Annamycin demonstrated to be a more potent
inhibitor of topoisomerase II-alpha and II-beta while remaining
inactive against established cardiomyocyte cultures
Results clearly aligned with lack of
drug-related cardiotoxic events in patients treated with
Annamycin in ongoing clinical trials; 100% of Annamycin subjects in
multiple studies (N=82) continue to show no signs of cardiotoxicity
during study
A prominent treatment for many adult cancers
and approximately 50% of all pediatric cancer patients are treated
with a cardiotoxic anthracycline
Annamycin composition of matter patent issued
April 9th; Patent enables
expansion into greater patient populations where cardiotoxicity
remains an unmet need
HOUSTON, April 10,
2024 /PRNewswire/ -- Moleculin Biotech,
Inc., (Nasdaq: MBRX) (Moleculin or the Company), a
clinical stage pharmaceutical company with a broad portfolio of
drug candidates targeting hard-to-treat tumors and viruses, today
announced positive preclinical data regarding the Company's
next-generation anthracycline, Annamycin, was presented at the
American Association for Cancer Research (AACR) Annual Meeting,
taking place April 5-10, 2024 in
San Diego, CA.
The poster titled, Non-cardiotoxic Properties of Annamycin, a
Clinically Evaluated Anthracycline and Potent Topoisomerase 2β
Poison, was presented in the "Late-Breaking Research:
Experimental and Molecular Therapeutics 2" session held on
Monday, April 8th. The
presented poster outlined results from the assessment and
comparison of the potency of doxorubicin (a commonly prescribed
anthracycline) and Annamycin, Moleculin's next-generation
anthracycline, against topoisomerase II-alpha and II-beta and
determine their impact on physiology of human cardiomyocytes
demonstrating no pathologic changes in mice hearts following
chronic in vivo exposure.
"Cardiotoxicity continues to be a significant side effect
limiting the clinical use of anthracyclines, despite anthracyclines
representing some of the most important treatments available for
AML and Advanced STS. These data, documenting lack of
cardiotoxicity of Annamycin and aligned with the data demonstrated
to date in our ongoing clinical trials, bolster our confidence in
Annamycin potential to offer patients a safe and effective
treatment option. Interestingly, the presented data demonstrates
that Annamycin appears to be a significantly more potent inhibitor
of topoisomerase II-beta than doxorubicin providing validation for
additional studies to reevaluate the role of topoisomerase II-beta
in anthracycline induced cardiotoxicity," commented Walter Klemp, Chairman and Chief Executive
Officer of Moleculin.
"Additionally, with our recently issued patent, which covers
composition of matter protection across all indications, we have
the potential to expand the development of Annamycin into greater
patient populations in indications where cardiotoxicity remains a
significant unmet need. We remain highly encouraged by Annamycin
and committed to advancing its development," concluded Mr.
Klemp.
As part of the presented data, the potency of Annamycin and
doxorubicin to inhibit topoisomerase II was tested in DNA
relaxation assays using recombinant topoisomerase II-alpha and
II-beta with kinetoplast as the DNA substrate. Annamycin and
doxorubicin cytotoxicity was assessed in a panel of cancer cell
lines cardiomyocytes (murine and human). In addition, the effects
on cardiomyocyte physiology (beating rate, contraction, electric
potential,) were assessed in human cardiomyocytes using the
xCELLigence RTCA CardioECR. The pathophysiology of the heart after
chronic exposure to the drugs was also evaluated in mice
models.
Key Data Highlights:
- Annamycin demonstrated to be a more potent topoisomerase
II-alpha and II-beta poison than doxorubicin.
- In contrast to doxorubicin:
-
- Annamycin does not affect viability of established culture of
human iPSCc cardiomyocytes (tested up to 1.5 μM)
- Annamycin does not affect contractility or the electric
potential of the cardiomyocytes
- Rat cardiomyocytes (H9c2) appear to be resistant to ANN
while sensitive to DOX
- Annamycin is well tolerated by the animals even at schedules
exceeding the therapeutic dosage while ex vivo pathology
examination of the mice confirmed no toxicity to the
heart/myocardium.
- These data are clearly aligned with the lack of
drug-related cardiotoxic events in Annamycin-treated patients
in ongoing clinical trials
- The role of topoisomerase II-beta in cardiotoxicity of
anthracyclines should be further investigated
- A video on the comparison of cardiotoxic effects of Annamycin
and doxorubicin on human cardiomyocytes can be accessed here
The Company also announced that the United States Patent and
Trademark Office (USPTO) formally issued U.S. Patent number
11,951,118 titled, "Preparation of Preliposomal Annamycin
Lyophilizate" (the '118 patent') to Moleculin and
The University of Texas System Board of Regents.
Annamycin is currently being evaluated in ongoing clinical
trials for the treatment of relapsed or refractory acute myeloid
leukemia (AML) and soft tissue sarcoma (STS) lung metastases. For
more information about the ongoing trials, please visit
clinicaltrialsregister.eu: EudraCT 2020-005493-10 or
clinicaltrials.gov: NCT05319587; and clinicaltrials.gov:
NCT04887298, respectively.
About Moleculin Biotech, Inc.
Moleculin Biotech, Inc. is a clinical stage pharmaceutical
company with a growing pipeline, including Phase 2 clinical
programs, for hard-to-treat tumors and viruses. The Company's lead
program, Annamycin is a next-generation anthracycline designed to
avoid multidrug resistance mechanisms with little to no
cardiotoxicity. Annamycin is currently in development for the
treatment of relapsed or refractory acute myeloid leukemia (AML)
and soft tissue sarcoma (STS) lung metastases.
Additionally, the Company is developing WP1066, an
Immune/Transcription Modulator capable of inhibiting p-STAT3 and
other oncogenic transcription factors while also stimulating a
natural immune response, targeting brain tumors, pancreatic and
other cancers, and WP1220, an analog to WP1066, for the topical
treatment of cutaneous T-cell lymphoma. Moleculin is also engaged
in the development of a portfolio of antimetabolites, including
WP1122 for the potential treatment of viruses, as well as cancer
indications including brain tumors, pancreatic and other
cancers.
For more information about the Company, please visit
www.moleculin.com and connect on Twitter, LinkedIn and
Facebook.
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 expected issuance of the
patent discussed above, the pace of enrollment in Moleculin's
clinical trials, the timing of Moleculin's ability to report
topline data from its studies, the timing of the commencement of
investigator-sponsored and/or externally funded clinical trials
which are outside the control of Moleculin, and whether the results
of Moleculin's preclinical animal models can be replicated in human
trials. 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 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.
Investor Contact:
JTC Team, LLC
Jenene Thomas
(833) 475-8247
MBRX@jtcir.com
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SOURCE Moleculin Biotech, Inc.