– Preliminary Phase 1b data demonstrated clinical activity, defined
as stable disease or better
– Company determines RP2D to be 360
mg/m2 and will begin Phase 2 recruitment
– Annamycin has Fast Track Status and Orphan
Drug Designation from FDA for the treatment of soft tissue
sarcoma
HOUSTON, July 28,
2022 /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 it
has completed the safety review of the fourth cohort in a dose
escalation clinical trial evaluating Annamycin for the
treatment of soft tissue sarcoma (STS) lung metastases, thus
concluding the Phase 1b portion of
its U.S. Phase 1b/2 clinical trial. Preliminary results from
the study continue to document clinical activity for Annamycin in
the treatment of STS. The safety review committee (SRC) has deemed
the dose of 390 mg/m2 to be safe after conclusion of the
fourth cohort. Notwithstanding that there was safety at this dose
level, tolerability issues present at the 390 mg/m2 dose
level caused delays in follow-on cycles and the reduction of
subsequent doses, suggesting that a Recommended Phase 2 Dose (RP2D)
below 390 mg/m2 was warranted.
With this in mind and with the recommendation of the SRC, the
Company has determined that the RP2D will be 360 mg/m2
for the first three subjects in the Phase 2 portion of the study.
The SRC will then review the clinical safety data at this dose and
determine whether the RP2D should be further reduced to 330
mg/m2 prior to proceeding with the additional 22
subjects. In addition to continuing to assess safety, including
gathering additional information about short-term side effects and
possible risks, this Phase 2 portion of the study will also explore
the efficacy of Annamycin as a single agent for the treatment of
subjects with STS lung metastases for whom prior chemotherapy has
failed, and for whom new chemotherapy is considered
appropriate.
In the Phase 1b portion of the
study, 15 subjects were enrolled and treated per the protocol in
four cohorts to determine the maximum tolerable dose and/or the
RP2D. Each cohort had three subjects, except for the fourth
cohort, which (per the protocol) was expanded to six subjects after
a dose-limiting toxicity (DLT) occurred in a single subject. The
Company concluded the Phase 1b
portion after the fourth cohort of 390 mg/m2 was
documented to be safe. Up to 28 subjects, to account for potential
over enrollment, will be enrolled at the RP2D in Phase 2 to focus
more on quantifying efficacy as well as providing additional safety
information.
"As we end the Phase 1b portion of
this trial, the preliminary data continue to be encouraging," said
Moleculin Chairman and CEO Walter
Klemp. "Of the fifteen subjects treated per the protocol,
two continue with treatment, and eight subjects have been followed
without evidence of disease progression for two months or greater,
with three of the eight free of disease progression for 120 days or
more. These data are early-stage, and we look forward to developing
confirmatory data from future studies. However, based on the data
available thus far, we believe Annamycin has the potential to bring
a new and effective treatment option to patients with significant
unmet needs."
Mr. Klemp added, "We're also encouraged by the pace of
recruitment to date for this trial. To have completed the Phase
1b in just over one year was faster
than we expected, especially for a rare disease like STS lung
metastases. This is encouraging as we open the Phase 2 portion of
the study."
The summary of interim Phase 1b
data, which are preliminary and subject to change, from the four
cohorts of the study are as follows:
First Cohort (210 mg/m2):
- Two subjects received 6 cycles of Annamycin, initially having
stable disease, and were then discontinued due to progressive
disease.
- One subject received 1 cycle, but then discontinued from the
study because of a Dosing Delay greater than the time between doses
permitted by the protocol. At the End of Study scan performed
39 days post initiation of treatment, the subject had stable
disease. The subject was followed and continued to exhibit disease
free progression up to 61 days after treatment, at which point the
subject began a different therapy.
Second Cohort (270 mg/m2):
- In one subject, the end of cycle 2 scan showed a partial
response (≥30% reduction in tumor size), and when scanned at the
end of cycle 4 the subject showed stable disease. The subject
subsequently discontinued from the study, electing to undergo
surgical resection to potentially eradicate the disease. The
subject is continuing to be followed and at the last follow-up no
disease progression was reported at 272 days.
- One subject was discontinued from the study when the end of
cycle 2 scan revealed progressive disease.
- One subject received 1 cycle of treatment and discontinued
treatment due to a Dosing Delay. The End of Study scan revealed
progressive disease.
Third Cohort (330 mg/m2):
- One subject received 1 cycle and was discontinued when an
interim, unscheduled scan revealed progressive disease.
- One subject was discontinued from the study when the end of
cycle 2 scan revealed progressive disease.
- One subject was treated with 2 cycles and the end of cycle 2
scan revealed stable disease. The subjected elected to
withdraw from receiving any further treatment. The subject was
followed and no disease progression was reported at 146 days. The
subject elected at that time to discontinue from further follow-up
in the study.
Fourth Cohort (390 mg/m2):
Efficacy data
for this cohort are incomplete as not all subjects have received
their scans and treatment is ongoing.
- One subject received 3 cycles of treatment without evidence of
any DLTs, with the last 2 cycles at a reduced dose of 292
mg/m2 due to a drug tolerability issue that did not
qualify as a DLT. The subject exhibited stable disease at the end
of cycle 2. The subject showed progressive disease in the end of
treatment scan on the 78th day.
- One subject was discontinued from the study after 2 cycles with
cycle 2 administered at a reduced dose of 292 mg/m2. The
subject discontinued receiving cycles because of a DLT of febrile
neutropenia, and the cohort was expanded per the protocol. The end
of cycle 2 scan revealed stable disease. The subject initiated
additional therapy unrelated to the study on the 68th
day and will continue to be followed for Overall Survival.
- One subject received 3 cycles of treatment without evidence of
any DLTs, with the last 2 cycles administered at reduced doses, due
to drug tolerability. The subject exhibited stable disease at the
end of cycle 2. The subject showed progressive disease in an
unscheduled scan on the 79th day.
- One subject received 4 cycles without evidence of any DLTs,
with the last three cycles administered at a reduced dose of 292
mg/m2, due to drug tolerability. The end of cycle 4
scans revealed stable disease. The subject is ongoing in the
study.
- One subject received 3 cycles without evidence of any DLTs,
with the last two cycles administered at a reduced dose of 292
mg/m2, due to drug tolerability. The end of cycle 2
scans revealed stable disease. The subject is ongoing in the
study.
- One subject received 1 cycle without evidence of any
dose-limiting toxicities and is ongoing in the study.
- One subject received a markedly lower dose than the specified
390 mg/m2 in a protocol violation by the site, also
without evidence of any DLTs. That subject's safety data, but not
efficacy, is deemed to be evaluable in the study.
"Consistent with our earlier and ongoing acute myeloid leukemia
trials, in the subjects evaluated to date we have seen a complete
absence of cardiotoxicity in our trials," Mr. Klemp said. "Again,
these are early-stage data, but we're seeing consistent results in
this regard across our Annamycin studies, and we think they're
important because, even though anthracyclines are considered a
cornerstone chemotherapy for many types of cancer including STS
lung metastases, all currently approved anthracyclines are
significantly cardiotoxic. Annamycin was designed to overcome this
problem and we believe it has the potential to become the first
non-cardiotoxic anthracycline approved for use. If these data
continue and our product is approved, Annamycin may not only reduce
the risk of many current anthracycline treatment regimens, but it
could also enable longer treatment periods with reduced concern for
cardiac risk."
Annamycin currently has Fast Track Status and Orphan Drug
Designation from the U.S. Food and Drug Administration for the
treatment of soft tissue sarcoma, in addition to Orphan Drug
Designation for the treatment of relapsed or refractory acute
myeloid leukemia. For more information about the Phase 1b/2
study evaluating Annamycin for the treatment of STS lung
metastases, please visit clinicaltrials.gov and reference
identifier NCT04887298.
Study Design
In Phase 1b, Annamycin was
administered as an intravenous (IV) infusion over 2 hours on Day 1,
followed by 20 days off (1 cycle = 21 days). Subjects visit the
study site every 21 days (±3 days) at which time safety monitoring
– including for adverse events (AEs), as well as a physical
examination, laboratory evaluations (clinical chemistry, complete
blood count), vital signs, weight measurements, Eastern Cooperative
Oncology Group (ECOG) performance status, and electrocardiograms
(ECGs) – is performed, followed by an IV infusion of study drug.
Cardiac function is followed by echocardiogram (ECHO) scans at
screening, at the end of the first two cycles and then following
every other cycle thereafter, at the End of Treatment visit, and if
feasible, during follow up at 6 months (±1 month) and 1 year (±1
month) after study drug discontinuation. As long as the
Investigator considers that the benefits of treatment with
Annamycin continue to outweigh the risks, treatment will continue
every 21 days until tumor progression is observed or unacceptable
toxicity occurs.
Tumor response is monitored every 6 weeks (±1 week) from Cycle 1
Day 1 during treatment, at the End of Treatment visit, and then
every 3 months (±1 month) until disease progression using RECIST
1.1 criteria. Those subjects who leave the study after a maximum
response is achieved and who do not start another therapy will be
followed every 3 months (±1 month) for progression-free survival
(PFS). If a subject receives further therapy after discontinuing
from the study, they will be followed only for overall survival
(OS) and if feasible, follow-up ECHO scans at 6 months (±1 month)
and 1 year (±1 month) will be conducted after study drug
discontinuation.
About Annamycin
Annamycin is the Company's
next-generation anthracycline that has been shown in animal models
to accumulate in the lungs at up to 30-fold the level of
doxorubicin. Importantly, Annamycin has also demonstrated a lack of
cardiotoxicity in multiple early-stage human clinical trials,
including ongoing trials for the treatment of acute myeloid
leukemia (AML) and STS lung metastases. For that reason, although
additional data will be necessary, the Company believes Annamycin
may not face the same usage limitations imposed on doxorubicin, one
of the most common currently approved anthracyclines. Annamycin is
currently in development for the treatment of AML and STS lung
metastases and the Company believes the drug may have the potential
to treat additional indications.
About Moleculin Biotech, Inc.
Moleculin Biotech,
Inc. is a clinical stage pharmaceutical company focused on the
development of a broad portfolio of drug candidates for the
treatment of highly resistant 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 COVID-19 and other 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 final determination of the RP2D,
the ability of Annamycin to demonstrate safety and efficacy in
subjects, and the ability of the STS lung metastases clinical trial
to continue the recruitment of subjects and the ability of
Annamycin to eventually be approved by the FDA. 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.