of the disease. Our Phase 2 study uses the same fundamental design as
the successful efficacy study conducted previously with xanomeline
alone,” said Steve Paul, M.D., Chief Executive Officer of Karuna. “We
have designed KarXT as a novel approach to reduce the cholinergic sides
effects related to the activation of peripheral muscarinic receptors
that were observed in previous studies by Eli Lilly. We have now
demonstrated the improved tolerability in two Phase 1 studies, including
with the proprietary co-formulation of xanomeline and trospium.”

Karuna’s KarXT was evaluated in a Phase 1 dose-ranging study that
enrolled 70 healthy volunteers and successfully demonstrated
tolerability at dose levels exceeding those shown to be efficacious in
previous studies of xanomeline alone. The co-formulation also achieved
exposure levels equivalent to or higher than the separate dosage forms
used previously, and the results supported dose selection to be carried
forward into Phase 2. There were no severe or serious adverse events
reported in the co-formulation study. Side effects associated with KarXT
were mild-to-moderate and transient in nature, often only lasting a few
hours, and they were consistent with the previous KarXT study that used
separate dosage forms for xanomeline and trospium.

The Phase 2 study is a double-blind, placebo-controlled study designed
to evaluate the efficacy and safety of KarXT in approximately 160
patients with schizophrenia. The primary endpoint is total change from
baseline Positive and Negative Syndrome Scale (PANSS) score compared to
placebo. Additional endpoints will assess cognitive and negative
symptoms in addition to general symptomology. The study employs a
flexible dose design where patients are randomized in a 1:1 ratio to
receive either KarXT or placebo for 5 weeks. Patients assigned to the
KarXT arm will be treated with 100/20 mg xanomeline/trospium with the
option to increase the dose to 125 mg/30mg xanomeline/trospium after the
first week of the study.

About Schizophrenia

Schizophrenia affects more than 20 million people worldwide and is
characterized by profound disruptions to daily life. Symptoms are
grouped within three domains: positive, negative, and cognitive.
Positive symptoms are generally associated with psychotic behaviors,
including hallucinations and delusions. Negative symptoms refer to
disruptions in behavior and emotions and can manifest as reduced social
engagement and motivation. Cognitive symptoms are marked by changes in
memory and attention. The prognosis for schizophrenia remains poor as
only 30 percent of patients live independently and only 10 to 20 percent
maintain full-time employment. There is a desperate need for new
treatments in schizophrenia that not only address positive, negative,
and cognitive symptoms of the disease, but are also safer than existing
medicines.

About KarXT

KarXT
(Karuna-Xanomeline-Trospium) is Karuna’s lead investigational product
candidate for the treatment of psychosis in schizophrenia. It consists
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 central nervous system (CNS). KarXT is
designed to selectively target M1/M4 muscarinic receptors in the brain
while blocking their activation in peripheral tissues to significantly
improve tolerability. Results from a Phase 1 study demonstrating the
improved tolerability of KarXT vs. xanomeline alone were announced in
2016, and a more recent Phase 1 study completed in 2018 supported the
development of a co-formulation of KarXT that is now being evaluated in
a Phase 2 study.

About Karuna Pharmaceuticals

Karuna is a clinical-stage drug development company targeting muscarinic
cholinergic receptors for the treatment of psychosis and cognitive
impairment across central nervous system (CNS) disorders, including
schizophrenia and Alzheimer’s disease, as well as pain. Karuna’s lead
product candidate, KarXT
(Karuna-Xanomeline-Trospium), is being evaluated in a Phase 2 study in
people with schizophrenia, with top-line results anticipated at the end
of 2019. Karuna, which was founded by PureTech
Health
 (LSE: PRTC), has a worldwide exclusive license for xanomeline
and has an intellectual property portfolio more broadly covering
selective muscarinic targeting enabled by the KarXT approach. For more
information, visit www.karunapharma.com.

Forward Looking Statement

This press release contains statements that are or may be
forward-looking statements, including statements that relate to the
company’s future prospects, developments and strategies. The
forward-looking statements are based on current expectations and are
subject to known and unknown risks and uncertainties that could cause
actual results, performance and achievements to differ materially from
current expectations, including, but not limited to, those risks and
uncertainties described in the risk factors included in the regulatory
filings for PureTech Health plc. These forward-looking statements are
based on assumptions regarding the present and future business
strategies of the company and the environment in which it will operate
in the future. Each forward-looking statement speaks only as at the date
of this press release. Except as required by law and regulatory
requirements, neither the company nor any other party intends to update
or revise these forward-looking statements, whether as a result of new
information, future events or otherwise.

Contacts

Karuna Pharmaceuticals, Inc.
Investors
Allison Mead
Talbot, +1 617-651-3156
amt@puretechhealth.com
or
U.S.
media

Tom Donovan, +1 857-559-3397
tom@tenbridgecommunications.com