Imara Presented Positive, Interim Phase 2a Data on IMR-687 for the Treatment of Sickle Cell Disease at the 24th Congress of the European Hematology Association

Company encouraged by interim 13-week data in trial designed to
assess the safety and tolerability of IMR-687 and explore the potential
efficacy of IMR-687 on clinical outcome measures relevant to sickle cell
disease

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Imara Inc., a clinical-stage biopharmaceutical company developing novel
therapies for people living with sickle cell disease and other serious,
inherited blood disorders, today announced promising interim, 13-week
Phase 2a data on IMR-687, that were presented at the 24^th
Congress of the European Hematology Association (EHA) in Amsterdam.
IMR-687 is an investigational, orally administered, highly potent and
selective phosphodiesterase 9 (PDE9) inhibitor currently being evaluated
as a potential disease-modifying therapeutic for sickle cell disease
(SCD). Data presented at EHA demonstrated that treatment with IMR-687 in
adult patients was generally well tolerated. The data also support the
dual mechanism of action of IMR-687, with activity seen across both red
and white blood cell biomarkers.

“These initial Phase 2a data demonstrate the potential of IMR-687 to
significantly impact key biomarkers associated with the pathology of
this serious disease,” said Biree Andemariam, M.D., Associate Professor
at UConn School of Medicine and Director of the New England Sickle Cell
Institute at UConn Health, and lead investigator for the trial. “In the
laboratory we saw that IMR-687 inhibition of PDE9 increases
intracellular cGMP levels, increases fetal hemoglobin expression,
reduces sickling and hemolysis of red blood cells, and does not induce
neutropenia. The interim Phase 2a data reflect trends that could be
indicative of meaningful clinical translation of these important
measures in SCD.”

The Phase 2a clinical trial is designed to evaluate the safety,
tolerability, pharmacokinetics and pharmacodynamics of escalating doses
of IMR-687 administered once daily for 16 to 24 weeks in two groups of
patients with SCD: those not on hydroxyurea (HU) (Population A) and
those receiving a stable dose of HU according to the current standard of
care (Population B). Blinded white cell markers in Population A (n=19),
along with red cell markers and quality of life measures (ASCQ-Me®)
(n=13) were analyzed. The blinded interim analysis was conducted on the
monotherapy IMR-687 (Population A) subgroup. At 5 weeks, in the 100 mg
dose group of Population A, there was a trend to reduced soluble P
selectin (sPsel), soluble vascular cell adhesion molecule-1 (sVCAM) and
myeloperoxidase (MPO) compared to placebo. At 13 weeks, in the 100 mg
dose group of Population A, there was an increase (110%) in the percent
of F-cells, which are red blood cells that contain fetal hemoglobin
(HbF) which often precede rises in total HbF. A corresponding decrease
in absolute reticulocyte count and the percentage of reticulocytes, with
a trend towards improved pain as measured by ASCQ-Me®, was also observed
at 13 weeks in Population A.

Blinded safety data for 27 patients in the Phase 2a clinical trial
demonstrated that treatment with IMR-687 was generally well tolerated,
with no clinically significant changes in white blood cell counts and no
evidence of neutropenia. There were no treatment-related serious adverse
events.

“We are encouraged by this interim Phase 2a analysis that reinforces our
belief in the potential of IMR-687 as a single oral, once-a-day
therapeutic,” said Rahul D. Ballal, Chief Executive Officer of
Imara. “IMR-687 uniquely targets both red cell and white cell aspects of
the disease, and we are working to expeditiously advance this novel
therapy through clinical development, with a goal of delivering it to
patients with SCD who are in need of innovative treatment options.”

Imara expects to announce additional interim Phase 2a data in the second
half of 2019. Imara anticipates that these data will include safety and
potential activity in additional patients, including patients in
Population A that received higher doses and/or longer treatment duration
with IMR-687 as well as the first data on patients in Population B.

IMR-687 Phase 2a Clinical Trial Design

IMR-SCD-102 is a Phase 2a, randomized, double-blind, placebo-controlled
study of IMR-687. It is designed to evaluate the safety, tolerability,
pharmacokinetics and pharmacodynamics of escalating doses of IMR-687
administered once daily for 16 to 24 weeks in two groups of patients
with SCD: those not on hydroxyurea (HU) (Population A) and those
receiving a stable dose of HU according to the current standard of care
(Population B). Participants in Population A receive either IMR-687 or
placebo for a total of 24 weeks. On Day 1, subjects are randomized in a
1:1:1 ratio to receive oral IMR-687 50 mg, IMR-687 100 mg or placebo
daily for the first 12 weeks. Each participant’s dose is doubled at week
13 following the review of clinical safety data. Participants in
Population B are randomized in a 2:1 ration and receive either a 50 mg
dose of IMR-687 or placebo, with dose escalation to 100 mg (or placebo)
after four weeks and review of the clinical safety data. The Adult
Sickle Cell Quality of Life Measurement Information System (ASCQ-Me®),
is also administered at baseline, 13 weeks and at the end of the study.

About IMR-687

IMR-687 has been designed to address the underlying pathology of sickle
cell disease. An orally administered, highly potent and selective
phosphodiesterase 9 (PDE9) inhibitor, IMR-687 has the potential to be a
disease-modifying therapeutic for sickle cell disease as well as other
hemoglobinopathies. Pre-clinical data demonstrate IMR-687 reduces both
the sickling of red blood cells and blood vessel occlusion that cause
debilitating pain, organ damage, and early mortality in affected
patients. In a Phase 1 clinical trial in healthy volunteers, IMR-687 was
demonstrated to be well-tolerated. IMR-687 is currently in a Phase 2a
clinical trial in patients with sickle cell disease. IMR-687 has been
granted U.S. Orphan Drug Designation, U.S. Rare Pediatric Designation
and Fast Track Designation by the Food and Drug Administration (FDA).

About Sickle Cell Disease

Sickle cell disease is a rare, genetically inherited condition that
alters hemoglobin, the protein in red blood cells that transports oxygen
throughout the body. The altered hemoglobin distorts red blood cells
into a sickle, or crescent, shape. Painful episodes can occur when
sickled red blood cells, which are stiff and inflexible, get stuck in
small blood vessels. These episodes deprive tissues and organs of
oxygen-rich blood and can lead to vaso-occlusive crisis (VOC), acute
chest syndrome (ACS), and permanent damage to organs including the
liver, spleen, kidney and brain.

Sickle cell disease represents a critical unmet medical need globally,
as a rare disease in many parts of the world including in the United
States and as an endemic condition in certain African countries.

About Imara

Imara Inc. is committed to transforming the lives of people with sickle
cell disease and other serious hemoglobinopathies, including beta
thalassemia, by developing oral small molecule therapeutics that are
designed to be easy to administer and use across the world. Imara is
currently advancing IMR-687, a highly selective, potent small molecule
inhibitor of PDE9 with a dual mechanism of action targeting both red and
white blood cells, in an ongoing Phase 2a clinical trial in patients
with sickle cell disease. In March 2019, Imara closed a $63M Series B
with leading life science investors New Enterprise Associates, OrbiMed
Advisors, Arix Bioscience plc, RA Capital, Rock Springs Capital, Pfizer
Venture Investments, Lundbeckfonden Ventures, Bay City Capital and
Alexandria Venture Investments. For more information, please visit www.imaratx.com.

Contacts

Imara Media Contact:
Krystle Gibbs
Ten Bridge
Communications
508-479-6358
[email protected]

Imara Company / Investor Contact:
Michael Gray
857-320-4636
[email protected]