SHELTON, Conn., April 9,
2019 /PRNewswire/ -- NanoViricides, Inc. (NYSE American: NNVC)
(the "Company") a company with novel platform technology to treat
difficult and life-threatening viral diseases, reports that US FDA
has responded to its request for a pre-IND meeting. In addition,
the Company reports that it has completed production of the drug
product for the ensuing GLP Safety/Toxicology studies of its lead
drug candidate in the HerpeCide™ program.
The Company reports that it has successfully completed the
scale-up of the chemistries and production of kg-scale quantities
of the drug substance or API, NV-HHV-101. The Company further
reports that it has successfully scaled up and manufactured about
10kg of the drug product, as required for the ensuing GLP
Safety/Toxicology ("Tox Package") studies. The production of the
drug product, a dermal topical skin cream formulation of the API
was at different API concentrations as required for the study. All
of the production, including that of the API and of the drug
products at various API concentrations, was performed under
stringent conditions meeting regulatory requirements for the GLP
Tox Package study.
The entire production was accomplished at the Company's own
cGMP-capable manufacturing facility at Shelton, CT. The Company has now demonstrated
that it has multi-kilogram per batch drug production
capability.
The GLP Safety/Toxicology study is scheduled to begin in the
second week of May at BASi, Evansville,
IN, a Contract Research Organization that is specialized in
IND-enabling safety/toxicology studies.
The Company also reports that it is preparing the pre-IND
Meeting Submission Documents as required by the US FDA. The Company
is developing its clinical program and these submission documents,
for NV-HHV-101, formulated as a skin cream for topical application,
with the help of regulatory affairs experts from the Biologics
Consulting Group, Inc., Alexandria,
VA.
The FDA has responded to our pre-IND meeting request letter and
has asked for the documents to be submitted by April 29th. In addition, consistent with current
protocol, the FDA has stated that they will provide a written
response to the Company's submission. This written response will
guide the Company's IND submission for this drug candidate and
indication.
The present indication for NV-HHV-101 is for the treatment of
shingles rash caused by reactivation of the shingles virus, VZV
(varicella-Zoster-Virus). VZV causes chickenpox in children as a
result of primary infection, and then becomes latent. Reactivation
occurs in adulthood when immune surveillance weakens, due to age,
stress, or other immune-compromising factors, including other
diseases.
The Company is also developing drugs against HSV-1 "cold sores"
and HSV-2 "genital ulcers", both based on this same drug candidate,
although final clinical candidates are in pre-clinical optimization
stage for both of these indications as of now.
The Company recently reported that its first broad-spectrum drug
candidate in the HerpeCide™ program, namely, NV-HHV-101, has
successfully completed the non-GLP portion of the Safety/Toxicology
studies that are required for filing an IND in order to initiate
human clinical trials.
NV-HHV-101 is a broad-spectrum nanomedicine designed to attack
herpesviruses that use the HVEM ("herpesvirus entry mediator")
receptor on human cells. This drug candidate is composed of a
flexible polymeric micelle "backbone" to which a number of small
chemical ligands are chemically attached. The ligands in this case
are designed to mimic the binding site of the herpesviruses on
HVEM, based on molecular modeling. NV-HHV-101 is expected to bind
to VZV via a number of binding sites (i.e. the ligands), thereby
encapsulating the virus particle and destroying its ability to
infect human cells. This "Bind, Encapsulate, Destroy" nanoviricide®
strategy is distinctly different from the mechanism of action of
existing antiviral drugs against VZV.
The Company has conducted a drug candidate optimization program
using an ex vivo human skin organ culture ("SOC")
model of VZV infection, together with cell culture based VZV
infection studies, to arrive at NV-HHV-101. The SOC model of VZV
infection has been developed by Professor Jennifer Moffat at the Upstate Medical Center,
SUNY, Syracuse, NY. It is the only
pre-clinical model suitable for evaluating a topical therapy
against shingles because VZV infects only humans. There is no
animal model available for the evaluation of topical drugs against
VZV infection.
NV-HHV-101 is formulated as a dermal cream to be applied
topically on the rash. It is expected to reduce viral load at the
site, thereby arresting the progress of the shingles rash, and
minimizing damage to nerve endings in the area. It is generally
believed that the damage to nerve endings caused by VZV that is
replicated locally after it is released from the nerves initially
leads to the severe "pins-and-needles" debilitating pain of
shingles. Thus NV-HHV-101 is expected to minimize the entire
pathology of shingles, including the rash, skin damage, nerve
damage, and associated pain. The Company intends to focus the
initial clinical studies to evaluate the effect of application of
NV-HHV-101 on the shingles rash.
Existing antivirals against VZV include oral derivatives of
acyclovir. These drugs requires activation by a viral enzyme,
thymidilate kinase (vTK), for further cellular conversion to the
active triphosphate form that interferes with the viral DNA
polymerase. However, the vTK encoded by VZV has an extremely poor
activity (compared to vTK from HSV-1 or HSV-2), and thus these
drugs have very poor activity against VZV, and large oral dosages
over extended periods are needed to be given for relatively small
clinical benefit. Additionally, a dermal topical cream formulation
of cidofovir is employed in very severe cases of shingles.
Cidofovir is highly toxic, particularly towards kidneys. A safer,
effective, drug is thus an unmet medical need for VZV.
Zostavax and other attenuated VZV (Oka strain) vaccines for
chickenpox are available, but not widely adopted. These vaccines
may lead to a less severe form of shingles in adulthood or at a
later age ("rebound shingles"), compared to the "wild type"
chickenpox virus. A new vaccine, Shingrix® has been introduced by
GSK recently, based on subunits or protein fragments of the virus,
which cannot lead to such rebound shingles, but suffers from a very
severe side effects profile. Shingrix is not yet widely available,
potentially due to difficulties in manufacturing.
The market size for a highly effective drug against shingles is
projected to be in several billions of dollars, if it leads to
substantial reduction in the advanced manifestation of the disease,
namely PHN, by independent consultants. These market size estimates
account for the effect of ZostaVax and the newly introduced
Shingrix vaccine on the patient population size. PHN or
"post-herpetic neuralgia" is the continuation of the debilitating
pain of shingles well after the patient has recovered from the
shingles rash episode itself. PHN is believed to be due to
extensive damage to nerve endings in the area of the shingles rash,
and is expected to be correlated with the severity of the shingles
presentation (or viral load). A less effective drug that minimizes
the pathology of the shingles rash alone is also projected to have
a market size into a billion dollar range.
The Company also continues to evaluate this broad-spectrum drug
candidate as well as certain variations based on the same
candidate, for the treatment of other herpesviruses, namely HSV-1
cold sores and HSV-2 genital herpes. The market size for our
immediate target drugs in the HerpeCide™ program is variously
estimated into tens of billions of dollars. The Company believes
that its dermal topical cream for the treatment of shingles rash
will be its first drug heading into clinical trials. The Company
believes that additional topical treatment candidates in the
HerpeCide™ program, namely, HSV-1 "cold sores" treatment, and HSV-2
"genital ulcers" treatment are expected to follow the shingles
candidate into IND-enabling development and then into human
clinical trials.
About NanoViricides
NanoViricides, Inc. (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. The Company is developing drugs
against a number of viral diseases including H1N1 swine flu, H5N1
bird flu, seasonal Influenza, HIV, oral and genital Herpes, viral
diseases of the eye including EKC and herpes keratitis, Hepatitis
C, Rabies, Dengue fever, and Ebola virus, among others. 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 refers to
investigational drug application. API refers to active
pharmaceutical ingredient.
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SOURCE NanoViricides, Inc.