HOUSTON, Dec. 4, 2019 /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, today announced
additional positive interim safety and efficacy data from one of
the Company's two ongoing open label, single arm Phase 1/2 studies
of Annamycin for the treatment of relapsed or refractory acute
myeloid leukemia ("AML").
The Phase 1 portion of these clinical trials, which are
described in more detail later in this press release, is designed
to establish the safety of Annamycin and to determine the
Recommended Phase 2 Dose to be used in the Phase 2 portion of the
trials. While the Primary Endpoint of the Phase 1 portion is
safety, a Secondary Endpoint is the assessment of efficacy
generally defined as an improvement in bone marrow biopsy results
sufficient to qualify patients for a potentially curative bone
marrow transplant. The Company cautions not to place undue
reliance on interim results.
The third cohort in Poland
receiving a single dose of 180 mg/m2 in the Phase 1 dose
escalation portion of the trial was completed with no adverse
events and the trial will continue to the next cohort of 210
mg/m2. In the US trial, one patient has completed
treatment in the second cohort at 120 mg/m2. This
brings the total number of patients treated and evaluated at or
above 120 mg/m2 to 10. An additional patient in
the US has begun treatment at 120 mg/m2 but has yet to
complete post-treatment evaluation. The interim results for
these 10 patients are 1 CRi (defined as a complete response with
incomplete recovery of white blood cells and/or platelets) and 2
partial responses ("PRs" or where bone marrow blasts are reduced
50% and to below 25%). One additional patient was bridged to
bone marrow transplant ("BT") based on a sufficient reduction in
bone marrow blasts, bringing the total to 4 out of 10 patients at
or above 120 mg/m2 who have demonstrated efficacy.
In the latest cohort in Poland,
1 of the 3 patients treated at 180 mg/m2 had a PR
sufficient to qualify for a potentially curative bone marrow
transplant. The results for all 3 patients were reviewed by the
Safety Review Committee, which determined that no drug-related
adverse events were observed that would prevent advancing the trial
to the next higher dose level of 210 mg/m2. To
date in the European trial, only one adverse event related to
Annamycin has been reported; a patient experienced grade 2
mucositis (which resolved to grade 1 within 2 days). In the
Company's parallel US clinical trial, one new patient (the first of
cohort #2) achieved a "morphologically leukemia free state" or
MLFS, which also constitutes a CRi, after receiving a single dose
of 120 mg/m2.
We refer to Annamycin as a "next generation anthracycline,"
because it is designed to provide enhanced therapeutic benefits
when compared with traditional anthracyclines (like doxorubicin)
while reducing the potential for unwanted cardiotoxicity, or damage
to the heart. This design intent has previously been validated with
preclinical toxicology studies in animal models (as required by
FDA) demonstrating Annamycin has little to no cardiotoxicity when
compared with doxorubicin. Of the 14 patients treated thus far in
both trials, none has shown any evidence of cardiotoxicity.
This includes 7 patients in Poland
who were treated at levels above the US maximum allowable
cumulative anthracycline dose level (550 mg/m2), a
limitation not imposed on our trial in Europe. If upheld in further studies,
this lack of toxicity could be an important differentiator between
Annamycin and the currently approved anthracyclines, for which
cardiotoxicity is a well-known treatment limitation.
For example, a recent review published in Cardiovascular Drugs
and Therapy (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346598/)
reported that 65% of patients who received the equivalent of 550
mg/m2 of doxorubicin (a current standard of care
anthracycline) exhibited sub-clinical cardiotoxicity, defined as a
reduction in left ventricular ejection fraction >10% points to a
value <50%. Of the 5 patients mentioned above who were
treated in our European trial above 550 mg/m2, no
evidence of cardiotoxicity was detected. The same published
review also suggested that a better long-term indicator of
cardiotoxicity may be the measurement of an increase in a biomarker
called Troponin. When measured as an early biomarker of
cancer therapy-related cardiotoxicity, Troponin rise occurs
consistently in 21% - 40% of patients after treatment with current
standard of care anthracycline chemotherapy and, per the published
review, such an increase in Troponin is associated with an
increased risk of heart disease later in life. Of the 14
patients treated thus far in both of our Annamycin clinical trials,
none has shown an increase in Troponin levels.
"The interim data from our early-stage clinical trials of
Annamycin continues to meet or exceed our expectations, from both a
safety and efficacy perspective," commented Walter Klemp, Moleculin's Chairman and
CEO. "We believe the activity we are seeing – with 40% of
patients treated at or above 120 mg/m2 responding with
CRi's, PR's and/or bridging to a potentially curative bone marrow
transplant – is encouraging, especially since we have yet to reach
a maximum tolerable dose. Although the data is preliminary,
we are excited by the results to date, and to continue moving
forward. Importantly, recruitment continues to be much faster
in Europe than in the US. We
believe this is because Europe has
imposed fewer regulatory constraints on the level of anthracycline
dosing allowed and because there are far fewer competing AML
clinical trials in Poland, where
our clinical testing sites are located."
"We should also point out," Mr. Klemp continued, "that there are
two particularly important aspects of our development program that
distinguish the potential prospects for Annamycin. First, we
are studying the potential benefits of Annamycin in all AML
patients, not just a subset of the AML population based on a
particular gene mutation or other biomarker. Second,
Annamycin is being investigated not as an adjuvant to other
therapies, but as a single agent to treat relapsed or refractory
AML patients, primarily as a bridge to transplant. We also
believe the absence of cardiotoxicity, if it is borne out, would be
especially important for pediatric patients, in addition to
possibly suggesting Annamycin as an attractive alternative to
currently approved anthracyclines for treating cancers beyond
AML."
Dr. Robert Shepard, Moleculin's
Chief Medical Officer for Annamycin added: "Although it is still
early and the data are preliminary, I believe we may see that
Annamycin has significant activity against relapsed and refractory
AML. To have a 40% response rate this early in the
dose-escalating process is very encouraging. And if the
product ultimately is shown to have little or no cardiotoxicity –
as the preliminary data suggest – there is a real potential for
Annamycin to become the first approved anthracycline without a
dose-limiting cardiovascular risk. The use of anthracyclines
for induction therapy in acute leukemia is often, and
unfortunately, limited if such treatment would put them over what
is currently considered the 'lifetime maximum' anthracycline
exposure (or 'maximum cumulative dose'). However, authorities
in the EU took into account Annamycin's apparent lack of
cardiotoxicity and have allowed us to demonstrate this in patients
whose treatment would exceed this maximum cumulative dose. In
fact, 7 of the 9 patients treated to date in Europe substantially exceeded that lifetime
maximum based on their treatment with Annamycin and, of course,
have shown no cardiotoxicity."
Study Design
The Company is studying Annamycin in both the US and
Europe in open label, single arm
clinical trials to assess the safety and efficacy of Annamycin for
the treatment of adults with relapsed or refractory acute myeloid
leukemia. The US and European trials have the same study
design, consisting of a Phase 1 intended to establish a
"Recommended Phase 2 Dose" ("RP2D"), to which the studies will then
proceed. The Phase 1 studies provide for escalating doses in
cohorts of 3 patients each, with each successive cohort receiving
the next higher dose level until "dose limiting toxicities" prevent
further increases. Cohorts 1, 2 and 3 in Poland received a dose of 120, 150 and 180
mg/m2, respectively, and the results now permit moving
to 210 mg/m2. Cohort 1 in the US started at 100
mg/m2, and the results supported moving to 120
mg/m2, at which 1 patient has now been treated and
evaluated as having achieved a "morphologically leukemia free
state" or MLFS, which also constitutes a CRi. Because
one patient in US cohort 1 did not complete the evaluation
protocol, a fourth patient was added to complete that cohort.
Once the Company establishes an RP2D, the intent is for each
trial to advance to a Phase 2 arm planned to assess the safety and
efficacy of Annamycin in 21 additional patients.
The data reported here is preliminary as collected by
independent CRO site monitors per standard practice and is subject
to subsequent quality assurance review.
We have been and intend to continue reporting top-line results
by cohort in each trial, with each announcement also including an
update on the other trial. Top-line results will include
reporting of any drug-related adverse events ("AEs") and assessment
of cardiotoxicity, including ECHO or MUGA scans measuring change in
ejection fraction and measuring blood Troponin level, which is
considered a biomarker for potential long-term cardiovascular
impairment. To date, one patient experienced grade 2
mucositis (which resolved to grade 1 within 2 days) and no other
drug-related AEs have been reported. Also, no loss of
ejection fraction or rise in Troponin levels has been
reported. Top-line results will also include the number of
partial responses ("PRs"), complete responses ("CRs") and patients
deemed capable of progressing to a potentially curative bone marrow
transplant, which we term "bridge to transplant" ("BTs"), each of
which is essentially a function of the magnitude of reduction in a
patient's bone marrow blasts. For purposes of these clinical
trials, a CR means that the patient's bone marrow blasts reduced to
5% or less (with CRi meaning a CR where there was incomplete
recovery of white blood cell and/or platelet counts), a PR means
the patient's bone marrow blasts reduced by 50% and resulted in a
blast count of 25% or less, and a BT means patients are deemed
capable of progressing to a potentially curative bone marrow
transplant. To date, there has been 1 CRi in the US (@ 120
mg/m2), 2 PRs in Europe
(1 @ 120 mg/m2 and 1 @ 180 mg/m2) and 4 BTs
(1 in the US and 3 in Europe).
The US trial also differs from the European trial in that the
FDA would like to review safety data relating to cardiotoxicity
from patients treated prior to advancing beyond 120
mg/m2, as exceeding this dose level would require the
patient to exceed the established lifetime maximum exposure to
anthracyclines (presuming all anthracyclines are
cardiotoxic). To date, 100% of all 14 patients treated in
both the US and EU trials have shown no incidence of
cardiotoxicity, including 7 patients out of 9 treated in
Poland who exceeded the lifetime
maximum anthracycline exposure level. The Company believes
that the additional patient safety data gained from the European
trial may also assist in the FDA's review of Annamycin's cardiac
safety.
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. 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, targeting
brain tumors, pancreatic cancer and hematologic malignancies, and
WP1220, an analog to WP1066, 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.
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 the Company to
successfully recruit patients to complete its clinical trials, the
ability of Annamycin to show safety and efficacy in patients, and
the ability for Annamycin to be an alternative to currently
approved anthracyclines for treating cancers other than AML.
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. The
Company cautions investors not to place undue reliance on the
interim results announced today.
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SOURCE Moleculin Biotech, Inc.