Two near-term data catalysts expected in
2023
- Entered active collaboration with Alvogen
Pharmaceuticals and Lotus Pharmaceuticals for global development
and commercialization of NRX-101 in suicidal bipolar depression;
potential for up to $330 million in
milestones and double-digit royalties
- Publication of STABIL-B trial in the International
Journal of Bipolar Disorders: first oral antidepressant to
demonstrate reduction in suicidality with significant improvement
in depression scores compared to standard of care
medication
- Ongoing Phase 2b/3 trial of
NRX-101 in suicidal bipolar depression is within 20 patients of
data readout. Data expected in Q4 2023
- Newly released data demonstrate high levels of compliance
and inter-rater reliability
- Licensed US Patent for use of D-Cycloserine (DCS) to
treat chronic pain
- Announced plan to develop NRX-101™ for chronic
pain indications, awaiting results of 200 person DOD-funded trial
in treatment of chronic pain with DCS in coming months
- Filing Investigational New Drug application with FDA to
treat chronic pain with NRX-101
- Management to host a conference call today at 4:30 PM ET
RADNOR,
Pa., Aug. 14, 2023 /PRNewswire/ -- NRx
Pharmaceuticals, Inc. (Nasdaq: NRXP) ("NRx Pharmaceuticals", the
"Company"), a clinical-stage biopharmaceutical company, today
announced its financial results for the second quarter ended
June 30, 2023, and provided a
business update.
"We anticipate multiple near-term data catalysts in our suicidal
bipolar depression and chronic pain clinical programs. Our internal
focus has been on driving our ongoing phase 2b/3 trial to a data readout, which we expect in
Q4 2023. The newly-published peer-reviewed results from our phase 2
STABIL-B trial document that NRX-101 is the first oral
antidepressant to demonstrate a statistically significant reduction
in suicidality together with a statistically-significant reduction
in depression compared to standard of care medication. Today, we
have posted blinded results from our ongoing clinical trial
documenting the 94% concordance in measurement of the primary
endpoint (i.e. the MADRS depression scale) between our study sites
and our internal master raters. Psychiatry trials often succeed or
fail based on their ability to control the accuracy with which the
endpoints are measured and this measure of Inter-rater reliability
exceeds that reported in the published literature." said
Stephen Willard, J.D., Chief
Executive Officer and Director of NRx Pharmaceuticals. "We have now
operationalized our collaboration with Alvogen Pharmaceuticals with
teams of Alvogen and Lotus scientists working side by side with us
to map and execute the late-stage development and global
commercialization of NRX-101 for bipolar depression. This
represents a substantial investment in corporate resources on the
part of our partner, which, in our view, both de-risks the NRX-101
drug development program and reduces the future dilution to our
shareholders that would otherwise be associated with executing a
phase 3 trial and commercial launch.
"The Alvogen collaboration and the prospect of support for phase
3 and commercial development of our bipolar depression program has
afforded us the flexibility to expand our target indications of
NRX-101 to the much larger indication of chronic pain.
Whereas 7 million Americans are estimated to suffer from bipolar
depression, more than 50 million Americans suffer from chronic
pain. (Rikard SM, Strahan AE, Schmit KM, Guy Jr GP. Chronic pain
among adults—United States, 2019–2021. Morbidity and Mortality
Weekly Report. 2023;72(15):379.) We began our work in bipolar
depression, a vital unmet medical need, at a time when opioids were
a predominant treatment for chronic pain and market wisdom
suggested that nonaddictive innovative drugs could not compete
effectively with generic opioids. An overwhelming shift in
public health policy and public awareness, creates an urgent need
for non-addictive, non-neurotoxic treatments for chronic pain. We
have shared with the public a comprehensive review paper detailing
twenty years of nonclinical and early clinical research that
suggests the potential for NRX-101 to treat chronic pain in a
non-addictive manner that may actually decrease patient desire for
opioids. That is the impetus for licensure of US Patent 8,653,120,
which dovetails with our existing composition of matter protection
for NRX-101. We await the near-term readout of the approximately
200 person clinical trial of DCS in Chronic Pain funded by the US
Department of Defense (clinicaltrials.gov NCT03535688) that has now
been concluded and awaits statistical readout. As previously
announced, we have completed our phase 3 and commercial
manufacturing program for NRX-101 and this week we are opening an
Investigational New Drug file with the FDA for use of NRX-101 to
treat chronic pain."
Second Quarter Clinical and Regulatory Highlights
NRX-101 Indication – Bipolar Depression with Suicidality
- NRX-101, a fixed dose combination of D-cycloserine and
lurasidone, has been granted Fast Track Designation, Breakthrough
Therapy Designation, a Special Protocol Agreement, and a Biomarker
Letter of Support from the FDA for Severe Bipolar Depression with
Acute Suicidal Ideation. At the suggestion of FDA, the Company
seeks to broaden that indication to Bipolar Depression with
suicidality.
- The Company's STABIL-B trial was accepted for publication
in the International Journal of Bipolar Disorders, a peer-reviewed
publication (Nierenberg A, Lavin P, Javitt DC, et al. NRX-101
(D-cycloserine plus lurasidone) vs. lurasidone for the maintenance
of initial stabilization after ketamine in patients with severe
bipolar depression with acute suicidal ideation and behavior: a
randomized prospective phase 2 trial. Int J Bipolar Disord.
2023;11(1):28. PMID:37573534 doi:10.1186/s40345-023-00308-5). The
results document superiority of NRX-101 over lurasidone in
controlling depression and suicidality in acutely suicidal patients
following stabilization with ketamine.
- The Company similarly achieved peer-reviewed publication of its
study demonstrating the lack of acute neurotoxicity with
NRX-101
(https://journalbipolardisorders.springeropen.com/articles/10.1186/s40345-023-00308-5#citeas)
and the lack of addictive potential for NRX-101 (Sapko MT, Hanania
T, Chang Q, Javitt JC. D-cycloserine is not susceptible to
self-administration using an intravenous self-administration model
in male ketamine-habituated Sprague-Dawley rats. Pharmacol
Biochem Behav. 2023;227-228:173586. PMID:37330114
doi:10.1016/j.pbb.2023.173586).
- In June, the Company announced an agreement with Alvogen
Pharmaceuticals and Lotus Pharmaceuticals to fund the late-stage
clinical trials of NRX-101 and to bring it to a global patient
population with suicidality.
- Upon payment of the first $10
million milestone, triggered by positive clinical data from
the ongoing trial and FDA comments, Alvogen will be
responsible for all development, regulatory and commercial costs of
NRX-101 in this indication.
- Under guidance from the FDA and based on the Company's
completion of manufacturing for Phase 3 and commercial stage
product, the ongoing clinical trial of NRX-101 compared
with lurasidone in patients bipolar depression and suicidality
(C-SSRS 3 and 4) has been upgraded to a Phase 2b/3 trial that will seek use as a registrational
trial.
- Enrollment is ongoing in the multi-center, randomized,
double-blind controlled Phase 2b/3
clinical trial of NRX-101 compared to lurasidone in Bipolar
Depression with Suicidality. The study's objective is to
demonstrate a decrease in depression scores (MADRS) and scores for
suicidal ideation (CGI-SS) in patients treated with NRX-101
compared to those treated with lurasidone
alone.(www.clinicaltrial.gov NCT03395392 ) The Phase 2 portion of
the trial is designed to observe the effect in 70 patients with the
option to expand enrollment if deemed appropriate by the Data
Safety Monitoring Board at an interim readout.
- Today we have released data that provide insight into trial
integrity :
-
- Compliance with assigned medication is tracking above 90%, as
reported by our Contract Research Organization, which exceeds
expectation for a CNS study
- As we report this week in the scientific literature
(https://www.authorea.com/users/321659/articles/659448-real-time-quality-assurance-of-depression-ratings-in-psychiatric-clinical-trials),
congruence of site administered depression ratings (MADRS)
evaluations with our internal "master raters" are tracking above
94% for our 3 point congruence standard and above 97% for the less
restrictive 6 point standard reported in the literature. This level
of rating congruence exceeds that reported in the peer-reviewed
literature and provides a basis for believing that the is
collecting data that will be interpretable after unblinding.
- In March 2023, a Data Safety
Monitoring Board (DSMB) meeting noted that the trial demonstrated
non-futility and no unexpected safety concerns.
- Study enrollment has expanded with a data readout expected near
year end 2023.
NRX-101 Indication – Chronic Pain
- In June 2023, concurrent with
announcement of the Alvogen partnership, the Company announced
an expansion of its NRX-101 program to encompass treatment of
chronic pain as the next focus on NRX-101's development.
- Last week, the company announced the licensure of US Patent
8,653,120 related to the treatment of chronic pain with DCS
and the addition of Dr. Vania
Apkarian, Professor of Physiology, Anesthesia, Surgery, and
Neuroscience Institute, Northwestern
University Feinberg School of Medicine, to the NRx
Scientific Advisory Board. Dr. Apkarian is the inventor of
the patent and a global expert in pain research and has important
experience studying DCS in chronic pain.
- Chronic pain is estimated to be a $72
billion industry today with the potential to grow to a
$120 billion industry by 2033.
- DCS has been shown to modulate the Pain Pathway at each point
in the neural chain of pain: transmission at dorsal horn of
the spinal cord, pain perception in the thalamus ("paleo brain"),
and pain memory and processing between the paleo brain and the
cortex.
- In experimental models and clinical studies, NMDA
antagonists have demonstrated attenuation of pain and shown
potential in reducing opioid craving.
- Additionally, DCS has demonstrated no potential for
addiction, unlike ketamine and other NMDA antagonists that bind to
the "mu" opioid receptor.
- D-cycloserine was evaluated in a pilot study at Northwestern University and showed efficacy at the
higher dose levels in the study (Schnitzer, 2016). DCS is
currently being examined in a confirmatory trial funded by the US
Department of Defense under the Congressionally Directed Medical
Research Program. The trial seeks to recruit approximately 200
participants with chronic low back pain at Northwestern University (clinicaltrials.gov
NCT03535688).[1] Data collection is complete
and statistical results are expected in the coming months.
- Research conducted by NRx Pharmaceuticals demonstrated a
25 μg/ml dose at which D-cycloserine becomes an NMDA antagonist.
The 400mg dose presented in the confirmatory trial at Northwestern University is at the lower end of the
threshold and suggests that the ability to increase the
D-cycloserine dose beyond 400mg, where lurasidone is used to
prevent CNS side effects in NRX-101.
NRX-101 Indication – Post Traumatic Stress Disorder (PTSD)
- NRx plans to investigate NRX-101 in PTSD as an additional
indication. The Company expects to commence planning for a Phase 2
clinical trial in 2023.
- Depression in PTSD may be driven by pathways that are
similar to those that drive depression in other conditions (NMDA
and 5-HT2A). Additionally, approximately 10% of patients with PTSD
may experience suicidality, especially those with severe PTSD.
- In a preclinical PTSD study, D-cycloserine, a component of
NRX-101, demonstrated the ability to extinguish recurring images of
traumatic events, also known as fear memory, in a validated WKY
model of PTSD. Ketamine has demonstrated an effect on this
debilitating symptom of PTSD. Should NRX-101 have a similar
beneficial effect, it has the potential to be the first labeled
medicine for PTSD symptoms.
Second Quarter Corporate Updates
- On June 5, 2023, the Company
announced it had entered a strategic partnership with Lotus
Pharmaceuticals and Alvogen Pharmaceuticals to further work
towards the development and commercialization of NRX-101 for
suicidal treatment-resistant bipolar depression for global markets.
Under the terms of the agreement, NRx is entitled to receive
$10 million upon a successful Phase
2b/3 data readout and completion of
an FDA Type B meeting. NRx is eligible to receive payment of
$5 million upon receipt of FDA
approval for NRX-101 as well as bonus milestone payments of up to
$315 million based on reaching
certain net sales targets. Further, NRx will receive royalty
payments on net sales, which escalate to the mid-teens.
Additionally, Lotus Pharmaceuticals will be responsible for
commercialization of NRX-101 in markets outside of the U.S., while
Alvogen will work with their CNS branded subsidiary, Almatica, to
commercialize NRX-101 in the U.S. market.
- In June 2023, the Company closed
a $6.28 million registered direct
offering with H.C. Wainwright. NRx intends to use the net
proceeds from the offering for working capital and general
corporate purposes and may use the net proceeds to initiate
research into the use of NRX-101 for the treatment of chronic pain
and PTSD.
- In June 2023, the Company
negotiated a payment arrangement with Streeterville Capital to
reduce cash monthly redemptions of its loan to no more than
$400,000 per month through year end
2023.
Financial Results for the Second Quarter Ended June 30, 2023
- For the three months ended June
30, 2023, NRx Pharmaceuticals recorded $3.9 million of research and development expenses
compared to $3.0 million for the
three months ended June 30, 2022. The
increase of $0.9 million is related
primarily to an increase of $1.3
million in clinical trials and development expenses related
to the NRX-101 program for Suicidal Treatment-Resistant Bipolar
Depression partially offset by a decrease in various other
costs.
- For the six months ended June 30,
2023, NRx Pharmaceuticals recorded $7.5
million of research and development expenses compared to
$8.4 million for the six months ended
June 30, 2022. The decrease of
$0.9 million is related primarily to
a decrease of $0.6 million in
clinical trials and development expenses related to ZYESAMI,
$0.5 million related to fees paid to
regulatory and process development consultants, $0.2 million in stock-based compensation,
partially offset by an increase in various other costs.
- For the three months ended June
30, 2023, NRx Pharmaceuticals recorded $4.1 million of general and administrative
expenses compared to $6.6 million for
the six months ended June 30, 2022.
The decrease of $2.5 million is
related primarily to a decrease of $1.0
million in insurance expenses, $0.7
million in consultant fees, $0.7
million in legal, professional and accounting fees,
partially offset by an increase in various other costs.
- For the six months ended June 30,
2023, NRx Pharmaceuticals recorded $9.9
million of general and administrative expenses compared to
$16.9 million for the six months
ended June 30, 2022. The decrease of
$7.0 million is related primarily to
a decrease of $4.6 million
in legal, professional and accounting fees, $1.6 million in insurance expenses, $0.9 million in stock-based compensation expense,
partially offset by an increase in various other costs.
- For the three months and ended June
30, 2023, NRx Pharmaceuticals recorded $8.7 million in net loss compared to $7.0 million for the quarter ended June 30, 2022. For the six months and ended
June 30, 2023, NRx Pharmaceuticals
recorded $19.8 million in net loss
compared to $20.4 million for the
quarter ended June 30, 2022.
- As of June 30, 2023, we had
$15.0 million in cash and cash
equivalents. These working capital assets are expected to fund the
Company's operations through the fourth quarter of this year, which
is when we expect data from our ongoing Phase 2b/3 trial. Additionally, we are evaluating
operational efficiencies to extend this runway.
Conference Call and Webcast Details
A live webcast of the conference call will be available on the
Company's website today at 4:30 p.m.
ET,
at https://ir.nrxpharma.com/news-events/ir-calendar. An
archive of the webcast will be available on the Company's website
for 30 days. Participants that are unable to join the webcast
can access the conference call via telephone by dialing
domestically +1 (833) 630-1956 or internationally +1 (412)
317-1837.
About NRX-101
NRX-101, a fixed dose combination of D-cycloserine and
lurasidone, has been granted Fast Track Designation, Breakthrough
Therapy Designation, a Special Protocol Agreement, and a Biomarker
Letter of Support from the FDA for Bipolar Depression with
Suicidality. NRX-101 is further being developed for chronic
pain and PTSD.
Up to 50% of individuals with bipolar disorder attempt suicide
over their lifetime, and estimates indicate that up to 20% may die
by suicide. The only FDA-approved treatment for patients with
suicidal bipolar depression remains electroconvulsive therapy.
Conventional antidepressants can increase the risk of suicide in
certain patients; hence their labels contain a warning to that
effect. NRX-101 is a patented, oral, fixed dose combination of
D-cycloserine and lurasidone, neither of which has shown addiction
potential in preclinical models. Based on the results of the
STABIL-B trial, NRX-101 received Breakthrough Therapy Designation
from the FDA for the treatment of patients with severe bipolar
depression and acute suicidality after initial stabilization with
ketamine or other effective therapy.
NRX-101 is one of the first oral antidepressants currently in
late-stage clinical studies targeting the NMDA-receptor in the
brain, which represents potentially a key new mechanism to treat
depression with and without suicidality, as well as chronic pain,
PTSD and other indications.
About NRx Pharmaceuticals
NRx Pharmaceuticals is a clinical-stage biopharmaceutical
company developing therapeutics based on its NMDA platform for the
treatment of central nervous system disorders, specifically
suicidal bipolar depression, chronic pain and PTSD. The Company's
lead program NRX-101, an oral, fixed-dose combination of
D-cycloserine and lurasidone, targets the brain's
N-methyl-D-aspartate (NMDA) receptor and is being developed for
patients who suffer from suicidal bipolar depression and those who
suffer from chronic pain. The Company has partnered with Alvogen
Pharmaceuticals, who owns the worldwide rights to NRX-101 for
treatment of bipolar depression with suicidality, to help bring
NRX-101 to a global population of patients with unmet medical need.
NRx Pharmaceuticals is currently exploring NRX-101's potential to
act as a non-opioid chronic pain treatment option and is continuing
to plan an exploratory trial in the treatment of PTSD.
Cautionary Note Regarding Forward-Looking Statements
This announcement of NRx Pharmaceuticals, Inc. includes
"forward-looking statements" within the meaning of the "safe
harbor" provisions of the U.S. Private Securities Litigation Reform
Act of 1995, which may include, but are not limited to, statements
regarding our financial outlook, product development, business
prospects, and market and industry trends and conditions, as well
as the Company's strategies, plans, objectives, and goals. These
forward-looking statements are based on current beliefs,
expectations, estimates, forecasts, and projections of, as well as
assumptions made by, and information currently available to, the
Company's management.
The Company assumes no obligation to revise any forward-looking
statement, whether as a result of new information, future events or
otherwise. Accordingly, you should not place reliance on any
forward-looking statement, and all forward-looking statements are
herein qualified by reference to the cautionary statements set
forth above.
NRX PHARMACEUTICALS,
INC.
CONDENSED CONSOLIDATED
BALANCE SHEETS
(in thousands,
except share and per share data)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
June 30,
2023
|
|
December 31,
2022
|
|
|
(Unaudited)
|
|
|
|
ASSETS
|
|
|
|
|
|
|
Current
assets:
|
|
|
|
|
|
|
Cash and cash
equivalents
|
|
$
|
14,969
|
|
$
|
20,054
|
Prepaid expenses and
other current assets
|
|
|
4,819
|
|
|
5,741
|
Total current
assets
|
|
|
19,788
|
|
|
25,795
|
Other assets
|
|
|
21
|
|
|
21
|
Total
assets
|
|
$
|
19,809
|
|
$
|
25,816
|
LIABILITIES AND
STOCKHOLDERS' (DEFICIT)
EQUITY
|
|
|
|
|
|
|
Current
liabilities:
|
|
|
|
|
|
|
Accounts
payable
|
|
$
|
2,205
|
|
$
|
2,076
|
Accrued and other
current liabilities
|
|
|
5,783
|
|
|
4,855
|
Accrued clinical site
costs
|
|
|
1,115
|
|
|
914
|
Convertible note
payable and accrued interest -
short term
|
|
|
12,692
|
|
|
7,703
|
Insurance loan
payable
|
|
|
786
|
|
|
—
|
Warrant
liabilities
|
|
|
36
|
|
|
37
|
Total current
liabilities
|
|
|
22,617
|
|
|
15,585
|
Convertible note
payable and accrued interest -
long term
|
|
|
—
|
|
|
2,822
|
Total
liabilities
|
|
$
|
22,617
|
|
$
|
18,407
|
|
|
|
|
|
|
|
Preferred stock, $0.001
par value,
50,000,000 shares authorized; 0 shares issued
and
outstanding at June 30, 2023
and
December 31, 2022, respectively
|
|
|
—
|
|
|
—
|
Common stock, $0.001
par value,
500,000,000 shares authorized;
80,388,330 and 66,442,989 shares
issued and outstanding at June 30, 2023
and
December 31, 2022, respectively
|
|
|
80
|
|
|
67
|
Additional paid-in
capital
|
|
|
239,887
|
|
|
230,339
|
Accumulated other
comprehensive (loss) income
|
|
|
(22)
|
|
|
—
|
Accumulated
deficit
|
|
|
(242,753)
|
|
|
(222,997)
|
Total stockholders'
(deficit) equity
|
|
|
(2,808)
|
|
|
7,409
|
Total liabilities and
stockholders' (deficit) equity
|
|
$
|
19,809
|
|
$
|
25,816
|
The accompanying notes are an integral part of
these unaudited condensed consolidated financial statements.
NRX PHARMACEUTICALS,
INC.
CONDENSED
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE
LOSS
(in thousands,
except share and per share data)
(Unaudited)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Three months
ended
|
|
Six months
ended
|
|
|
June 30,
|
|
June 30,
|
|
|
2023
|
|
2022
|
|
2023
|
|
2022
|
Operating
expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
Research and
development
|
|
$
|
3,873
|
|
$
|
2,958
|
|
$
|
7,523
|
|
$
|
8,441
|
General and
administrative
|
|
|
4,065
|
|
|
6,642
|
|
|
9,850
|
|
|
16,864
|
Settlement
expense
|
|
|
250
|
|
|
—
|
|
|
250
|
|
|
—
|
Total operating
expenses
|
|
|
8,188
|
|
|
9,600
|
|
|
17,623
|
|
|
25,305
|
Loss from
operations
|
|
|
(8,188)
|
|
|
(9,600)
|
|
|
(17,623)
|
|
|
(25,305)
|
Other (income)
expenses:
|
|
|
|
|
|
|
|
|
|
|
|
|
Interest
income
|
|
|
(145)
|
|
|
(23)
|
|
|
(301)
|
|
|
(23)
|
Interest
expense
|
|
|
—
|
|
|
—
|
|
|
—
|
|
|
3
|
Change in fair value
of convertible note payable
|
|
|
663
|
|
|
—
|
|
|
2,435
|
|
|
—
|
Change in fair value
of warrant liabilities
|
|
|
11
|
|
|
(116)
|
|
|
(1)
|
|
|
(273)
|
Change in fair value
of Earnout Cash liability
|
|
|
—
|
|
|
(2,479)
|
|
|
—
|
|
|
(4,582)
|
Total other (income)
expenses
|
|
|
529
|
|
|
(2,618)
|
|
|
2,133
|
|
|
(4,875)
|
Net loss
|
|
$
|
(8,717)
|
|
$
|
(6,982)
|
|
$
|
(19,756)
|
|
$
|
(20,430)
|
Change in fair value of
convertible note attributed
to credit risk
|
|
|
128
|
|
|
—
|
|
|
22
|
|
|
—
|
Other comprehensive
loss
|
|
|
128
|
|
|
—
|
|
|
22
|
|
|
—
|
Comprehensive
loss
|
|
$
|
(8,845)
|
|
$
|
(6,982)
|
|
$
|
(19,778)
|
|
$
|
(20,430)
|
Net loss per
share:
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and
diluted
|
|
$
|
(0.12)
|
|
$
|
(0.11)
|
|
$
|
(0.28)
|
|
$
|
(0.32)
|
Weighted average
common shares
outstanding:
|
|
|
|
|
|
|
|
|
|
|
|
|
Basic and
diluted
|
|
|
73,221,563
|
|
|
65,732,343
|
|
|
70,260,622
|
|
|
64,348,966
|
1
https://classic.clinicaltrials.gov/ct2/show/NCT03535688
View original
content:https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-reports-second-quarter-2023-financial-results-and-provides-business-update-301900151.html
SOURCE NRx Pharmaceuticals, Inc.