SHELTON, Conn., Sept. 22, 2021 /PRNewswire/
-- NanoViricides, Inc. (NYSE American: NNVC) (the
"Company"), a leader in the development of highly effective
antiviral therapies based on a novel nanomedicines technology,
reported today on the significant advantages gained by remdesivir
encapsulation within its lead COVID-19 candidate NV-CoV-2 thereby
resulting in the dual-acting drug candidate NV-CoV-2-R with the
promise of a potential pan-coronavirus cure.
Pharmacokinetics of Encapsulated Remdesivir Compared to Standard
Formulation
Almost double the amount of remdesivir remained intact in plasma
when given as the encapsulated NV-CoV-2-R form, in comparison to
the standard remdesivir formulation made in betadex sulfobutyl
ether sodium (SBECD), during the first day of dosing in a rat
pharmacokinetics study. Additionally, remdesivir accumulation was
observed on repeated dosing of NV-CoV-2-R. After the fifth dose of
NV-CoV-2-R (on day 7), in comparison to the standard remdesivir
dosing pattern (twice on day 1 followed by daily thereafter; on day
7), the circulating level of intact remdesivir in plasma was 75%
greater in the NV-Cov-2-R group as compared to the standard
remdesivir group. The data were normalized to reflect the same
amount of remdesivir given to the animals per kg body weight for
uniform comparison. The assays were performed using the
well-established isotopic internal standard method of remdesivir
estimation with LCMS detection.
The increased circulating level of intact remdesivir when given
as NV-CoV-2-R encapsulated formulation without any increase in
toxicity is significant. It can be expected to result in improved
antiviral effectiveness of the remdesivir component in human usage
of NV-CoV-2-R treatment. This is important because remdesivir is a
highly effective drug in cell culture and pre-clinical studies but
does not show clinical effectiveness in humans at levels that
would be expected based on its cell culture efficacy because of its
rapid metabolism. Additionally, there is very little margin to
increase remdesivir dosing in its standard formulation because of
dose limiting toxicity.
NV-CoV-2-R was found to be less toxic than the standard
remdesivir formulation in this study. At day 7, when a total of
80mg/kg remdesivir was dosed in the standard formulation, the body
weight loss was approximately 9.5% in male and 9.5% in female
animals. In contrast, when 80mg/kg of remdesivir was delivered as
NV-CoV-2-R encapsulated formulation, at day 7, the weight loss was
only approximately 3% in male animals and 1% in female animals
which was the same as with the vehicle treatment reflecting
injection trauma itself and no drug toxicity.
These data demonstrate that the pan-coronavirus nanoviricide
drug candidate NV-CoV-2-R substantially decreases the loss of
remdesivir to bodily metabolism in comparison to the standard
formulation. The Company anticipates that this stabilizing effect
should lead to a highly effective pan-coronavirus drug that could
potentially cure most cases of COVID-19 infection.
Both remdesivir and NV-CoV-2 have demonstrated broad-spectrum
activity against coronaviruses. Thus NV-CoV-2-R is expected to
continue to be active in spite of evolution of novel variants of
SARS-CoV-2. In contrast, antibody drugs and vaccines which
induce antibodies lose effectiveness against variants. The more the
variant drifts from the original strain, the less protection is
offered by vaccines, and effectiveness of antibodies also
diminishes significantly. This is now known to be occurring for
current vaccines and antibodies during the global COVID-19
pandemic.
NV-CoV-2-R combines (1) the power of the nanoviricides®
platform attacking the virus particle outside cells with (2) the
power of remdesivir in attacking the virus reproduction inside
cells. Additionally, we believe that (3) NV-CoV-2-R would be
improving the effect of remdesivir by (a) enabling a higher
effective concentration of remdesivir in the body and (b)
sustaining this higher concentration for a substantially longer
period of time, both compared to the standard formulation of
remdesivir, as observed in this pharmacokinetic animal study.
NV-CoV-2-R combines two different mechanisms of attack against
the virus and therefore is expected to be substantially more
difficult for the virus to evade than either NV-CoV-2 or remdesivir
alone. This is important because scientists believe it is only a
matter of time before variants of SARS-CoV-2 that evade current
vaccines and antibody drugs become commonplace.
Both NV-CoV-2 and remdesivir are expected to retain their
effectiveness against variants of SARS-CoV-2. NV-CoV-2 has shown
effectiveness against multiple unrelated coronavirus types.
Remdesivir has been demonstrated to possess antiviral activity in
cell culture against a large number of RNA viruses.
The standard Veklury® formulation of remdesivir in betadex
sulfobutyl ether sodium (SBECD) helps with suspending remdesivir in
solution, but does not appear to significantly improve upon the
metabolic effects. In contrast, NV-CoV-2-R is an encapsulation
approach wherein remdesivir would slowly leak out into the
bloodstream from the polymeric nano-micelle over time, imparting
protection against metabolism and sustained effective levels of the
encapsulated drug component over a longer time period.
"We are pleased to report that NV-CoV-2-R encapsulation of
remdesivir indeed provided substantially superior pharmacokinetics
as per our expectation in designing this drug," said Anil R. Diwan,
Ph.D., President and Chairman of the Company, adding, "We believe
our drug candidate NV-CoV-2-R is promising to result in a
pan-coronavirus cure if successful in clinical trials."
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. We are
developing clinical candidates for the treatment of COVID-19
disease caused by SARS-CoV-2 coronavirus. Our other lead drug
candidate is NV-HHV-101 with its first indication as dermal topical
cream for the treatment of shingles rash. In addition, the Company
has several antiviral programs in various pre-clinical stages.
The Company is now working on tasks for completing an IND
application for its COVID-19 drug candidates. 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 currently pursuing two separate drug
candidates for the treatment of COVID-19 patients. NV-CoV-2 is our
nanoviricide drug candidate that does not encapsulate remdesivir.
NV-CoV-2-R is our other drug candidate that is made up of NV-CoV-2
with remdesivir encapsulated in it. The Company believes that since
remdesivir is already 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 both of its own drug candidates NV-CoV-2 and
NV-CoV-2-R 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
Coronavirus infections, 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'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 at this time that any of the Company's pharmaceutical
candidates would show sufficient effectiveness and safety for human
clinical development. 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
that 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. cGMP refers to
current Good Manufacturing Practices. 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.