- DM199 Met Primary Safety and Tolerability Endpoints in
ReMEDy Study Top-Line Data
- Demonstrated Therapeutic Effect in Participants Not
Pre-Treated With Mechanical Thrombectomy
- Reduced Risk of Recurrent Stroke
- Results Consistent With Clinical Studies of Approved Urinary
Derived KLK1 in China
- Improvement in eGFR for Pre-Defined Chronic Kidney Disease
Sub-Group
Company to discuss top-line data during its
scheduled first quarter financial results conference call tomorrow
at 8:00 am Eastern Time
DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage
biopharmaceutical company developing novel treatments for
neurological disorders and chronic kidney disease, announced today
that DM199, a drug intended to restore KLK1 levels and the body’s
natural ability to regulate blood flow and reduce inflammation
after an acute ischemic stroke (AIS), met primary safety and
tolerability endpoints in the ReMEDy phase II study. Further, no
DM199-related serious adverse events were noted in the study.
According to top-line phase II results, there was also a
demonstrated therapeutic effect in participants who received tissue
plasminogen activator (tPA) prior to enrollment, but not in
participants receiving mechanical thrombectomy.
The ReMEDy study enrolled 92 participants to assess DM199, a
recombinant form of human tissue Kalikrein-1 (KLK1), a serine
protease, or protein, which plays a critical role in local blood
flow regulation and in reducing inflammation, in the treatment of
participants who experienced an AIS. AIS occurs when a clot blocks
blood flow through a brain artery and represents approximately 85%
of all strokes in the United States. According to the U.S. Centers
for Disease Control and Prevention (CDC), there are approximately
690,000 acute ischemic strokes in the United States annually, one
quarter of which are recurrent strokes, or strokes occurring in
people who have had a previous stroke.
Ninety-one (91) of the 92 ReMEDy study enrolled participants
were evaluable for safety in this multi-center, double-blind,
randomized, placebo-controlled study. Participants were enrolled
within 24 hours of stroke symptom onset and received an initial
administration of DM199 or placebo as an intravenous infusion,
followed by subcutaneous injections every three days over the
following three weeks.
Prior to enrollment, 44 of the 91 evaluable patients (48%)
received a mechanical thrombectomy, a treatment indicated for those
who have a large vessel occlusion and can be treated within six to
24 hours of the onset of stroke symptoms. While approximately 20%
of AIS patients are believed to be eligible for a mechanical
thrombectomy, currently only about 5 to 10% receive the treatment
due to elapsed time post stroke or unavailability of the therapy at
the hospital where they present. DM199 is intended to treat the
approximately 90% of AIS patients who do not receive either
mechanical thrombectomy or tPA. Treatment for these patients is
limited to palliative therapies.
Due to the large volume of participants receiving mechanical
thrombectomy prior to enrollment in the study (48%) and a
disproportionate distribution between the active treatment and
placebo groups, DM199 did not produce a therapeutic effect in the
overall study analysis.
When participants treated with mechanical thrombectomy are
excluded from the study data set, representing the group of
participants most closely aligned with the target treatment
population for DM199 noted above, a positive therapeutic effect was
demonstrated. As shown in the table below, when evaluating the
participants treated with DM199 (n=25) vs. palliative therapies
and/or tPA (n=21), the results showed that 36% of participants
receiving DM199 progressed to a full or nearly full recovery at 90
days (NIHSS: 0-1), compared to 14% of participants in the placebo
group. This represents a 22% increase in the proportion of
participants achieving a full or nearly full recovery.
Additionally, subject deaths decreased from 24% in the placebo
group to 12% in the active therapy group, a 50% reduction.
DM199 vs. Palliative Therapies and/or
tPA
NIHSS Outcomes at 90
Days
0-1
2-8
≥ 9
Death
Placebo (n=21)
14%
57%
5%
24%
DM199 (n=25)
36%
36%
16%
12%
In addition, in the evaluable participants (n=91), a significant
reduction in the number of participants with severe recurrent
stroke was noted in the active treatment group: 1 (2%) patient
treated with DM199 vs. 7 (16%) on placebo (p=0.028), with 4 of the
7 on placebo resulting in participant death.
Further, in reviewing evaluable participants (n=91),
improvements in the following biomarkers were observed in
participants treated with DM199, which the Company believes are
consistent with the DM199 mechanism of action:
- Increased nitric oxide (+105%) and prostaglandin E2 (+54%) were
observed at day 22 vs baseline (p<0.05). Placebo group was not
statistically significant vs baseline (p>0.05). These changes
noted in the active treatment group did not reach statistical
significance compared to placebo.
- Reduction in C-reactive protein (CRP) of (-70%), a blood marker
of inflammation, at 90 days. CRP decreased significantly vs.
baseline (p<0.05), but was not statistically significant vs.
placebo. The change in the placebo group was not statistically
significant vs. baseline (p>0.05).
- Reduction in elevated glucose levels in participants with type
2 diabetes, as defined by a blood glucose level >7 mmol/L
(n=14), an average decrease of 1.9 mmol/L (p=0.06) in blood glucose
levels of participants on active therapy was observed at day 22. In
comparison, participants in the placebo group (n=16) showed an
average increase of 0.08 mmol/L (p=0.94) at day 22.
DiaMedica is also developing DM199 for the treatment of chronic
kidney disease (CKD). Accordingly, changes in the estimated
glomerular filtration rate (eGFR), a measure of kidney function,
were analyzed in participants with eGFR <70 mL/Min/1.732 at
baseline, which indicates the presence of CKD. Participants
receiving DM199 exhibited a marked increase in eGFR at days 22
(last dose) and 56 (34 days post-treatment), as shown in the table
below. Further the Company noted that eGFR at day 22 increased by
at least 2 mL/Min in 77% of DM199 participants compared to 20% in
placebo (p=0.007). DM199 is currently being evaluated in the REDUX
phase II study for CKD.
eGFR Mean Δ from Baseline
(mL/Min/1.732)
Day 22 (Last Dose)
Day 56 (Off Treatment)
Placebo
+0.84 (n=15)
-0.24 (n=12)
DM199
+7.5 (n=13)
+5.8 (n=12)
Group Difference
+6.6
+6.1
“These findings are consistent with Chinese data on the
urine-derived form of KLK1 and provide a signal that recombinant
human KLK1 appears safe and may have promise as a new tool for
physicians who have limited options for the treatment of patients
suffering acute ischemic stroke,” said Professor Bruce Campbell,
BMedSc, PhD, FRACP, FAHMS Neurologist, Head of Stroke Department of
Neurology at the Royal Melbourne Hospital.
DiaMedica’s President and CEO, Rick Pauls, said: “Very few
patients have a treatment option for AIS today. Approximately 10%
of patients receive tPA or mechanical thrombectomy and we are
developing DM199, with a 24 hour therapeutic treatment window, to
significantly expand the proportion of patients who have access to
effective and safe treatment.” Mr. Pauls continued, “It’s also very
encouraging to see data suggesting that DM199 treatment may
mitigate the adverse impact of ischemic stroke on kidney function,
a significant but poorly understood comorbidity in many stroke
victims.”
The detailed results of the ReMEDy trial has been accepted for
E-Poster discussion at the joint European Stroke Organisation and
World Stroke Organization Conference (ESO-WSO 2020), to be held in
Vienna, Austria on November 7, 2020 and will also be submitted for
publication.
DiaMedica intends to request a meeting with the FDA to define
the development program leading to a path to commercialization for
acute ischemic stroke.
Conference call and webcast information
DiaMedica will host a live conference call and webcast on
Thursday May 14, 2020 at 7:00 am Central Time to discuss the
top-line phase II data.
Conference Call details:
Date:
Thursday, May 14, 2020
Time:
7:00 AM CT / 8:00 AM ET
Web access:
https://event.on24.com/wcc/r/2158468/5BAA62D375A1F892573859D379BAF858
Dial In:
(833) 502-0492 (domestic)
(778) 560-2558
(international)
Conference ID:
8757888
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 play back on DiaMedica’s website, under
investor events and presentations, following the earnings call and
for 12 months thereafter. A telephonic replay of the conference
call will be available until May 21, 2020, by dialing (800)
585-8367 (US Toll Free), (416) 621-4642 (International), replay
passcode 8757888.
About DM199
DM199 is a recombinant (synthetic) form of the human serine
protease, KLK1. The KLK1 protein plays an important role in the
regulation of diverse physiological processes including blood flow,
inflammation, fibrosis, oxidative stress and neurogenesis via a
molecular mechanism that increases production of nitric oxide and
prostaglandin. KLK1 deficiency may play a role in multiple vascular
and fibrotic diseases such as chronic kidney disease, retinopathy,
stroke, vascular dementia and resistant hypertension where current
treatment options are limited or ineffective. DiaMedica is the
first company to have developed a recombinant form of the KLK1
protein. The KLK1 protein, produced from porcine pancreas and human
urine, has been used to treat patients in Japan, China and Korea
for decades. DM199 is currently being studied in patients with
chronic kidney disease and patients with acute ischemic stroke.
About DiaMedica Therapeutics Inc.
DiaMedica Therapeutics Inc. is a clinical stage
biopharmaceutical company focused on developing novel treatments
for neurological and kidney diseases. DiaMedica’s common shares are
listed on The Nasdaq Capital Market under the trading symbol
“DMAC.”
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 “may,” “expects,” “intends,”
“estimates”, “believes”, “anticipates”, “plans”, “continue,”
“will”, or “should”, 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, but not limited to, the
anticipated clinical benefits and success of DM199; the safety and
efficacy of DM199; the assessment of the data from the ReMEDy study
and the future publication and sharing of the full study results,
and regulatory path forward. 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, the possibility of unfavorable
results from additional clinical trials of DM199 or from subsequent
analysis of existing data from the ReMEDy study or existing or new
data received from additional ongoing and future studies 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 ability to conduct successful clinical testing of DM199
and within its anticipated parameters, costs and timeframes; the
perceived benefits of DM199 over existing treatment options; the
potential direct or indirect impact of the COVID-19 pandemic on
DiaMedica’s business; its reliance on collaboration with third
parties to conduct clinical trials; its ability to continue to
obtain funding for its operations, and the risks identified under
the heading “Item 1.A. Risk Factors” in DiaMedica’s annual report
on Form 10-K for the fiscal year ended December 31, 2019 as filed
with the SEC on March 23, 2020 and subsequent SEC filings by
DiaMedica. 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/20200513005785/en/
Investor Contact Scott Kellen Chief Financial Officer
Phone: (763) 496-5118 skellen@diamedica.com
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