DJ Imara reports Phase 2a clinical trial results of IMR-687 in adult patients with sickle cell disease
Arix Bioscience PLC (ARIX)
Imara reports Phase 2a clinical trial results of IMR-687 in adult patients
with sickle cell disease
06-Jan-2021 / 14:00 GMT/BST
Dissemination of a Regulatory Announcement, transmitted by EQS Group.
The issuer is solely responsible for the content of this announcement.
Arix Bioscience plc
Imara reports Phase 2a clinical trial results of IMR-687 in adult patients
with sickle cell disease
LONDON, 06 January 2021: Arix Bioscience plc ("Arix", LSE: ARIX), a global
venture capital company focused on investing in and building breakthrough
biotech companies, notes that its portfolio company, Imara Inc. (Nasdaq:
IMRA), today reported results from its Phase 2a clinical trial of IMR-687 in
adult patients with sickle cell disease.
Overall, the data from the Phase 2a clinical trial demonstrated that IMR-687
was well tolerated as a monotherapy and in combination with hydroxyurea at
all dose levels. In the second half of 2021, Imara expects to report interim
Phase 2b data from ongoing clinical trials in sickle cell disease and
beta-thalassemia.
The announcement can be accessed on Imara's website at
https://imaratx.gcs-web.com/press-releases [1] and full text of the
announcement from Imara is contained below.
[ENDS]
Enquiries
For more information on Arix, please contact:
Arix Bioscience plc
Charlotte Parry, Head of Investor Relations
+44 (0)20 7290 1072
charlotte@arixbioscience.com
Optimum Strategic Communications
Supriya Mathur, Shabnam Bashir, Manel Mateus
+44 (0)20 3922 1906
optimum.arix@optimumcomms.com
About Arix Bioscience plc
Arix Bioscience plc is a global venture capital company focused on investing
in and building breakthrough biotech companies around cutting-edge advances
in life sciences.
We collaborate with exceptional entrepreneurs and provide the capital,
expertise and global networks to help accelerate their ideas into important
new treatments for patients. As a listed company, we are able to bring this
exciting growth phase of our industry to a broader range of investors.
For more information please visit: www.arixbioscience.com [2]
Imara Reports Phase 2a Clinical Trial Results of IMR-687 in Adult Patients
with Sickle Cell Disease
Promising reductions in rate of VOCs/SCPCs observed in monotherapy IMR-687
treated patients vs. placebo
Biomarker data from both monotherapy IMR-687 and combination IMR-687+HU
groups show improvement in markers of hemolysis with variable HbF results
Reductions in hsCRP and NTproBNP in monotherapy IMR-687 treated patients
suggest potential for lowering inflammation and cardiac stress in SCD
IMR-687 was well tolerated as a monotherapy and in combination with
hydroxyurea
Additional data from Phase 2a open label extension trial and interim results
from Ardent and Forte Phase 2b clinical trials expected in 2021
BOSTON, Jan. 06, 2021 -- Imara Inc. (Nasdaq: IMRA), a clinical-stage
biopharmaceutical company dedicated to developing and commercializing novel
therapeutics to treat patients suffering from rare inherited genetic
disorders of hemoglobin (Hb), today reported results from its Phase 2a
clinical trial of IMR-687 in adult patients with sickle cell disease (SCD).
"I am encouraged by the incremental data from this readout, especially in
light of the COVID-19 pandemic challenges," said Biree Andemariam, M.D.,
Associate Professor at UConn School of Medicine, Director of the New England
Sickle Cell Institute at UConn Health and lead investigator for the Phase 2a
trial. "This includes a favorable safety profile of IMR-687, lower rate of
VOCs/SCPCs and VOC-related hospitalizations in the Population A1 monotherapy
arm and improvements in several biomarker results across both the
monotherapy and combination groups. I am also pleased by the reductions in
hsCRP and NT-proBNP in the Population A1 monotherapy arm. Both are
clinically utilized biomarkers of inflammation and cardiac stress,
respectively, and suggest that higher doses of IMR-687 may have novel
anti-inflammatory and cardiovascular benefits in sickle cell disease."
"I would like to thank the patients, sickle cell disease community, and
healthcare providers for their participation in this trial, particularly
because the COVID-19 pandemic reduced access to clinical centers," said
Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara. "These
incremental Phase 2a results start an important year of data readouts at
Imara. In the first quarter of 2021, we plan to report updates from our
Phase 2a open label extension trial, including results on 10-15 patients. In
the second half of 2021, we expect to report interim data from our ongoing
higher dose Ardent and Forte Phase 2b clinical trials in sickle cell disease
and beta-thalassemia, respectively."
The Phase 2a clinical trial included a total of 93 treated patients across
four different sub-studies and was designed to evaluate the safety,
tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical
outcomes of escalating doses of IMR-687 administered once daily for 16 to 24
weeks, either as a monotherapy or in combination with hydroxyurea (HU).
Overall, the data from the Phase 2a clinical trial demonstrated that IMR-687
was well tolerated as a monotherapy and in combination with HU at all dose
levels. There were no observed clinically significant shifts in vital signs
or electrocardiogram data, including no hypotension or neutropenia in either
the monotherapy or combination arms. Interim data on patients from
Populations A and B were previously disclosed, with results from the A1 and
B1 populations being reported for the first time.
Monotherapy Sub-studies (A/A1):
Population A (n=40): Patients received either placebo or IMR-687 at
once-daily doses of 50 mg or 100 mg through 12 weeks and then higher doses
of 100 mg or 200 mg, respectively, through an additional 12 weeks (24 weeks
total).
Population A1 (n=18): Patients received either placebo or IMR-687 at a
once-daily dose of 100 mg through 4 weeks and then 200 mg through an
additional 20 weeks (24 weeks total).
Combination Sub-studies (B/B1):
Population B (n=21): Patients received either placebo or IMR-687 once-daily
at 50 mg on top of a stable dose of standard of care HU, with escalation
after 4 weeks to 100 mg for an additional 12 weeks (16 weeks total).
Population B1 (n=14): Patients received either placebo or IMR-687 once-daily
at 50 mg on top of a stable dose of standard of care HU, with escalation
after 4 weeks to 100 mg for an additional 20 weeks (24 weeks total).
Population A1 (monotherapy)
The most frequent adverse events in the IMR-687 treatment arm included
sickle cell anemia with crisis, nausea, headache and back pain and were
generally consistent with those observed at two previously reported interim
analyses. A 25% lower rate of vaso-occlusive crises/sickle cell-related pain
crises (VOCs/SCPCs), as part of the safety analysis, was observed in the
IMR-687 treatment group when compared to placebo. 58% of patients (7 of 12,
9 events total) experienced at least one VOC/SCPC in the IMR-687 treatment
group as compared to 83% (5 of 6, 14 events total) in the placebo
population. Furthermore, the rate of VOC-related hospitalizations was lower
in the IMR-687 treatment group when compared to placebo. 33% of patients (4
of 12) experienced one VOC-related hospitalization in the IMR-687 treatment
group as compared to 66% (4 of 6) in the placebo population.
Biomarker results showed no meaningful changes in F-cells, fetal hemoglobin
(HbF) levels, or Hb levels from baseline through week 24. However, a
dose-dependent increase in HbF (1.3% absolute increase) was seen when
patients dose escalated from 100 mg to 200 mg, starting after 4 weeks and
through 24 weeks. One of seven evaluable patients (14%) in Population A1
recorded an absolute increase in HbF percentage from baseline of greater
than 1% (increase of 3.2%). Markers of hemolysis that include percent
reticulocytes, absolute reticulocyte count, indirect bilirubin and LDH all
improved from baseline in a dose dependent manner, with the greatest
improvement occurring when patients were on the 200 mg dose. This trend
similarly occurred with high sensitivity C-reactive protein (hsCRP) and
amino-terminal pro-brain type natriuretic peptide (NT-proBNP) values.
Placebo patients from Population A1 did not have evaluable week 24 PD
biomarker results due in part to missing study visits and are therefore not
included in the table below. A summary of the mean results from the IMR-687
treatment arm are as follows:
Measure Baseline Week 24 Percent Change from
Value Value Baseline to Week 24
HbF percentage (%) 8.8 8.7 -1.1%
F-cell percentage 28.1 28.5 1.4%
(%)
Hb (g/dL) 8.8 8.6 -2.3%
Markers of Hemolysis
Percent 10.4 7.4 -28.8%
reticulocytes (%)
Absolute 296 240 -18.9%
reticulocyte count
(?-109/L)
Indirect bilirubin 61.4 44.0 -28.3%
(µmol/L)
LDH (IU/L) 397 346 -12.8%
Markers of Inflammation & Cardiac Stress
hsCRP (mg/L) 10.4 2.5 -75.9%
NTproBNP (ng/L) 685 414 -39.6%
Population B1 (combination therapy)
The most frequent adverse events in the IMR-687+HU treatment arm included
headache, sickle cell anemia with crisis and nausea and were generally
consistent with those observed in Population A1. There were no meaningful
differences in VOCs/SCPCs or VOC related hospitalizations, between the
IMR-687+HU and HU+placebo groups.
Biomarker results in IMR-687+HU treated patients showed an overall increase
in F-cells and HbF levels from baseline to week 24, while Hb levels did not
meaningfully change. Three of the eight evaluable subjects (33%) had
absolute increases in HbF percentage of greater than 1%, with a mean
absolute increase in HbF percentage of 4.3% in that subset of patients. Dose
dependent improvements in several markers of hemolysis were observed from
baseline through week 24, with the greatest improvement occurring when
patients were on the 100 mg dose. hsCRP and NT-proBNP values through week 24
slightly increased from baseline. There was a single placebo patient from
Population B1, as other patients did not have evaluable week 24 PD biomarker
data due in part to missing study visits. Therefore, this single patient is
not included in the table below. A summary of the mean results from the
IMR-687+HU treatment arm are as follows:
Measure Baseline Week 24 Percent Change
Value Value from
Baseline to Week
24
HbF percentage (%) 18.6 19.8 6.5%
F-cell percentage (%) 58.8 61.4 4.4%
Hb (g/dL) 9.5 9.4 -1.1%
Markers of Hemolysis
Reticulocytes (%) 7.5 5.3 -29.3%
Absolute reticulocyte 185 137 -25.9%
count (?-109/L)
Indirect bilirubin 34.9 37.9 8.6%
(µmol/L)
LDH (IU/L) 351 340 -3.1%
Markers of Inflammation & Cardiac Stress
hsCRP (mg/L) 11.5 12.5 8.7%
NTproBNP (ng/L) 284 317 11.6%
Population A/B (monotherapy, combination therapy)
Imara previously reported interim results within Populations A and B.
Subsequently, four additional patients completed 24 weeks of dosing in the
Population A monotherapy arm. A completers analysis in this group showed
that the high dose of IMR-687 (100 mg/200 mg) resulted in a relative
increase in F-cell percentage of 13.3% from baseline (p=0.025) and a mean
absolute increase in HbF percentage from baseline of 0.9%. Three of the
eight evaluable subjects (38%) in Population A recorded absolute HbF
percentage increases of greater than 1%, with a mean absolute increase in
HbF percentage of 3.1% in that subset of patients.
In Population B, we examined the PK of IMR-687+HU as compared to HU alone.
The PK data in the second interim analysis indicated that treatment with
IMR-687+HU did not result in changes in HU PK.
Imara anticipates that it will present additional study details at a future
medical meeting.
About IMR-687
IMR-687 is a highly selective and potent small molecule inhibitor of PDE9.
PDE9 uniquely degrades cyclic guanosine monophosphate (cGMP), an active
signaling molecule that plays a role in vascular biology. Lower levels of
cGMP are often found in people with sickle cell disease and beta-thalassemia
and are associated with impaired blood flow, increased inflammation, greater
cell adhesion and reduced nitric oxide-mediated vasodilation.
Blocking PDE9 acts to increase cGMP levels, which are associated with
reactivation of fetal hemoglobin, or HbF, a natural hemoglobin produced
during fetal development. Increased levels of HbF in red blood cells have
been demonstrated to improve symptomology and lower disease burden in
patients with sickle cell disease and patients with beta-thalassemia.
About Imara
Imara Inc. is a clinical-stage biotechnology company dedicated to developing
and commercializing novel therapeutics to treat patients suffering from rare
inherited genetic disorders of hemoglobin. Imara is currently advancing
IMR-687, a highly selective, potent small molecule inhibitor of PDE9 that is
an oral, once-a-day, potentially disease-modifying treatment for sickle cell
disease and beta-thalassemia. IMR-687 is being designed to have a multimodal
mechanism of action that acts on red blood cells, white blood cells,
adhesion mediators and other cell types. For more information, please visit
www.imaratx.com [3].
Cautionary Note Regarding Forward-Looking Statements
Statements in this press release about future expectations, plans and
prospects, as well as any other statements regarding matters that are not
historical facts, may constitute "forward-looking statements" within the
meaning of The Private Securities Litigation Reform Act of 1995. These
statements include, but are not limited to, statements relating to the (i)
plan to release additional data on the Phase 2a clinical trial of IMR-687 in
patients with sickle cell disease, (ii) content of, and timing with respect
to, the reporting of data from the open label extension clinical trial
evaluating IMR-687 in patients with sickle cell disease, (iii) clinical
trial design and timing with respect to reporting of data from the Ardent
and Forte Phase 2b clinical trials in patients with sickle cell disease and
beta-thalassemia and (iv) the Company's beliefs regarding the strength of
its clinical data, the tolerability and therapeutic potential of IMR-687 and
advancement of its clinical program. The words "anticipate," "believe,"
"continue," "could," "estimate," "expect," "intend," "may," "plan,"
"potential," "predict," "project," "should," "target," "will," "would" and
similar expressions are intended to identify forward-looking statements,
although not all forward-looking statements contain these identifying words.
Actual results may differ materially from those indicated by such
forward-looking statements as a result of various important factors,
including the impact of extraordinary external events, such as the risks and
uncertainties resulting from the impact of the COVID-19 pandemic on the
Company's business, operations, strategy, goals and anticipated milestones,
including its ongoing and planned research activities and ability to conduct
and readout data from its ongoing clinical trials of IMR-687; the Company's
ability to advance the development of IMR-687 under the timelines it
projects in current and future clinical trials, demonstrate in any current
and future clinical trials the requisite safety and efficacy of IMR-687,
replicate scientific and non-clinical data in both subsequent case report
readouts and in clinical trials and other factors discussed in the "Risk
Factors" section of the Company's most recent Quarterly Report on Form 10-Q,
which is on file with the Securities and Exchange Commission and in other
filings that the Company makes with the Securities and Exchange Commission
in the future. Any forward-looking statements contained in this press
release speak only as of the date hereof, and the Company expressly
disclaims any obligation to update any forward-looking statement, whether as
a result of new information, future events or otherwise.
Media Contact:
Gina Nugent
Ten Bridge Communications
617-460-3579
gina@tenbridgecommunications.com
Investor Contact:
Michael Gray
617-835-4061
mgray@imaratx.com
ISIN: GB00BD045XXX
Category Code: MSCU
TIDM: ARIX
LEI Code: 213800OVT3AHQCXNIX43
OAM Categories: 3.1. Additional regulated information required to be
disclosed under the laws of a Member State
Sequence No.: 90965
EQS News ID: 1158842
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January 06, 2021 09:00 ET (14:00 GMT)
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