–
MB-106: CR rate of 38% (N=8) with durability up to 8
months
–
Builds on CRi rate of 60% in MB-105 monotherapy AML trial last
cohort (N=5)
–
MB-107: Phase 1B median extended
overall survival of 11 months for heavily pre-treated subjects
(N=15)
–
MB-107 Phase 1B/2 median
progression free survival (PFS) of 3.4 months for subjects dosed at
or below 330 mg/m2 and less than 3 prior therapies
(N=9)
–
100% of Annamycin subjects in multiple studies (N=66) continue
to show no signs of cardiotoxicity during study
HOUSTON, Nov. 13,
2023 /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 provided a
preliminary update on recent clinical activity and expected near
term milestones across its clinical development pipeline in its
quarterly filing with the Securities and Exchange Commission.
"Despite a host of recent new drug approvals, the most important
therapeutic tool for treating AML and advanced STS continues to be
an anthracycline. We believe the data we are now showing in
Annamycin's clinical trials on those indications are demonstrating
a potential to finally bring an anthracycline to the table for
those patients who have until now been prevented from using them,"
Walter Klemp, Chairman and Chief
Executive Officer of Moleculin stated. "Importantly, as we continue
to show zero cardiotoxicity in 100% of subjects in multiple
studies, Annamycin is now also showing substantial activity in
Phase 2 studies across two indications."
"Having 38% of subjects with a median age of 68 in our MB-106
AML study receiving a full course of Annamycin show a complete
response with durability of up to approximately 8 months and
counting, we believe, is exceptional while also demonstrating no
cardiotoxicity," Dr. Paul Waymack,
Senior Chief Medical Officer said. "Adding to this, we are showing
in our Phase 1B/2 study with
Annamycin treating soft tissue sarcoma (STS) with pulmonary
metastases for subjects with no limit on prior therapies (median of
3; range of 1-11) PFS of 2.2 months or better for 59% of the
subjects (N=32). In subjects with fewer prior therapies (prior
therapies <2) and dosed with Annamycin at or below 330
mg/m2, this increased to 78% and, additionally, we are
showing PFS of 3.4 months for 56% (N=9) of these subjects. Having a
preliminary median of 11.3 months of overall survival once the
subject has entered into our Phase 1B
study (Extended OS), is exciting as these subjects were heavily
pre-treated. For the overall study, we have an opportunity for the
Extended OS and PFS data to get better as subjects continue to be
monitored."
Ongoing Clinical Trial Updates
Next Generation Anthracycline – Annamycin
Annamycin is the Company's next-generation anthracycline that
has been designed to be non-cardiotoxic (unlike currently
prescribed anthracyclines) and has been shown in animal models to
accumulate in the lungs at up to 30-fold the level of doxorubicin
(a commonly prescribed anthracycline and the standard of care
chemotherapy for advanced STS), as well as demonstrating the
ability to avoid the multidrug resistance mechanisms that typically
limit the efficacy of doxorubicin and other currently prescribed
anthracyclines. An independent expert evaluated the first 62
subjects in the Company's four clinical trials and confirmed that
there are no signs of cardiotoxicity. In total 66 subjects (4 are
yet to be reviewed) have been treated in the Company's clinical
trials and none have shown any signs of cardiotoxicity. This
includes 50 subjects treated over the lifetime maximum
anthracycline dose set by the U.S. Food and Drug Administration
(FDA). Annamycin is currently in development for the treatment of
both first line therapy and therapy for relapsed or refractory
acute myeloid leukemia (AML), as well as, STS lung metastases (STS
lung mets), and the Company believes the drug may have the
potential to treat additional indications.
AML
The Company is currently conducting its Phase 1B/2 clinical trial evaluating Annamycin in
combination with Cytarabine (also known as "Ara-C" and for which
the combination of Annamycin and Ara-C is referred to as AnnAraC)
for the treatment of subjects with AML as both first line therapy
and for subjects who are refractory to or relapsed after induction
therapy (MB-106). clinicaltrialsregister.eu: EudraCT 2020-005493-10
or clinicaltrials.gov: NCT05319587. The Company has not treated any
first line subjects to date.
Table 1
– Summary of Annamycin Responses in AML Studies
|
Study
|
Study MB-105
Monotherapy – Last
Cohort at 240
mg/m2 (RP2D)
|
Study MB-106
Combination Therapy –
Phase 1B
(Annamycin at 190-
230 mg/m2)
|
Study MB-106
Combination Therapy
– Phase 2 To Date
(Annamycin at 230
mg/m2)
|
Study MB-106
Combination Therapy
– Phase 1B/2 To Date
(Annamycin at 190-
230 mg/m2)
|
Therapy
|
Annamycin
– Single
Agent
|
Ara-C + Annamycin
"5+3+
|
Ara-C + Annamycin
"5+3+
|
Ara-C + Annamycin
"5+3+
|
Subjects To
date
|
5
|
6
|
2
|
8
|
CRs
|
0
|
2
|
1
|
3
|
CRis
|
3
|
0
|
0
|
0
|
Total Response(s)
or
CRcs
|
3
|
2
|
1
|
3
|
Overall Response
(CRc) Rate
|
60 %
|
33 %
|
50 %
|
38 %
|
Median Prior
Therapies (Months of
Prior Therapy))
|
6 (N/A)
|
2.5 (9)
|
3 (6)
|
3 (9)
|
Median Age - Years
(Range)
|
65 (62-73)
|
66 (32-78)
|
69 (69-70)
|
68 (32-78)
|
Durability of
CRs
|
Not followed
|
Approximately 8 and
3
months, respectively,
to date for the 2 CRs
|
Not Available at
This
Time
|
See Data to
Left
|
N/A (Not
available)
|
For all subjects
receiving a full course of Annamycin
|
Above is a table that shows a summary of the data to date for
MB-106 and, for reference, the data for the last cohort in the
MB-105 AML study with Annamycin as a monotherapy is shown as well.
The data described and shown above is preliminary and subject to
change, except for the MB-105 data where a Clinical Study Report
has been completed.
MB-106 Phase 1B/2 clinical trial
began dosing subjects in March 2023.
Nine clinical sites in Poland and
Italy have been activated for the
MB-106 trial. The Company is planning for a total of up to [eleven]
sites in the European Union (EU).
The median number of prior therapies for these 3 subjects in the
first cohort was five (range of one to ten). One subject, who was
78 years of age at the time of the study initiation and enrolled
after a single prior multi-year therapy, achieved a CR that
has continued to be durable at approximately 8 months. This subject
has received a second course of treatment at the direction of the
treating physician and as allowed per the protocol. The other 2
subjects were shown to have disease progression. On August 7, 2023, Moleculin successfully completed
the second cohort at 230 mg/m2 of Annamycin in this
combination study. Four subjects were treated in this cohort, 1 is
believed to be relapsed from one or more prior therapies and 3 are
believed to be refractory from up to three prior therapies. One
subject was replaced due to a Serious Adverse Event (SAE)
experienced on Day 1 of dosing. The SAE was determined to be
unrelated to Annamycin and definitively related to Cytarabine. The
Company, at the recommendation of the safety review committee,
deemed the second cohort dose as safe and opened recruitment,
including for both first line therapy and for subjects who are
refractory to or relapsed after induction therapy, to the Phase 2
portion of the trial. The median number of prior therapies for the
3 evaluable subjects in the second cohort was two (range of one to
three) and the median age was 67. One subject, who was 64 years of
age at the time of enrollment into the study with one prior
therapy, was preliminarily recorded as a CR with an incomplete
recovery of the bone marrow, or CRi, per the protocol. This has
since been deemed a CR, which has shown to be durable for
approximately three months, which has allowed this subject to
proceed to a bone marrow transplant. The other 2 subjects were
shown to have disease progression. Durability of CR's is confirmed
by and repeat bone marrow aspirates (BMA's).
The total CRs in the Phase 1B
portion of this combination trial represent 33% (n=6). Notably,
these CRs are considered durable. The median age of these subjects
was 66.
On October 2, 2023, Moleculin
announced the initial subjects had been treated in the Phase 2
portion of MB-106. The data above is as reported by the
investigation sites as of November 9,
2023.
The Company has recruited, treated, and evaluated 3 subjects in
the Phase 2 portion of the trial. One subject has been evaluated
and determined to be a [CR]. The Company will assess the durability
in the near future. Another subject in the Phase 2 portion died
from a stroke (deemed not be related to Annamycin) prior to being
re-biopsied to determine disease status. The third has undergone a
re-biopsy which shows zero blasts in the marrow and that data is
now being assessed by the investigator. This latest subject is not
included in the chart above. The median age of the first two
subjects is 69 years (range of 69 to 70) and the median number of
prior therapies for these subjects is three (both are three). Other
subjects in the Phase 2 portion of the trial are in the process of
screening and treatment. The Company intends to treat up to
21 subjects in this Phase 2 portion of the trial. The Company may
recruit an additional 3 subjects depending on recruitment. At the
Company's rate of recruitment plus the addition of another three
sites for the trial, Moleculin expects to complete recruitment by
early 2024.
The total CRs in both Phases to date in MB-106 represent 38%
(n=8), and although sufficient time has not passed to assess
durability for the latest of these CRs, the 2 earlier CRs have now
shown durability. The median baseline bone marrow assessments
for the 3 CRs was 74.2 (range of 20 to 80).
STS Lung Mets
Table
2
|
MB-107 Summary as of
November 9, 2023
|
|
|
|
Progression
Free
Survival
Months (mos)
|
All
Subjects
|
Phase 1B
All
Subjects
|
Phase 2
All
Subjects
|
All Subjects
Treated at
<
330
mg/m2
|
All Subjects
with 2 or
Fewer
Prior
Therapies
(< 2PT)
|
All Subjects
<
330
mg/m2 &
< 2PT
|
1 mos or
>
|
100 %
|
100 %
|
100 %
|
100 %
|
100 %
|
100 %
|
2 mos or
>
|
59 %
|
67 %
|
53 %
|
61 %
|
83 %
|
78 %
|
3 mos or
>
|
25 %
|
27 %
|
24 %
|
30 %
|
42 %
|
56 %
|
4 mos or
>
|
16 %
|
13 %
|
18 %
|
22 %
|
25 %
|
33 %
|
5 mos or
>
|
9 %
|
7 %
|
12 %
|
13 %
|
8 %
|
11 %
|
6 mos or
>
|
6 %
|
0 %
|
12 %
|
9 %
|
8 %
|
11 %
|
n =
|
32
|
15
|
17
|
17
|
12
|
9
|
Median mos
|
2.2
|
2.6
|
2.0
|
2.1
|
2.7
|
3.4
|
Median Prior
Therapies
(Range)
|
3 (1-11)
|
3 (1-9)
|
3 (1-11)
|
3 (1-11)
|
2 (1-2)
|
2 (1-2)
|
|
|
|
|
|
|
|
Median O/S
mos
|
N/A
|
11.3
|
N/A
|
N/A
|
N/A
|
N/A
|
Overall survival (OS);
Not available for Phase 2 subjects at this time, as majority of
subjects continue survival (N/A)
|
On September 21, 2023, Moleculin
announced the completion of enrollment in the Phase 2 portion of
its U.S. Phase 1B/2 clinical trial
evaluating Annamycin as monotherapy for the treatment of soft
tissue sarcoma lung metastases (MB-107). Subjects who had stable
disease at the time of study discontinuation will continue to be
followed for progression free response and overall survival. All
subjects had pulmonary metastasis from soft tissue sarcoma and at
least one prior therapy. There was no limit on how many prior
therapies a subject could have prior to entering this study. Most
subjects were heavily treated with other therapies prior to
entering our trial with our treatment representing the fourth
median therapy for all subjects in the Phase 1B and Phase 2 portion of the trial (range of two
to twelve). As of November 6, 2023 as
reported by the investigation sites, most subjects in Phase 2 are
alive so overall survival data is not available at this time. Above
in Table 2 is a summary of progression free survival for evaluable
subjects, as discussed further below, by groupings and median
overall survival for all subjects evaluable in Phase 1B.
In the Phase 1B portion of the
trial, subjects were treated from 210 mg/m2 to 390
mg/m2. In the Phase 2 portion of the trial, an
exploratory RP2D of 360 mg/m2 was initiated for the
first 3 subjects and a final RP2D of 330 mg/m2 was
determined and 14 subjects were treated.
Including the 3 subjects treated at the same dose in the Phase
1B portion of this trial, this
equates to 17 total subjects measurable for efficacy at the 330
mg/m2 dose level. Including all measurable subjects at
all dose levels in the Phase 1B
portion of the trial, 32 subjects were treated with at least one
cycle in this study and 27 received at least two cycles of
treatment. For these subjects, the median time to entering the
MB-107 trial from the time of initial diagnosis is estimated to be
approximately 20 months, and these subjects have been mostly
heavily treated previously for STS lung mets prior to entering the
Company's study.
Once all data is collected, Moleculin plans to release a more
in-depth presentation of the topline data for this study in 2024.
The above information in Table 2 was shared with the Company's
investigators in a meeting held during the Connective Tissue
Oncology Society Annual Meeting (CTOS) in Dublin, Ireland in early November 2023. Based on the data as shown in
Table 2 above, Moleculin believes the following observations are in
order:
- Very few trials for subjects with such advanced (median = 20
months from initial diagnosis; all with lung metastases in MB-107)
disease progression have been published, making comparisons to
historical performance difficult.
- With this in mind, median OS for subjects in the Phase
1B portion of this study is currently
at 11 months, which the Company believes is notable.
- Overall median Progression Free Survival (PFS) for the trial is
2.2 months (range 1.2 to 6.9 months) with 7 subjects discontinuing
early due to thrombocytopenia. Five of these subjects negatively
impacted this median PFS, which the Company believes was
exacerbated by the extreme advanced stage of the patients and their
being weakened by prior therapies.
- Median PFS improved to 3.4 months for lower doses of Annamycin
(≤330 mg/m2) versus the maximum dose used in the trial and for
subjects who had fewer prior therapies (<2).
- These data suggest to us that Annamycin may be best positioned
as a first line alternative to the current standard of care with an
anthracycline and where the combination of high patient response
rate, significant improvement in OS and the absence of
cardiotoxicity may improve patient outcomes.
All data presented above from the MB-107 trial are preliminary
and subject to change.
Expected Upcoming Annamycin Milestones
- AML
- In-depth data review and presentation of topline data on MB-106
clinical trial.
- MB-106 End of Phase 2 (EOP2) Meeting.
- Identify next phase of development / pivotal program.
- Initiate pivotal program.
- STS Lung Mets
- Final MB-107 data readout.
- Identify next phase of development / pivotal program.
- Initiate first line study STS.
Flagship Immune/Transcription Modulator – WP1066
Moleculin is in ongoing discussions with multiple academic
institutions in separate programs evaluating WP1066 for the
treatment of glioblastomas and/or pediatric brain tumors. The
Company expects to finalize agreements with Northwestern University and FDA filings in the
early 2024 (Clinicaltrials.gov ID: NCT05879250).
Recent Activity Highlights
- Ongoing progress in development of an intravenous formula for
WP1066.
- The Company supplied drug product to an externally funded
pediatric brain tumor trial with WP1066 up to its conclusion in
February 2023 and expects additional
externally funded clinically trials for WP1066 (in combination with
radiation) in 2023 in the U.S. and, possibly, in Southeast Asia.
Expected Upcoming Milestones
- Report topline results from investigator-initiated Phase 1
study in pediatric brain tumors.
- Seek external funding opportunities for an
investigator-initiated clinical trial in adult and pediatric cancer
patients in 2023.
- Announce progress regarding an IV formulation by the end of
2023 or in early 2024.
Metabolism/Glycosylation Inhibitor – WP1122
Portfolio
WP1122 was developed as a prodrug of 2 deoxy-D-Glucose (2-DG) to
provide a more favorable pharmacological profile and was found to
have greater potency than 2-DG monotherapy in preclinical models
where tumor cells require higher glycolytic activity than normal
cells. WP1122 has also been shown to have a greater antiviral
effect than 2-DG against SARS-CoV-2 in MRC-5 cells in culture. The
improved pharmacokinetic and pharmacodynamic (PK/PD) profile of
WP1122 compared to 2-DG was noted in mice following oral dosing at
equimolar (i.e., equivalent levels of 2-DG) doses. The WP1122
Portfolio includes numerous analogs, including WP1096, which has
demonstrated the potential for broad antiviral capabilities in a
wide range of in vitro models including multiple
arenaviruses, filoviruses, Zika virus, and HIV. The Company looks
forward to the potential of additional externally funded research
to confirm such activity.
Expected Upcoming Milestones
- Report preliminary findings of National Institutes of Health
(NIH) funded animal testing of WP1096 in the Tacaribe
Arenavirus.
- Identify investigators interested in initiating a clinical
trial to study the safety, pharmacokinetics and efficacy of oral
WP1122 in adult patients with GBM.
General Information on the Company's Core
Technologies
Annamycin currently has Fast Track Status (FTS) and Orphan Drug
Designation (ODD) from the FDA for the treatment of soft tissue
sarcoma, in addition to ODD for the treatment of acute myeloid
leukemia. WP1066 has ODD for the treatment of GBM and has four
indications designated for the FDA Rare Pediatric Disease Priority
Review Voucher (PRV) Program. WP1122 has ODD and FTS for GBM, as
well. For more information about the Company's trials, please
visit clinicaltrials.gov.
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 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 Expected Upcoming
Milestones set forth 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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