HOUSTON, May 27, 2020 /PRNewswire/ -- Moleculin Biotech,
Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical
stage pharmaceutical company with a broad portfolio of drug
candidates targeting highly resistant tumors and viruses, today
announced that the US Food and Drug Administration ("FDA") has
granted the Company's request for a Pre-IND Meeting to provide
guidance regarding the Company's plan to study its drug candidate,
WP1122, in a clinical trial for patients with COVID-19 (the disease
caused by the SARS-CoV-2 coronavirus). In addition, Moleculin
provided a general update on its WP1122 development efforts.
On May 1, 2020, Moleculin
submitted a request to the FDA for a Pre-IND Meeting to seek
guidance on requirements for submitting an Investigational New Drug
("IND") application to study its drug candidate, WP1122, in a
clinical trial for patients with COVID-19. On May 6, 2020, the FDA granted the Company's
meeting request, and indicated that its goal for providing written
responses is June 30, 2020, but that
it plans to act early on this meeting request, provided there are
no significant deficiencies in the Pre-IND package or unexpected
shifts in its work priorities. The FDA has created a special
emergency program for possible COVID-19 therapies that it calls the
Coronavirus Treatment Acceleration Program ("CTAP"). The FDA has
stated that CTAP uses every available method to move new treatments
to patients as quickly as possible, while at the same time finding
out whether they are helpful or harmful.
Given the toxicology testing plan discussed below, we estimate
that we should be able to submit our IND application in the second
half of this year. More specific timing will depend upon the
guidance we receive from our Pre-IND Meeting with the FDA.
"While we wait for guidance from the FDA, we have continued to
move forward with testing on multiple fronts," commented Moleculin
Chairman and CEO Walter Klemp.
"In that regard, it's helpful to understand the various goals for
preclinical testing. In the case of the research we
previously announced on March 17,
2020 being conducted at an outside university research
institution, this is essentially basic research into understanding,
on a molecular level, the mechanism of action of WP1122 as a 2-DG
prodrug and how that might affect SARS-CoV-2 and other viruses, as
well as aggressive tumor cells. Such research is longer-term
in nature and not required for our IND application, so it's not
part of our critical path for submitting an IND, and, if allowed by
the FDA, getting WP1122 into clinic." The Company has begun
supporting these research efforts by supplying drugs for testing
and funding for analytical aspects of collaborative studies.
The researchers are in the process of identifying the proper
virology research laboratory to begin testing WP1122 against
SARS-CoV-2 and/or other viruses.
In order to properly support the Company's planned IND
application, it has engaged ImQuest BioSciences ("ImQuest") and the
Illinois Institute of Technology Research Institute ("IITRI"), two
organizations focused on supplying the kind of contract research
support required for an IND submission. While IITRI is
initially focused on preclinical toxicology testing to help
determine whether WP1122 can be considered safe for testing in
humans, ImQuest is focused on supporting the scientific rationale
behind proposing WP1122 as a possible treatment for COVID-19.
On April 7, 2020, Moleculin
contracted with ImQuest for two rounds of preclinical assessment of
the potential for WP1122 to address COVID-19. The first step
was to demonstrate whether or not the improved pharmacology of
WP1122 gave it a greater therapeutic window than 2-DG, a compound
which was shown to stop replication of SARS-CoV-2 by an independent
research team at the Göethe-University of Frankfurt in a preprint of a research article
and also was previously shown to display antiviral activities in
other viruses. This first ImQuest step was done with a cell
viability assay comparing inhibition of virus-induced cytopathic
effects of 2-DG and WP1122 head-to-head in a human cell line
infected with a coronavirus. The second round was to
demonstrate the ability of WP1122 to inhibit coronavirus production
in mammalian cell culture. This was done using a virus yield
The testing done by ImQuest was performed on a surrogate of
SARS-CoV-2 called Human coronavirus strain 229E ("HCoV-229E")
because it was a validated assay immediately available at
ImQuest. Moleculin's scientific team and ImQuest consider
HCoV-229E to be an appropriate model for SARS-CoV-2 in particular
because one of the primary theoretical mechanisms of action ("MOA")
for both 2-DG and WP1122 is alteration of the glycoprotein/glycan
structures (spikes) that form on the outside shielding of the
virus, and the glycoprotein/glycan spikes present on HCoV-229E play
a similar function in the viral lifecycle to those on
SARS-CoV-2. As well, the other primary MOA of 2-DG/WP1122 is
the inhibition of glycolysis and the HCoV-229E surrogate has a
similar dependence on glucose/mannose metabolism.
Although these in vitro results should not be considered
conclusive or indicative of what will happen in vivo, the initial
results received on May 4, 2020 show
that both 2-DG and WP1122 have an antiviral effect on
HCoV-229E. WP1122 displayed a greater therapeutic index than
2-DG, while the virus yield reduction assay demonstrated a 5 to
10-fold inhibition of coronavirus production by WP1122 and 2-DG
when compared to untreated virus control.
"While we consider these initial results to be positive, one of
the important things we have learned is that testing of 2-DG and
WP1122 in vitro can be more challenging than testing of other
drugs, like Remdesivir, for example." added Mr. Klemp. "This
is mainly because available testing methods often use significantly
different concentrations of natural glucose in the cell culture
medium and these tests can be based on very different human host
cells. 2-DG and WP1122 are designed to directly affect
glucose metabolism, therefore tests using widely different levels
of glucose in the media and use of cells with different glucose
dependence can lead to significantly different results.
We will be placing increased focus on the development of a
standardized procedure to test this new class of agents, along with
determination of appropriate levels of growth media glucose and
selection of the most appropriate human host cells for in vitro
assays of WP1122 and related agents."
Out of an abundance of caution, the Company requested ImQuest
repeat their tests to provide additional confidence in their
findings, and, as such, the Company cautions readers not to rely on
these initial results. In addition to having ImQuest repeat
their tests, the Company is arranging for additional in vitro
testing to include additional human cell lines and the use of a
validated SARS-CoV-2 assay, as well as testing against other
pathogenic viruses, all with the intent of increasing the strength
of the basic scientific rationale.
Mr. Klemp concluded: "It's also worth remembering that an
additional benefit of the IND-enabling work we are doing for WP1122
for the possible treatment of patients with COVID-19 is that this
also supports the necessary work for an IND for WP1122 for the
potential treatment of patients with other viral infections or
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
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 include,
without limitation, whether the results of subsequent testing will
statistically support the initial ImQuest results, the Company's
ability to file an IND in the second half of 2020, and whether
additional testing will continue to support the potential for
WP1122 to become a treatment for COVID-19 or other 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.
/ Carol Ruth
The Ruth Group
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SOURCE Moleculin Biotech, Inc.