
Significantly Improved Safety
Profile and Metabolism of Remdesivir Observed Due to Encapsulation
in NanoViricides Drug Candidate Enabling Potential Highly Effective
Pan-Coronavirus Antiviral Drug
Shelton, Connecticut --
September 22, 2021 -- InvestorsHub NewsWire -- 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.
Contact:
NanoViricides, Inc.
info@nanoviricides.com
Public Relations Contact:
MJ Clyburn
TraDigital IR
clyburn@tradigitalir.com
Source: NanoViricides,
Inc.