Full Press Release Details
NRx is a clinical-stage pharmaceutical company
which develops, through its wholly-owned operating subsidiaries, NeuroRx, Inc., a Delaware corporation and NeuroRx 2015 LTD, an Israeli
corporation, novel therapeutics for the treatment of central nervous system disorders and life-threatening pulmonary diseases. We are
developing four pharmaceutical products as shown below: NRX-100 and NRX-101, awarded the Breakthrough Therapy designation by the FDA for
treatment of suicidal bipolar depression and PTSD; ZYESAMITM (aviptadil acetate), an FDA Fast Track-designated, investigational, pre-commercial
drug for COVID-19 related respiratory failure; and BriLife , a live-virus vaccine targeting SARS-CoV-2 wild type and variant infections
to prevent COVID-19.
NRx Products in Development
NRX-101 has demonstrated a statistically-significant
reduction in depression and suicidality in a randomized trial against an active comparator (lurasidone) and has been awarded FDA Breakthrough
Therapy Designation, a Special Protocol Agreement and a Biomarker Letter of Support.
ZYESAMI, as a sterile liquid for intravenous
use has demonstrated a statistically-significant reduction in mortality compared to placebo in patients with critical COVID-19 and respiratory
failure using the statistical methodology agreed in advance with FDA, which controls for differences in baseline severity of disease (if
one does not control for baseline severity, a numerical but not statistically-significant advantage is seen). ZYESAMI has been
approved for Emergency Use by the Nation of Georgia with pending applications in surrounding Caucasus nations and has been submitted for
EUA to the FDA where it is currently awaiting a regulatory decision. Applications to other regulatory authorities worldwide are in process.
Additional Phase III trials of ZYESAMI are now being conducted by the US National Institutes of Health (NIH) and by an entity funded
The BriLife vaccine has demonstrated a statistically-significant
increase in COVID-neutralizing antibody - a sign of immunity to SARS-CoV-2 - compared to placebo in Phase 2a trials conducted in Israel
and is currently completing Phase 2b dose-ranging trials in Israel and Georgia.
History of our development of NRX-100/101 for suicidal depression
and post-traumatic stress disorder
NRx was founded in 2015 by Drs. Jonathan and Daniel
Javitt in order to develop drugs to treat psychiatric disorders based on Daniel Javitt's discovery of a synergistic effect when
NMDA antagonists are combined with inhibitors of the brain's 5-HT2A receptor (e.g., SSRI antidepressants and atypical antipsychotic
drugs). This synergy has now been demonstrated in both laboratory rodent behavioral experiments and in multiple Phase 2 clinical trials.
Dr. Daniel Javitt observed that when patients with depression were treated with DCS, an NMDA antagonist, they manifested increased antidepressant
effect, but did not exhibit the hallucinations and other NMDA effects previously reported with DCS. He further observed that the DCS appeared
to blunt the antidepressant side effects (akathisia) common to all known serotonin-targeted anti-depressants.
These discoveries support NRX-101, the first
investigational oral antidepressant to be granted Breakthrough Therapy designation and a Special Protocol Agreement by the FDA for Severe
Bipolar Depression in Patients with Acute Suicidal Ideation & Behavior. We are concentrated on the research, development and commercialization
of this and other products for the treatment of patients suffering from suicidal ideation in the setting of bipolar depression and major
depressive disorder ("MDD") as well as PTSD and obsessive compulsive disorder. Drugs that inhibit the brain's
NMDA receptor have been explored for the treatment of the above conditions since the finding that ketamine has potent effects in reducing
depressive and suicidal ideation. However, attempts by other drug manufacturers to use NMDA-inhibiting drugs for this purpose have been
limited by neurotoxicity, hallucinations, habituation (i.e., addictive properties), blood pressure elevations, and lack of oral
This synergy is the key discovery underlying
the patent portfolio described below. The side effects of NMDA drug are blocked by the 5-HT2A drug and, in turn, the NMDA component blocks
akathisia, a known side effect of 5-HT2A-blocking drugs which is known to predispose to suicide. This dual-targeted approach, to our knowledge
is the basis of our worldwide patent portfolio, which currently encompasses 40+ filed patent applications, and 30+ issued patents in multiple
jurisdictions covering both Compositions of Matter and Methods of Use. The relevant patents and patent applications in this portfolio
are either owned by NRx, exclusively licensed to NRx by Glytech, a Delaware limited liability corporation solely owned by Dr. Daniel Javitt
(the "Glytech License"), or licensed to NRx by Sarah Herzog Memorial Hospital Ezrat Nashim ("SHMH"),
a non-profit organization organized under the laws of the State of Israel (the "SHMH License").
Patents under the Glytech License, which cover
compositions of matter (including NRX-101 and pipeline therapeutic candidates) and methods of use (including methods of using NRX-101
in treatment of bipolar depression with suicidal ideation and in treating PTSD) have been granted in the U.S., Europe (including validation
in 18 members of the European Patent Convention), Japan, Australia and China. Additional patent applications under the Glytech License
(covering compositions of matter and methods of use of pipeline therapeutic candidates, and methods of use of NRX-101 in treating additional
depressive disorders) are pending in each of these countries as well as in Canada. Assuming all maintenance fees are timely paid in each
jurisdiction and that the patents are not held invalid or unenforceable by a court or patent office, the patents licensed to NRx by Glytech
will expire in each jurisdiction in which they have been granted in 2033 (for the base NRX-101 patents) and 2038 (for the PTSD treatment
patents). See "Summary of NRx Material In-licensing Obligations - NRX-100/101 - Glytech Development and License Agreement"
for more information.
Patents under the SHMH License, which cover
compositions of matter that may represent pipeline therapeutic candidates for NRx, and methods of use of such compositions in treating
certain depressive disorders, have been granted in the U.S. and Europe with additional patent applications covering similar subject matter
pending in these countries and in Israel and Canada. Assuming all maintenance fees are timely paid in each jurisdiction and that the patents
are not held invalid or unenforceable by a court or patent office, the patents licensed to NRx by SHMH will expire in each jurisdiction
in which they have been granted in 2032. See "Summary of NRx Material In-licensing Obligations - NRX-100/101 - Sarah Herzog Memorial
Hospital License Agreement" for more information.
History of ZYESAMI Development
We completed a Phase 3 clinical trial and submitted
an EUA with the FDA on May 31, 2021 of ZYESAMI to treat COVID-19, a life-threatening respiratory condition, and are in Phase 3 clinical
development of drug products to treat life-threatening central nervous system conditions. The respiratory product class of products to
market is based upon the neuropeptide VIP that is secreted by neuroendocrine cells throughout the body, and is concentrated in the human
lung and brain. VIP showed promise for treating Acute Respiratory Distress Syndrome ("ARDS") in 2005 and became
uniquely important in 2020 when it was demonstrated to have potential to treat COVID-19.
Aviptadil is the generic name for synthetically-manufactured
VIP, as distinct from the natural peptide. Our first VIP-derived product - ZYESAMI (a reformulation of RLF-100), our COVID-19 drug - was
designation by the FDA in June 2020 and admitted to the Coronavirus Treatment Acceleration Program. The term "VIP"
should be interpreted as referring to the natural peptide produced in the human body, while the terms "aviptadil" and "ZYESAMI"
refer to our drug substance (i.e., active pharmaceutical ingredient) and drug product, respectively. We have completed a Phase
IIb/III randomized controlled trial of ZYESAMI vs. placebo (NCT 04311697), conducted under FDA Fast Track designation. The Phase IIb/III
trial enrolled 196 patients and the last patient completed 60 days of observation on February 24, 2021. Across all patients and sites,
ZYESAMI met the primary prespecified endpoint for "alive and free of respiratory failure" at day 60 (P = .02) when adjusting
for ventilation status and treatment site, and demonstrated a statistically significant increase in odds of survival through day 60, whether
or not the participant was fully recovered (P = <.01). The statistical analysis plan submitted to the FDA prior to commencement of
the study specified that statistical regression analysis would be used to make such adjustments. With adjustment for baseline severity
as agreed upon with the FDA prior to the study but without adjustment for treatment site, there is a statistically significant two-fold
increased odds of survival seen in patients treated with ZYESAMI at 60 days compared to those treated with placebo (P<.05).
Morbidity and mortality in COVID-19 is widely
believed to be associated with release of inflammatory cytokines, particularly interleukine 6 (IL-6). Across all patients and sites of
care in our study, those treated with placebo showed a ten-fold increase in blood IL-6 levels within 7 days of treatment, while those
treated with ZYESAMI showed a 2-fold increase (P<.02). Preventing this rise in IL-6 was statistically correlated with improved survival
in ZYESAMI-treated patients (P<.0001).
To our knowledge, ZYESAMI is the first COVID-19
therapeutic to achieve these results in a randomized, double-blind multicenter trial. Although these results do not provide a guarantee
that ZYESAMI will be deemed to be safe or effective for the treatment of COVID-19 and extensive clinical testing and regulatory approval
will be required before ZYESAMI can commonly be prescribed for the treatment of COVID-19, on the basis of these findings, we applied for
EUA with the FDA on May 31, 2021, and plan to apply for Breakthrough Therapy Designation and to submit an application for an NDA. Additional
trials are being conducted via the NIH-sponsored ACTIV3 program and the I-SPY program.
ZYESAMI is named for Professor Sami Said, Distinguished
Professor at the State University of New York at Stony Brook, who discovered VIP in 1970 and published more than 370 peer-reviewed studies
on its effects. Its potential effectiveness in COVID-19 is based on the principle that the coronavirus specifically invades the Alveolar
Type II cell of the pulmonary (lung) epithelium, where it blocks surfactant production, replicates into millions of virus particles, unleashes
inflammatory cytokines, causes cell death type, and shuts down production of surfactant, which is the fluid that lines the lung and allows
oxygen to pass from the air to the blood. ZYESAMI is shown in preclinical laboratory experiments at the Oswaldo Cruz Institute (Rio de