40 mg dose showed statistically significant improvement on Cogscreen objective cognitive measures of
attention and memory
Two additional self-rated secondary endpoints (CPFQ and QIDS) showed statistically significant
improvements in depressive symptoms with procognitive benefits, reinforcing the benefit with SDQ endpoint reported
previously
NSI-189 appeared to be safe and well tolerated with no serious adverse events
The Company will be hosting a conference call today, Tuesday, December 5th at 8:30 a.m.
ET
GERMANTOWN, Md., Dec. 05, 2017 (GLOBE NEWSWIRE) -- Neuralstem, Inc. (Nasdaq:CUR), a biopharmaceutical company developing novel
treatments for nervous system diseases, today announced that additional safety, efficacy and tolerability data from its exploratory
Phase 2 clinical trial examining the efficacy of NSI-189 at 40 mg once daily (QD) and 40 mg twice daily (BID) compared to placebo
for the treatment of major depressive disorder (MDD) were presented at the 56th American College of Neuropsychopharmacology (ACNP)
Annual Meeting in a poster entitled, “A Phase 2, Double-Blind, Placebo-Controlled Study of NSI-189 Phosphate, a Neurogenic
Compound, Among Out-Patients with Major Depressive Disorder.” These additional results suggest that NSI-189 has
antidepressant effects with cognitive benefits shown on both objective and subjective measures.
“NSI-189 appears to be a broad-acting antidepressant, with effects in both core symptoms of depression and in aspects of
cognition where standard antidepressants typically show very modest effects. These results warrant the continued study of
this compound among MDD patients who are inadequately managed by current antidepressant therapies,” said Maurizio Fava, MD,
Director of the Division of Clinical Research of the MGH Research Institute and Executive Vice Chair, Department of Psychiatry at
Massachusetts General Hospital, and the principal investigator of the trial.
In the Phase 2 trial, 220 subjects were randomized to: NSI-189 40mg daily (n=44), NSI-189 80mg daily (n=44), or placebo (n=132)
for 6 weeks (Stage 1). At the end of 6 weeks, placebo-treated subjects who were non-responders (defined as less than 50% reduction
in Montgomery-Asberg Depression Rating Scale (MADRS)) with a MADRS score greater than 15 were re-randomized to 6 weeks treatment
with NSI-189 40 mg daily (n=22), NSI-189 80 mg daily (n=22), or placebo (n=22) (Stage 2). Patients on NSI-189 who completed
Stage 1 continued the same dose for another 6 weeks. The primary outcome measure was the MADRS. Secondary outcome
measures included the 17-item Hamilton Depression Rating (HAMD-17), the Symptoms of Depression Questionnaire (SDQ), the Cognitive
and Physical Functioning Scale (CPFQ), the patient-rated version of the Quick Inventory of Depressive Symptomatology Scale
(QIDS-SR), and CogScreen and CogState objective cognitive tests. Efficacy results concerning all patients randomized in Stage 1
were pooled (50:50 weighted average) with the Stage 2 results of all re-randomized patients who had been non-responders to placebo
in Stage 1.
Using the Sequential Parallel Comparison Design (SPCD) pooled analysis approach, MADRS score reduction from baseline with 40mg
or 80mg NSI-189 versus placebo did not reach statistical significance (mean difference -1.8, p=0.22, mean difference -1.4, p=0.34,
respectively). However, the 40 mg dose resulted in a statistically significant reduction in SDQ (mean difference -8.2,
p=0.04), and CPFQ scores (mean difference -1.9, p=0.03) versus placebo in the pooled SPCD analyses. There was also a statistically
greater reduction in QIDS-SR scores versus placebo for patients treated with 40 mg of NSI-189 in Stage 2 (-2.5, p=0.04), but not
Stage 1. Differences for the 80 mg dose versus placebo on these three self-report measures were not statistically
significant.
In addition, the 40mg dose also showed statistical advantages on objective measures of attention and memory as per the Cogscreen
test, but not the Cogstate test: Simple Attention (SATADRTC, p=0.034; Complex Attention (SATACACC, p = 0.048) and Memory
(SDCDRACC, p = 0.002; also seen with 80mg dose, p = 0.015).
Both doses were well-tolerated with 0, 0 and 7 subjects discontinuing treatment with 40mg, 80mg and placebo, respectively, due
to intolerance in Stage 1, and 1,0 and 1 subjects discontinuing treatment with 40mg, 80mg and placebo, respectively, due to
intolerance in Stage 2. Furthermore, no subjects treated with NSI-189 experienced a serious adverse event during the
study.
“We are extremely pleased that the novel, neurogenic, neurotrophic mechanism of action of NSI-189 has shown both antidepressant
and pro-cognitive activity in depressed patients, and which appears to result in meaningful benefit as reported both by the
patients themselves and by objective computerized measurements. These results further support those from the previous Phase
1b in subjects with MDD, which demonstrated potential efficacy on both depression and cognition scales. We look forward to meeting
with the Food and Drug Administration (FDA) in the first half of 2018 to further define the clinical development and regulatory
paths for NSI-189, as well as to submit the results of this study to a peer reviewed publication by the end of this year,” said
Rich Daly, Chairman and CEO, Neuralstem.
Conference Call and Webcast
In connection with this announcement, Neuralstem will host a conference call today, Tuesday, December 5, at 8:30 a.m. ET. The call
can be accessed by dialing 1 (833) 584-0034 (U.S. and Canada) or 1 (409) 350-3602 (international). The conference ID number is
4382159. To access the live webcast, or the subsequent archived recording, visit the "Events" section of the Neuralstem website at
www.neuralstem.com. An archived presentation will be available for 90 days.
About NSI-189
NSI-189, a benzylpiperazine-aminopyridine, is a small molecule in clinical development for MDD and in preclinical development
for Angelman syndrome, irradiation-induced cognitive impairment, Type 1 and Type 2 diabetes, and stroke. NSI-189 is a novel
compound developed for the treatment of MDD. Data suggest that NSI-189 works by promoting synaptogenesis or neurogenesis in the
hippocampus; a different mechanism of action than currently marketed antidepressants. Based on preclinical studies, NSI-189
has shown to stimulate neurogenesis of human hippocampus-derived neural stem cells in vitro and stimulates neurogenesis in mouse
hippocampus in vivo. These studies suggest that NSI-189 may have broad utility as a neuroregenerative drug. NSI-189 was
discovered using the Company’s stem cell-based screening platform. The Company’s portfolio of small molecule compounds, which
includes NSI-189, are covered by 10 U.S. exclusively owned issued and pending patents and over 60 exclusively owned foreign issued
and pending patents.
About Neuralstem
Neuralstem is a clinical-stage biopharmaceutical company developing novel treatments for nervous system diseases of
high unmet medical need. NSI-189 is a small molecule in clinical development for major depressive disorder (MDD) and in
preclinical development for Angelman syndrome, irradiation-induced cognitive impairment, Type 1 and Type 2 diabetes, and
stroke. NSI-566 is a stem cell therapy being tested for treatment of paralysis in stroke, chronic spinal cord injury (cSCI)
and Amyotrophic Lateral Sclerosis (ALS). Neuralstem’s diversified portfolio of product candidates is based on its proprietary
neural stem cell technology.
Cautionary Statement Regarding Forward Looking Information
This news release contains “forward-looking statements” made pursuant to the “safe harbor” provisions of the Private Securities
Litigation Reform Act of 1995. Such forward-looking statements relate to future, not past, events and may often be identified by
words such as “expect,” “anticipate,” “intend,” “plan,” “believe,” “seek” or “will.” Forward-looking statements by their nature
address matters that are, to different degrees, uncertain. Specific risks and uncertainties that could cause our actual results to
differ materially from those expressed in our forward-looking statements include risks inherent in the development and
commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for
future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ
materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could
affect our results and other risks and uncertainties are detailed from time to time in Neuralstem’s periodic reports, including the
Annual Report on Form 10-K for the year ended December 31, 2016, and Form 10-Q for the three and nine months ended September 30,
2017, filed with the Securities and Exchange Commission (SEC), and in other reports filed with the SEC. We do not assume any
obligation to update any forward-looking statements.
Contact:
Kimberly Minarovich
Argot Partners (Investor Relations)
212-600-1902
kimberly@argotpartners.com
