Broad-Spectrum Direct Antiviral Nanomedicine
Should
Remain Effective Against COVID-19 Virus
Variants,
Says NanoViricides,
Inc.'s
President, Dr. Anil Diwan
Shelton, CT - January 26, 2021 -- NanoViricides,
Inc. (NYSE American: NNVC)
(the "Company") a global leader in the development of highly
effective broad-spectrum antiviral therapies based on a novel
nanomedicines platform, today
discusses the current developments in the COVID-19 pandemic and the
Company's exciting
accomplishments related to it.
"We
welcome the strong engagement of President Biden and his new
administration's commitment to
combat this once-in-a-century pandemic with
new approaches and fresh ideas," said Anil R. Diwan,
PhD, President of the Company.
We would
like to note that the scientific community at large and regulatory
efforts to date have remained focused on (a) vaccines, (b)
antibodies, and (c) re-development of pre-existing drugs. Even as
alarm bells were raised by renowned scientists regarding the
likelihood of escape mutations and the limitations of any vaccines
and antibody therapies in combating a rapidly evolving global viral
pandemic, there has been an effort to downplay these risks at all
levels. This has left the world now grappling
with
a situation where vaccines are being rolled out even as virus
variants that are highly likely to be resistant to current vaccines
and antibody drugs have already been found to be spreading rapidly.
Current vaccines are now assumed to require constant
updates and
re-inoculation campaigns to keep up with ongoing changes in the
virus. Attention needs to be focused instead on broad-spectrum
antiviral therapeutics that minimize the possibility of virus
variants escaping the drug, thereby making the costly
ongoing development of
vaccine updates, their deployment and re-inoculation campaigns
unnecessary.
NanoViricides
believes it is
very
likely the only company with a platform technology that enables
development of drugs that viruses would not escape.
In fact,
we
have successfully screened our COVID-19 drug candidates to be able
to protect cells against infection by distinctly different
coronaviruses. This broad-spectrum drug development approach was
adopted to ensure that our drug candidates should remain
effective even as future
variants of SARS-CoV-2 evolve in the field, as was already
anticipated by us at that time.
Additionally,
NanoViricides is the only company
that, to the best of our knowledge, is developing antiviral
treatments designed
to (a)
directly attack the virus
and disable it from infecting human cells, and (b) simultaneously
block the reproduction of the virus that has already gone inside a
cell. Together, this strategy of a two-pronged attack against the
virus, both inside the cell and outside the cell, can be
expected to result in a cure for coronaviruses and other viruses
that do not become latent.
The
Company's
nanoviricides® platform technology
is based on biomimetic engineering that copies the features of the
human cellular receptor of the virus. No matter how much the virus
mutates, all virus variants bind to the same receptor in the same
fashion. It appears
that the later
variants of SARS-CoV-2 may
have evolved to bind to the
human
cellular receptor ACE2 more
strongly,
in general, based on published
datasets. Thus, if these
features of the cellular receptor are appropriately copied, the
resulting nanoviricide drug
would remain effective against current and future variants
of the
virus.
Our
current drug candidates to combat the COVID-19 pandemic are
designed to attack not only SARS-CoV-2 and its current and future
variants, but also many other coronaviruses, and
will be
useful even after the pandemic is over, because several
coronaviruses are endemic in human populations.
Our
COVID-19 drug candidates
successfully entered core safety pharmacology studies required
prior to any human clinical trials
around October/November, 2019. These studies have now been
completed and we are anticipating the report from the external CRO
shortly. We are now working on preparing a pre-IND
application for filing with the
US FDA as soon as possible. Additionally, we are
actively seeking opportunities to engage appropriate sites for
human clinical trials, and we are engaged in the preparation of
clinical trial protocols and other activities that would be
necessary for filing of an IND with the US FDA.
The need
for the broad-spectrum nanoviricide SARS-CoV-2 drug cannot be
overstated in the current circumstances and the present
status of
the pandemic. To understanding this, we are providing a short
review of the current state of the pandemic below:
Strong
government support
led to rapid emergency use approval, and later full approval,
of an already known
antiviral drug now called Veklury (remdesivir, Gilead) early on.
Strong fiscal support and regulatory enablements from the
government also led to the emergency use approval of
two different antibody drugs, one from Regeneron (REGN-CoV-2, a
monoclonal antibody cocktail containing two different antibodies),
and one from Eli Lilly (bamlanivimab, a single antibody for
restricted use) in the fastest ever drug development timeframe.
All of these antibody drugs target the viral Spike protein that
binds to the human cellular receptor, ACE2.
Even
stronger commitments and strong government support led to the
fastest ever emergency use approval of two vaccines, both employing
nanotechnology; one by
Pfizer-BioNTech, and one by Moderna, with additional vaccines in
development. All of these vaccines
target the original 2019-nCoV-Wuhan
variant, and all but a few target primarily
its Spike protein.
Yet, as
the vaccines are undergoing deployment, several new virus variants
of tremendous concern have already emerged. Additional virus
variants will continue to emerge at an even faster rate because of
the widespread dissemination of the virus with many patient bodies
serving as virus factories providing historically the biggest ever
opportunities for the virus to escape existing vaccines and
antibody drugs. Failure of vaccines and antibody drugs is therefore
certain; the only question is how long will it be before the
vaccines
become substantially ineffective.
Replacing
current vaccine with a new vaccine, as has been suggested, would be
an endless game of chasing a rapidly changing epidemic that would
be costly and also
would
remain substantially non-responsive
to the threat, since the virus will continue to remain many steps
ahead of the vaccine.
It is
well known that viruses, particularly RNA viruses, mutate rapidly,
and that such changes produce "variants"
that
can
escape
from vaccines as well as from antibody
drugs. SARS-CoV-2 has a repair mechanism that retains some fidelity
during reproduction, and therefore it changes less rapidly than
Influenza A viruses or HIV. Nevertheless, given the significant
penetration of the virus into human population, and the
very high viral loads achieved in severe cases of the
infection, the virus has a
huge opportunity to change. Additional virus variants will
undoubtedly continue to emerge at an even faster rate because of
the widespread dissemination of the virus through
many patients, their bodies effectively serving as
"factories".
This important concern, voiced by several eminent scientists, has
not been regarded with the seriousness it deserves by supporting
and enabling rapid regulatory development of broad-spectrum
anti-coronavirus drugs.
The world
has already witnessed at least five important SARS-CoV-2 variants
with significant impact, as a result of the large number of persons
becoming infected. The very first important variant, namely D614G,
replaced the original Wuhan strain completely and rapidly during
the first wave of the pandemic itself. In the current second wave,
we have seen emergence of the lineage B.1.1.7 variant from United
Kingdom (Kent and London), the N501Y-V.2 (also called
lineage B.1.351) from South
Africa, and the P.1 variant (also called lineage B.1.1.248) from
Brazil. California has seen lineage B.1.429 /(CAL.20C) variant
become dominant in Los Angeles county recently, with over 50% of
the infections. It appears to be replacing the earlier
dominant CAL.20G variant. Several additional
variants have been identified. New variants continue to be
identified at a rapid pace as viral genome sequencing efforts are
accelerated.
Each of
these five variants arose
independently and in
distinct geographic areas, and yet they share many common features,
including a number of mutations in the receptor-binding region of
the coronavirus Spike protein. It appears that the 501Y mutation in
the spike protein leads to stronger binding to the
human cellular receptor ACE2, allowing the virus to infect more
productively, and has become more
common in later variants. It appears that the
E484K mutation, along with other mutations, present in the South
African and Brazilian variants, may result in
escape from vaccines and antibodies.
A major
concern is the fact that the variants that are now becoming
dominant have an accumulation of multiple mutations. This is
predictive of such variants being more resistant to drugs and
vaccines. They are likely to have been selected against drug
pressure or immune system pressure, and thus would likely have
resistance to antibody drugs, as well as other commonly used
drugs, as suggested by
eminent scientists. Further, it is now
known that some of the new variants can
cause infection of a previously recovered coronavirus patient, and
sometimes may lead to more severe disease than the earlier
infection. Such
new
variants can be logically expected to be resistant to antibodies as
well as vaccines. Additionally, it
has already been found or suspected that many of the new variants
are or are expected to be resistant to existing antibody drugs.
Given the known weak effectiveness of available antibody drugs,
even a small resistance would likely allow a variant to escape
the current antibody drugs.
Of note,
the currently approved drugs, namely remdesivir, the Regeneron
antibody cocktail, or the Eli Lilly single antibody drug, had
demonstrated only moderate effectiveness in clinical trials.
Remdesivir reduced the length to recovery in severe disease cases
in hospitalized patients by approximately six days, from 18 days to
12 days in a clinical trial,
NIAID ACIT-1, reported in its European (CHMP) Product
Information. The Regeneron drug
dosing in a clinical trial was at
2.4g or
8g of
total antibody, while the Eli Lilly antibody drug dose in the
combination therapy clinical trial was at 5.6g, although single
antibody therapy dosages from 700mg upwards are also being
evaluated. These high dosage levels are indicative of
relatively weak effectiveness. The U.S. Food and Drug
Administration (FDA) has granted Emergency Use Authorization (EUA)
for the Regeneron REGN-COV-2 cocktail, and also to a Eli Lilly
single antibody bamlanivimab (LY-CoV555) with both
authorizations restricted to
the treatment of mild to moderate COVID-19 only. Thus, further loss
of effectiveness of the existing drugs as new variants emerge would
have devastating consequences.
Vaccines,
it is now clearly apparent, are neither the great hope nor panacea
that the scientific community had once thought for this pandemic.
The South African variant, 501Y.v2 is of great concern as
scientists believe it may escape current vaccines. Its mutations
are also shared by the Brazilian variant, P.1.
Vaccinated persons coming down
with SARS-CoV-2 infection has already been witnessed. As more
variants emerge, existing vaccines would very likely lose
effectiveness. An
additional concern is that some of the variants are expected to
result in greater total fatality numbers. A more
contagious variant would cause more number of cases and thus
greater number of fatalities. A more lethal variant would lead to a
greater proportion of infected patients dying (i.e. a greater case
fatality rate). The UK B.1.1.7 variant is currently estimated by
the UK scientific advisory body, namely New and Emerging
Respiratory Virus Threats Advisory Group (NERVTAG), to be highly
contagious (transmissible), infectious, and more lethal than
previous variants.
The
SARS-CoV-2 virus, despite
its
current and future variants, is extremely unlikely
to escape a broad-spectrum anti-coronavirus drug like the one being
developed by NanoViricides. This is in complete
contrast with drugs based on antibodies, antibody cocktails, as
well as with preventative
vaccines.
NanoViricides has
been developing broad-spectrum anti-coronavirus drug candidates
since the early reports of the new virus from China, then known as
2019-nCoV. We were able to
bootstrap this development using our knowledge gained in the
earlier endeavors working on SARS-CoV-1 and MERS
coronaviruses.
NanoViricides has
been able to conduct this novel drug development at an accelerated
pace because of the benefits of its platform technology. We were
able to bootstrap our SARS-CoV-2 drug development efforts using the
c-GMP-compatible manufacturing processes developed for our then
flagship NV-HHV-101 drug candidate
for shingles dermal treatment. Further, NanoViricides has a
tremendous advantage in that the Company has its own cGMP-capable
manufacturing facility in Shelton, CT. This facility is capable of
producing approximately 4kg of the COVID-19 drug per batch. We
anticipate that this scale would be sufficient for human clinical
trials, and possibly for initial introduction under Compassionate
Use, Emergency Use Authorization or similar regulatory
approval.
"We are
well poised and are advancing the fight against the
coronaviruses with a weapon that has perhaps the best
characteristics for succeeding in taming this
pandemic," said Anil R. Diwan,
PhD, President and co-Founder of NanoViricides, Inc., and
co-Inventor of its platform technologies and drug
candidates.
About NanoViricides
NanoViricides, Inc.
(the "Company")(www.nanoviricides.com)
is a development stage company that is creating special
purpose
nanomaterials for antiviral therapy. The Company's novel
nanoviricide® class of drug
candidates are designed to specifically attack enveloped virus
particles and to dismantle them. Our lead drug candidate is
NV-HHV-101 with its first indication as dermal topical cream
for the treatment of shingles rash. In addition, we are developing
a clinical candidate for the treatment of COVID-19 disease caused
by SARS-CoV-2 coronavirus. The Company cannot project an exact date
for filing an IND for this drug because of its
dependence on a number of external collaborators and
consultants.
The
Company is now working on performing required safety pharmacology
studies and completing an IND application. The Company believes
that since remdesivir already is US FDA approved, our drug
candidate encapsulating remdesivir is likely to be an approvable
drug, if safety is comparable. Remdesivir is developed by Gilead.
The Company has developed our own drug candidates
independently.
The
Company intends to re-engage into an IND application to
the US FDA for NV-HHV-101 drug candidate for the treatment of
shingles once its COVID-19 project moves into clinical trials,
based on resources availability. The NV-HHV-101 program was slowed
down because of the effects of recent COVID-19 restrictions, and
re-prioritization for COVID-19 drug development work.
The
Company is also developing drugs against a number of viral diseases
including oral and genital Herpes, viral diseases of the eye
including EKC and herpes keratitis, H1N1 swine
flu,
H5N1 bird flu, seasonal Influenza, HIV, Hepatitis C, Rabies, Dengue
fever, and Ebola virus, among others.
NanoViricides' platform technology
and programs are based on the TheraCour® nanomedicine
technology of TheraCour, which TheraCour licenses from
AllExcel. NanoViricides
holds a worldwide exclusive perpetual license to this technology
for several drugs with specific targeting mechanisms in perpetuity
for the treatment of the following human viral diseases: Human
Immunodeficiency Virus (HIV/AIDS), Hepatitis B Virus (HBV),
Hepatitis C Virus (HCV), Rabies, Herpes Simplex Virus (HSV-1 and
HSV-2), Varicella-Zoster Virus (VZV), Influenza and Asian Bird Flu
Virus, Dengue viruses, Japanese Encephalitis virus, West Nile Virus
and Ebola/Marburg viruses. The Company has executed a
Memorandum of Understanding with TheraCour that provides a limited
license for research and development for drugs against human
coronaviruses. The Company intends to obtain a full license and has
begun the process for the same. The Company's technology is based
on broad, exclusive, sub-licensable, field licenses to drugs
developed in these areas from TheraCour Pharma, Inc. The
Company's business model is
based on licensing technology from TheraCour Pharma Inc. for
specific application verticals of specific
viruses, as established at its foundation in 2005.
As is
customary, the Company must state the risk factor that the path to
typical drug development of any pharmaceutical product is extremely
lengthy and requires substantial capital.
As
with any drug development efforts by any company, there can be no
assurance that any of the Company's pharmaceutical
candidates would show sufficient effectiveness and safety for human
clinical development at this time. Further, there can be no
assurance at this time that
successful results against coronavirus in our lab will lead to
successful clinical trials or a successful pharmaceutical
product.
This
press release contains forward-looking statements that reflect the
Company's current expectation regarding future
events. Actual events could differ materially and substantially
from those projected herein and depend on a number of factors.
Certain statements in this release, and other written or oral
statements made by NanoViricides, Inc. are
"forward-looking statements"
within the meaning of Section 27A of the Securities Act of 1933 and
Section 21E of the Securities Exchange Act of 1934. You should not
place undue reliance on forward-looking statements since they
involve known and unknown risks, uncertainties and other
factors which are, in some cases, beyond the Company's control and
which could, and likely will, materially affect actual results,
levels of activity, performance or achievements. The Company
assumes no obligation to publicly update or revise these
forward-looking statements for any reason, or to update the reasons
actual results could differ materially from those anticipated in
these forward-looking statements, even if new information becomes
available in the future. Important factors that could cause actual
results to differ materially from the company's expectations
include, but are not limited to, those factors that are disclosed
under the heading "Risk Factors" and elsewhere in documents filed
by the company from time to time with the United States
Securities and Exchange Commission and other regulatory
authorities.
Although
it is not possible to predict or identify all such factors, they
may include the following: demonstration and proof of principle in
preclinical trials that a nanoviricide is safe and
effective; successful development of our product candidates; our
ability to seek and obtain regulatory approvals, including with
respect to the indications we are seeking; the successful
commercialization of our product candidates; and
market
acceptance of our products. FDA refers to US Food and Drug
Administration. IND application refers to "Investigational New
Drug" application. CMC refers to "Chemistry, Manufacture, and
Controls". CHMP refers to the
Committee for Medicinal Products for Human Use, which
is the European Medicines Agency's (EMA) committee responsible for
human medicines.
Contact:
NanoViricides,
Inc.
info@nanoviricides.com
Public
Relations Contact:
MJ
Clyburn
TraDigital
IR
clyburn@tradigitalir.com
Source:
NanoViricides,
Inc.