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Concert Pharmaceuticals Initiates Phase 1 Multiple-Ascending Dose Trial of CTP-692 as an Adjunctive Treatment for Schizophrenia

April 10, 2019 Off By BusinessWire

LEXINGTON, Mass.–(BUSINESS WIRE)–lt;a href="https://twitter.com/search?q=%24CNCE&src=ctag" target="_blank"gt;$CNCElt;/agt; lt;a href="https://twitter.com/hashtag/CNCE?src=hash" target="_blank"gt;#CNCElt;/agt;–Concert
Pharmaceuticals, Inc. (NASDAQ: CNCE) today announced that it has
initiated an additional trial in the Phase 1 program evaluating CTP-692,
a novel deuterium-modified form of D-serine being developed as an
adjunctive treatment for schizophrenia. The Phase 1 multiple-ascending
dose trial will evaluate the safety, tolerability, and pharmacokinetic
profile of CTP-692 in healthy volunteers. Topline data from both the
single-and multiple-ascending CTP-692 Phase 1 trials are expected in the
second quarter of 2019.

“The Phase 1 studies evaluating the dosing and safety of CTP-692 are
expected to support advancement into an efficacy study in patients with
schizophrenia later this year. D-serine is an important endogenous
co-agonist of the NMDA receptor in humans which has been shown to be
present at lower levels in the blood and cerebrospinal fluid in
individuals with schizophrenia. We are pleased with CTP-692’s
pharmacokinetic and safety profile to date and believe that it has the
potential to offer a safe and effective agent to enhance NMDA function,
providing a new approach to treating symptoms of schizophrenia,” said
Roger Tung, Ph.D., President and Chief Executive Officer of Concert
Pharmaceuticals. “CTP-692 represents the fastest moving program in our
pipeline to date, demonstrating our team’s ability to rapidly identify
and pursue compelling new therapeutic opportunities based on Concert’s
deuterium chemistry platform.”

The Phase 1 program is designed to assess CTP-692’s safety, tolerability
and pharmacokinetics in approximately 80 healthy volunteers. The Phase 1
program includes three studies: a crossover comparison of CTP-692 versus
D-serine, a single-ascending dose study that also assessed the effect of
food on the pharmacokinetics of CTP-692, and the multiple-ascending dose
trial announced today. This trial is a double-blind, placebo-controlled,
multiple-ascending dose trial assessing CTP-692 dosed orally over seven
days. In individuals treated in the crossover study with both CTP-692
and D-serine, CTP-692 was found to have increased plasma exposure
compared to D-serine. In addition, CTP-692 was found to be well
tolerated in healthy volunteers and no serious adverse events were
reported.

The CTP-692 clinical program is supported by results from Concert’s
preclinical studies which have shown the potential of CTP-692 to improve
upon the safety profile of D-serine. D-Serine has been shown to cause
nephrotoxicity in published preclinical studies. Concert’s preclinical
studies have demonstrated that selective deuterium modification resulted
in increased exposure of CTP-692 relative to a similar dose of D-serine,
and administration of CTP-692 did not cause changes in serum creatinine
and blood urea nitrogen at doses where D-serine caused substantial
nephrotoxicity as assessed by these kidney function markers. These
preclinical results were presented by Concert at the American College of
Toxicology 2018 Annual Meeting in November 2018. A copy of the poster
may be accessed in the Scientific Presentations section of the Company’s
website at www.concertpharma.com.

About CTP-692

CTP-692 is a deuterium-modified analog of endogenous D-serine. Based on
documented effects of D-serine, the Company believes that CTP-692 has
the potential to restore NMDA receptor activity in key areas of the
brain and improve clinical outcomes in patients with schizophrenia.
CTP-692 has been shown to have similar ability to bind to and activate
human NMDA receptors relative to D-serine, with the potential for an
improved safety profile and improved clinical outcomes in the treatment
of schizophrenia. CTP-692 will be developed as an adjunctive therapy
administered in addition to standard antipsychotic medicines to improve
both positive and negative symptoms as well as cognitive function in
patients with schizophrenia.

An extensive body of evidence supports NMDA receptor hypofunction as a
key underlying mechanism of schizophrenia. The NMDA receptor comprises
two binding domains and, in addition to requiring glutamate binding,
activation with a co-agonist such as D-serine or glycine is necessary
for NMDA receptor activation. D-Serine is believed to be the most
important human NMDA synaptic co-agonist. It has been postulated for
some time that administration of NMDA co-agonists could benefit patients
with schizophrenia since there is evidence that plasma and cerebrospinal
fluid (CSF) levels of endogenous D-serine are reduced in patients with
schizophrenia.

About Schizophrenia

Schizophrenia is a chronic and devastating neuropsychiatric disorder
that is ranked as a leading cause of disability worldwide. The disease
afflicts nearly 1% of the world’s population, affecting both men and
women equally, and striking all ethnic and socioeconomic groups with
similar prevalence. The illness is characterized by multiple symptoms
that are categorized into three main clusters known as positive symptoms
(hallucinations, delusional behaviors and thought disorder), negative
symptoms (social withdrawal, flattened affect and poverty of speech),
and cognitive dysfunction (diminished capacity for attention, working
memory and executive function). The underlying basis of the current
antipsychotic therapy is that excessive dopaminergic neurotransmission
and dysfunctional D2 receptor signaling play key pathophysiological
roles in the disease, and consequently all typical and atypical
antipsychotics in clinical practice possess some level of D2 antagonist
activity. Currently available antipsychotic drugs offer some benefit for
positive symptoms but many patients are not adequately treated since
currently available treatments are limited in their capacity to treat
negative symptoms and cognitive dysfunction which are related to poor
functional outcomes.

About Concert

Concert
Pharmaceuticals is a clinical stage biopharmaceutical company
focused on applying its DCE
Platform® (deuterated chemical entity platform) to create novel
medicines designed to treat serious diseases and address unmet patient
needs. The Company’s approach starts with previously studied compounds,
including approved drugs, in which deuterium substitution has the
potential to enhance clinical safety, tolerability or efficacy.
Concert’s pipeline of
innovative medicines currently targets autoimmune diseases and central
nervous systems (CNS) disorders. For more information please visit www.concertpharma.com
or follow us on Twitter at @ConcertPharma
or on LinkedIn.

Cautionary Note on Forward Looking Statements

Any statements in this press release about our future expectations,
plans and prospects, including statements about the clinical development
of CTP-692 and other statements containing the words “anticipate,”
“believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,”
“plan,” “potential,” “predict,” “project,” “should,” “target,” “would,”
and similar expressions, constitute forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by such
forward-looking statements as a result of various important factors,
including: the uncertainties inherent in the initiation of future
clinical trials, availability and timing of data from ongoing and future
clinical trials and the results of such trials, whether preliminary
results from a clinical trial will be predictive of the final results of
that trial or whether results of early clinical trials will be
indicative of the results of later clinical trials, expectations for
regulatory approvals and other factors discussed in the “Risk Factors”
section of our most recent Annual Report on Form 10-K filed with the
Securities and Exchange Commission and in other filings that we make
with the Securities and Exchange Commission. In addition, any
forward-looking statements included in this press release represent our
views only as of the date of this release and should not be relied upon
as representing our views as of any subsequent date. We specifically
disclaim any obligation to update any forward-looking statements
included in this press release.