HOUSTON, June 16, 2020 /PRNewswire/ -- Moleculin Biotech,
Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical
stage pharmaceutical company with a broad portfolio of drug
candidates, today announced that a repeat of previous in vitro
testing has corroborated the antiviral potential of WP1122.
Although developing in vitro data is an initial step and the
data may not necessarily reflect the antiviral effects in vivo, the
results of this repeated round of in vitro testing received on
June 1, 2020, confirm that WP1122 has
an antiviral effect on Human Coronavirus 229E ("HCoV-229E"), a
surrogate of SARS-CoV-2, the virus responsible for
COVID-19.
"We felt it was important to confirm these results," commented
Walter Klemp, Chairman and CEO of
Moleculin, "so, out of an abundance of caution, we had an
independent testing contractor run them a second time. While
the results are encouraging, we believe, based on guidance from the
FDA, we will need additional studies to further assess WP1122's
antiviral capability, and consistent with our previous guidance, we
will continue to push forward with additional in vitro and in vivo
testing with the goal of a possible IND filing by the end of 2020,
in preparation for beginning a human clinical trial
thereafter."
The guidance provided thus far by the Company has been that it
expects to file its request for Investigational New Drug (IND)
status to test WP1122 for the treatment of COVID-19 patients during
the second half of 2020. The opportunity to shorten that time
frame may depend on the Company's ability to use non-GLP (studies
not done in strict adherence to "Good Laboratory Practices")
toxicology data for the IND submission and exploring this
possibility was a part of the Company's request for feedback in its
Pre-IND submission to the US Food and Drug Administration,
("FDA"). Based on the FDA's response, Moleculin now plans to
present its non-GLP toxicology, when available, to the FDA in a
second Pre-IND meeting request. While there can be no
assurance that the FDA will allow Moleculin's IND to go into effect
on the basis of non-GLP toxicology data, the Company believes the
possibility is worth pursuing, because it could significantly
reduce its timeline to begin clinical trials for WP1122.
On May 27, 2020, Moleculin
announced results from the initial preclinical assessment of the
potential for WP1122 to address COVID-19. The testing
involved a cell viability assay, followed by a virus yield
reduction assay. These tests were intended to assess and
compare in vitro antiviral properties of WP1122 and its active
moiety (subpart) 2-DG. In this regard, an unedited version of
an article that has now been accepted for publication in the
scientific journal, Nature (Bojkova, D. et al. Proteomics of
SARS-CoV-2-infected host cells reveals therapy targets, Nature
https://doi.org/10.1038/s41586-020-2332-7 2020), reports that one
of the therapeutic targets in SARS-CoV-2 is glycolysis. This work
performed by an independent research team at the Göethe-University
of Frankfurt further showed that
targeting glycolysis with 2-DG stopped replication of SARS CoV-2 in
vitro. These results are consistent with previous research
reports demonstrating the antiviral activities of 2-DG in other
viruses. Notwithstanding the available preclinical data, the
Company believes that, without the benefit of WP1122's prodrug
structure, 2-DG's rapid metabolism and limited drug-like properties
prevent it from being sufficiently effective in vivo and that in
vivo testing of WP1122 may make its benefits more apparent.
The Company's testing was intended to demonstrate the ability of
WP1122, a prodrug of 2-DG, to inhibit coronavirus proliferation in
a mammalian cell culture. The testing was performed using a
surrogate of SARS-CoV-2 called HCoV-229E, which was a validated
assay that was immediately available at the time. Moleculin
and the independent testing contractor consider HCoV-229E an
appropriate surrogate model for SARS-CoV-2 as both 2-DG and WP1122
are thought to act as both inhibitors of glycolysis and also by
altering glycoprotein/glycan structures, including the
characteristic spikes found on SARS-CoV-2. Glycans have been shown
to form on the outside of the virus and can serve to shield it from
the host's immune system. Additionally, the glycoprotein/glycan
spikes present on HCoV-229E and on SARS-CoV-2 appear to perform
similar functions in the viral lifecycle. Moreover, 2-DG and
WP1122 are also believed to work by inhibiting glycolysis, which is
expected to play a similar role in HCoV-229E as it does in
SARS-CoV-2.
The initial tests were intended to provide comparative data, and
therefore were done with both WP1122 and 2-DG. The follow-on
tests just completed were intended to confirm the antiviral
activity of WP1122, and therefore tested only WP1122.
Additionally, the results of in vitro testing thus far lead the
Company to believe that conventional methods of antiviral testing
were not designed to test the class of agents represented by 2-DG
and WP1122 and testing methods should be optimized to reflect the
full antiviral potential of these sugar antimetabolites. The
mechanism of action of 2-DG and WP1122 is very different from other
drugs being developed for COVID-19. Specifically, because
2-DG has been shown to target glucose metabolism, in vitro testing
results are significantly affected by the concentration of natural
glucose in the microenvironment present during viral replication
and continued infection. For this reason, and consistent with
guidance from the FDA, the Company will seek to evaluate WP1122 in
an animal model for COVID-19 as a part of its IND preparation.
As previously announced, on May 1,
2020, Moleculin submitted a Pre-IND meeting request with the
FDA regarding the clinical development of WP1122 for the treatment
of COVID-19. On June 2, 2020,
the Company received the FDA's written response with guidance
regarding application of the agency's requirements for clinical
development programs in this circumstance.
Regarding the FDA's Pre-IND response, Walter Klemp stated, "The swift response from
the FDA will help shape our planned pathway for the pre-clinical
work necessary for an IND. This includes further in vitro analysis,
as well as animal testing to demonstrate sufficient antiviral
potential and develop sufficient safety data to support allowing
WP1122 to be tested in humans for the treatment of COVID-19."
As already noted, the Company plans to address the FDA's
guidance, both in a second Pre-IND meeting and in an IND submission
currently anticipated for the end of 2020. The Company will
seek to conduct a Phase 1a/1b
proof-of-concept study, with the Phase 1b being in a relatively small number of early,
mild COVID-19 patients.
About Moleculin Biotech, Inc.
Moleculin Biotech, Inc. is a clinical stage pharmaceutical
company focused on the development of a broad portfolio of oncology
drug candidates for the treatment of highly resistant tumors and
viruses. The Company's clinical stage drugs are: Annamycin, a Next
Generation Anthracycline, designed to avoid multidrug resistance
mechanisms with little to no cardiotoxicity, being studied for the
treatment of relapsed or refractory acute myeloid leukemia, more
commonly referred to as AML; WP1066, an Immune/Transcription
Modulator capable of inhibiting p-STAT3 and other oncogenic
transcription factors while also stimulating a natural immune
response, being studied for brain tumors, pancreatic cancer and
hematologic malignancies; and WP1220, an analog to WP1066, being
studied for the topical treatment of cutaneous T-cell lymphoma.
Moleculin is also engaged in preclinical development of additional
drug candidates, including additional Immune/Transcription
Modulators, as well as compounds capable of
Metabolism/Glycosylation Inhibition, such as WP1122.
For more information about the Company, please
visit http://www.moleculin.com.
Forward-Looking Statements
Some of the statements in this release are forward-looking
statements within the meaning of Section 27A of the Securities Act
of 1933, Section 21E of the Securities Exchange Act of 1934 and the
Private Securities Litigation Reform Act of 1995, which involve
risks and uncertainties. Forward-looking statements in this press
release include, without limitation, the ability of WP1122 to show
sufficient antiviral potential in an animal model, the ability of
Moleculin to file an IND submission by the end of 2020 and the
ability of WP1122 to be shown safe and effective for the treatment
of COVID-19 or other viral diseases. Although Moleculin believes
that the expectations reflected in such forward-looking statements
are reasonable as of the date made, expectations may prove to have
been materially different from the results expressed or implied by
such forward-looking statements. Moleculin Biotech has attempted to
identify forward-looking statements by terminology including
''believes,'' ''estimates,'' ''anticipates,'' ''expects,''
''plans,'' ''projects,'' ''intends,'' ''potential,'' ''may,''
''could,'' ''might,'' ''will,'' ''should,'' ''approximately'' or
other words that convey uncertainty of future events or outcomes to
identify these forward-looking statements. These statements are
only predictions and involve known and unknown risks,
uncertainties, and other factors, including those discussed under
Item 1A. "Risk Factors" in our most recently filed Form 10-K filed
with the Securities and Exchange Commission ("SEC") and updated
from time to time in our Form 10-Q filings and in our other public
filings with the SEC. Any forward-looking statements
contained in this release speak only as of its date. We undertake
no obligation to update any forward-looking statements contained in
this release to reflect events or circumstances occurring after its
date or to reflect the occurrence of unanticipated events.
Contacts
James Salierno
/ Carol Ruth
The Ruth Group
646-536-7028 /
7000
jsalierno@theruthgroup.com
cruth@theruthgroup.com
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SOURCE Moleculin Biotech, Inc.