- Preeclampsia Program to be Initiated with a Phase 2
Investigator-sponsored Trial Beginning in Q4 2024
- Key Proof-of-Concept Results Expected in the First Half of
2025
- Management will Host a Conference Call Thursday, June 27,
2024 at 8:00 AM Eastern Time / 7:00 AM Central Time to Discuss
Preeclampsia
- Company to Host Preeclampsia Key Opinion Leader Event July
29, 2024
DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage
biopharmaceutical company focused on developing novel treatments
for severe ischemic diseases, today announced that it plans to
expand its DM199 (rinvecalinase alfa; recombinant human tissue
kallikrein-1 (rhKLK1)) clinical development program into
preeclampsia. Preeclampsia is a life-threatening
pregnancy-associated vascular disorder characterized by new onset
hypertension with proteinuria, and/or end organ dysfunction, and
poses significant risks to both mother and baby. There are no
approved therapeutics for preeclampsia in the U.S. or Europe.
“Multiple lines of evidence demonstrate that DM199 can lower
blood pressure, and unlike contra-indicated small molecule
anti-hypertensives, DM199 is a large molecule protein that has been
shown to not cross the placental barrier in animals, potentially
creating a significant safety advantage in pregnancy disorders,”
commented Rick Pauls, DiaMedica’s President and Chief Executive
Officer. He added, “The planned trial is highly capital efficient,
enrolling up to 120 participants for an estimated cost of
approximately $1.5 million, and has the potential to provide robust
proof of concept.”
DM199 for Preeclampsia: Scientific Rationale and
Clinical/Preclinical Support
DM199 has the potential to lower blood pressure, enhance
endothelial health, and improve perfusion to maternal organs and
the placenta. This mode of action is believed to occur through the
increased production of endothelial nitric oxide, prostacyclin, and
endothelial-derived hyperpolarizing factors (EDHFs). These pathways
are typically depressed or impaired in preeclampsia. DM199 holds
the potential to be disease modifying for preeclampsia patients if
it can effectively increase placental perfusion and reduce
placental hypoxia, a significant contributor to the pathophysiology
of preeclampsia.
DM199 has demonstrated blood pressure reductions in multiple
prior studies. New results from analysis of overall participants
with elevated blood pressure (baseline systolic blood pressure ≥
130 mmHG) from the DM199 Phase 2 REDUX clinical trial in three
types of chronic kidney disease (CKD) which demonstrated a
statistically significant reduction in systolic blood pressure
(SBP) at day 95:
REDUX Phase 2 CKD Trial
Results: Baseline SBP*
SBP ≥130 mmHg
SBP ≥140 mmHg
SBP ≥150 mmHg
Day 95 Change from Baseline
-7.7 mmHg
-12.6 mmHg
-22.1 mmHg
P-value (Student’s T-Test)
0.011
0.004
0.003
Number of Participants
47
31
15
*Includes participants from all
cohorts
DiaMedica has also completed studies on fertility, embryofetal
development and pre- and post-natal development in animal models,
which support the potential safety in pregnant humans. DiaMedica
recently completed a placental transfer study in pregnant rats in
which DM199 did not cross the placental barrier. Specifically,
DM199 was detectable in the maternal blood, but undetectable in the
fetal blood.
“With scientific evidence that KLK1 is key to endothelial
health, I am optimistic about the potential of DM199 to reverse
disease severity in addition to improving blood pressure control,”
commented Professor Stephen Tong, MD, PhD, Obstetrics and
Gynaecology and Professor at Mercy Hospital for Women and
Co-Director of Mercy Perinatal at The University of Melbourne. He
further commented, “if DM199 can also open up maternal blood
vessels to improve blood flow to the placenta, it may serve as a
disease-modifying therapy for preeclampsia. Additionally, it could
address fetal growth restriction, a separate yet related pregnancy
disorder that is more prevalent and currently has no FDA-approved
therapeutics.”
The Phase 2 Investigator-Sponsored Trial in Preeclampsia and
Fetal Growth Restriction
Up to 90 women with preeclampsia, and potentially 30 subjects
with fetal growth restriction, will be evaluated with the first
subject anticipated to be enrolled in the fourth quarter of 2024,
pending regulatory approval. Part 1A topline study results are
anticipated in the first half of 2025, which will demonstrate
whether DM199 is safe, lowers blood pressure, and dilates
intrauterine arteries to increase placental blood flow.
This Phase 2 open-label, single center, single-arm, safety and
pharmacodynamic, proof-of-concept, investigator-sponsored study of
DM199 in treating preeclampsia will be conducted at the Tygerberg
Hospital, Cape Town, South Africa (SA), under the direction of
Catherine Cluver, MD, PhD, Professor of Maternal/Fetal Medicine,
Stellenbosch University, Stellenbosch, SA, in collaboration with
DiaMedica. “Women suffering from preeclampsia have few therapeutic
options. Controlling hypertension and reducing organ damage and
premature delivery is a key goal. DM199 holds promise as a novel
medication and we look forward towards evaluating its potential
benefits in managing patients with preeclampsia,” said Professor
Cluver.
The planned Phase 2 trial of DM199 for preeclampsia will be
conducted in up to three parts as follows:
Participants
Summary
Part 1
Up to 60
Pregnant woman with preeclampsia
between 27 to 42 weeks of gestation and are scheduled to deliver
within 72 hours, SBP ≥150 mmHg. Part 1A involves an ascending
dose-finding study recruiting up to 30 participants. Part 1B is an
expansion cohort of an additional 30 participants at the dose
established in Part 1A. Key data from Part 1 will be used to assess
safety and tolerability, and to assess whether DM199 acutely lowers
blood pressure, acutely dilates intrauterine arteries (measured
with Doppler ultrasound), and whether it crosses the placental
barrier (measured in cord blood), as well as other disease specific
measurements and biomarkers.
Part 2
Up to 30
Pregnant woman with preeclampsia
between 27 to 33 weeks gestation in the expectant management
setting, aimed at safely prolonging the pregnancy. Key data from
Part 2 is expected to include assessments of safety and
tolerability, the number of days pregnancy is prolonged, changes in
the urinary albumin-to-creatinine ratio over seven days compared to
baseline, need to increase or decrease other antihypertensive
agents, as well as other disease-specific measurements and
biomarkers.
Part 3
Up to 30
Pregnant woman between 26 to 32
weeks of gestation with fetal growth restriction (FGR) but without
preeclampsia, contingent upon observing if DM199 can enhance
intrauterine blood flow as assessed by Doppler ultrasound
evaluation in Part 1. Key data from Part 3 is expected to include
changes in uterine artery and ophthalmic arterial blood flow
(measured by Doppler ultrasound), birthweight centile and fetal
growth trajectory.
The investigators on the study include Catherine Cluver, MD,
PhD, Professor of Maternal/Fetal Medicine, Stellenbosch University,
Stellenbosch, South Africa, Stephen Tong, MD, PhD, Professor at
Mercy Hospital for Women and Co-Director of Mercy Perinatal at The
University of Melbourne, and Sue Walker, MD, PhD, Head of the
Department of Obstetrics and Gynecology, University of Melbourne,
and Director of Perinatal Medicine at Mercy Hospital for Women.
“Gaining access to these leading academics and trailings in the
field of preeclampsia is invaluable and underscores the potential
of DM199 for treating this grave condition. Additionally, as this
is an investigator-sponsored trial, it will not significantly
consume DiaMedica’s clinical resources, allowing us to maintain
focus on the Remedy AI clinical trial,” commented Lorain Mazurka,
MD, DiaMedica’s Chief Medical Officer. “The United States has the
highest rate of maternal mortality among high-income nations, and
according to the U.S. Centers for Disease Control and Prevention,
black women are three times more likely to die during pregnancy
than white women. If DM199 can address this unmet need, it would be
a significant benefit for these women and their babies.”
More details on DM199 for preeclampsia and fetal growth
restriction will be presented at a key opinion leader event to be
held on July 29, 2024. Instructions for participating in this event
will be provided in the coming weeks.
Conference Call and Webcast Information
DiaMedica Management will host a conference call and webcast to
discuss its clinical expansion into preeclampsia on Thursday, June
27, 2024, at 8:00 AM Eastern Time / 7:00 AM Central Time:
Date:
Thursday, June 27, 2024
Time:
8:00 AM ET / 7:00 AM CT
Web access:
https://app.webinar.net/3J46BqeBGXV
Dial In:
(646) 357-8785
Conference ID:
53747
Interested parties may access the conference call by dialing in
or listening to the simultaneous webcast. Listeners should log on
to the website or dial in 15 minutes prior to the call. The webcast
will remain available for playback on the Company’s website, under
investor relations - events and presentations, following the
earnings call and for 12 months thereafter. A telephonic replay of
the conference call will be available until July 4, 2024, by
dialing (888) 660-6345 (US Toll Free) and entering the replay pass
code: 53747#.
About Preeclampsia
Preeclampsia is a serious pregnancy disorder that typically
develops after the 20th week of gestation, characterized by high
blood pressure and damage to organ systems, often the kidneys and
liver. Affecting up to 8% of pregnancies worldwide, preeclampsia
can pose significant risks to both the mother and baby, including
risk of stroke, placental abruption, progression to elecampane,
premature delivery, and death. Symptoms may include severe
headaches, vision changes, upper abdominal pain and swelling in the
hands and face. Delivery of the baby, often very prematurely, is
the only available option for stopping the progression of
preeclampsia. Women who have had preeclampsia have three to four
times the risk of high blood pressure and double the risk for heart
disease and stroke.
About DM199 (rinvecalinase alfa)
DM199 is a recombinant (synthetic) form of human tissue
kallikrein-1 (rhKLK1) in clinical development for acute ischemic
stroke (AI) and preeclampsia. KLK1 is a serine protease enzyme that
plays an important role in the regulation of diverse physiological
processes via a molecular mechanism that increases production of
nitric oxide, prostacyclin and endothelium-derived hyperpolarizing
factor. In the case of AI, DM199 is intended to enhance blood flow
and boost neuronal survival in the ischemic penumbra by dilating
arterioles surrounding the site of the vascular occlusion and
inhibition of apoptosis (neuronal cell death) while also
facilitating neuronal remodeling through the promotion of
angiogenesis. In preeclampsia, DM199 is intended to lower blood
pressure, enhance endothelial health and improve perfusion to
maternal organs and the placenta.
About DiaMedica Therapeutics Inc.
DiaMedica Therapeutics Inc. is a clinical stage
biopharmaceutical company committed to improving the lives of
people suffering from serious ischemic diseases with a focus on
acute ischemic stroke and preeclampsia. DiaMedica’s lead candidate
DM199 is the first pharmaceutically active recombinant (synthetic)
form of the KLK1 protein, an established therapeutic modality in
Asia for the treatment of acute ischemic stroke and other vascular
diseases. For more information visit the Company’s website at
www.diamedica.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the U.S. Private Securities Litigation Reform Act of
1995 and forward-looking information that are based on the beliefs
of management and reflect management’s current expectations. When
used in this press release, the words “anticipates,” “believes,”
“continue,” “could,” “estimates,” “expects,” “intends,” “may,”
“plans,” “potential,” “should,” “can,” or “will,” the negative of
these words or such variations thereon or comparable terminology,
and the use of future dates are intended to identify
forward-looking statements and information. The forward-looking
statements and information in this press release include statements
regarding the Company’s planned clinical expansion into
preeclampsia, the planned DM199 Phase 2 trial for preeclampsia, the
receipt of regulatory approvals for such trial, the timing and
costs of such trial, enrollment in such trial, and anticipated
clinical benefits and success of DM199. Such statements and
information reflect management’s current view and DiaMedica
undertakes no obligation to update or revise any of these
statements or information. By their nature, forward-looking
statements involve known and unknown risks, uncertainties and other
factors which may cause actual results, performance or
achievements, or other future events, to be materially different
from any future results, performance or achievements expressed or
implied by such forward-looking statements. Applicable risks and
uncertainties include, among others, risks and uncertainties
relating to the planned clinical expansion into preeclampsia and
the planned DM199 Phase 2 trial for preeclampsia; uncertainties
relating to the timing of site activations and enrollment,
regulatory applications and related filing and approval timelines;
the possibility of additional future adverse events associated with
or unfavorable results from the ReMEDy2 trial; the possibility of
unfavorable results from DiaMedica’s ongoing or future clinical
trials of DM199; the risk that existing preclinical and clinical
data may not be predictive of the results of ongoing or later
clinical trials; DiaMedica’s plans to develop, obtain regulatory
approval for and commercialize its DM199 product candidate for the
treatment of acute ischemic stroke and preeclampsia and its
expectations regarding the benefits of DM199; DiaMedica’s ability
to conduct successful clinical testing of DM199 and within its
anticipated parameters, enrollment numbers, costs and timeframes;
the adaptive design of the ReMEDy2 trial and the possibility that
the targeted enrollment and other aspects of the trial could change
depending upon certain factors, including additional input from the
FDA and the blinded interim analysis; the perceived benefits of
DM199 over existing treatment options; the potential direct or
indirect impact of COVID-19, hospital and medical facility staffing
shortages, and worldwide global supply chain shortages on
DiaMedica’s business and clinical trials, including its ability to
meet its site activation and enrollment goals; DiaMedica’s reliance
on collaboration with third parties to conduct clinical trials;
DiaMedica’s ability to continue to obtain funding for its
operations, including funding necessary to complete current and
planned clinical trials and obtain regulatory approvals for DM199
for acute ischemic stroke and preeclampsia, and the risks
identified under the heading “Risk Factors” in DiaMedica’s annual
report on Form 10-K for the fiscal year ended December 31, 2023 and
subsequent reports filed with the U.S. Securities and Exchange
Commission, including its most recent quarterly report on Form 10-Q
for the quarterly period ended March 31, 2024. The forward-looking
information contained in this press release represents the
expectations of DiaMedica as of the date of this press release and,
accordingly, is subject to change after such date. Readers should
not place undue importance on forward-looking information and
should not rely upon this information as of any other date. While
DiaMedica may elect to, it does not undertake to update this
information at any particular time except as required in accordance
with applicable laws.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240626456181/en/
Scott Kellen Chief Financial Officer Phone: (763) 496-5118
skellen@diamedica.com
Paul Papi Corporate Communications Phone: (508) 444-6790
ppapi@diamedica.com
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