Imara Announces FDA Clearance of Investigational New Drug Application (IND) for Tovinontrine (IMR-687) for Heart Failure with Preserved Ejection Fraction (HFpEF)

Expanding patient base and potential of Imara’s small molecule oral inhibitor of phosphodiesterase-9 (PDE9) alongside hemoglobin disorders

Phase 2 trial aims to select HFpEF patients with enriched PDE9 expression
for targeted approach to a heterogeneous disease

Study initiation planned for second quarter of 2022

BOSTON, Jan. 25, 2022 (GLOBE NEWSWIRE) --  Imara Inc. (Nasdaq: IMRA), a clinical-stage biopharmaceutical company dedicated to developing and commercializing novel therapeutics to treat patients suffering from rare hemoglobin disorders and other serious diseases, today announced that the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for tovinontrine (IMR-687) to commence clinical development for the treatment of heart failure with preserved ejection fraction (HFpEF). Imara plans to initiate a Phase 2 trial in the second quarter of 2022 to evaluate tovinontrine in patients 45 years of age or older with persistent HFpEF symptoms.

“We are excited to bring our deep expertise in clinical development and operations to patients suffering from HFpEF,” said Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara. “We expect to initiate the Phase 2 trial in the second quarter of 2022, with a design that focuses on identifying HFpEF patients with high PDE9 expression, creating a targeted approach in this prevalent disease. With tovinontrine we believe we have the best-in-class PDE9 inhibitor for evaluation in this patient population, with in vitro data demonstrating superior potency and selectivity, as well as minimal brain penetration when compared to other PDE9 inhibitors.”

“The preclinical data strongly support moving tovinontrine into clinical testing for patients with HFpEF,” said Deepak Gupta, M.D., M.S.C.I, Assistant Professor of Medicine at Vanderbilt University Medical Center’s Division of Cardiovascular Medicine. “Study inclusion criteria, such as increased left ventricular hypertrophy and elevated N-terminal pro b-type natriuretic peptide, or NT-proBNP levels, enrich for patients with higher PDE9 expression, making this a selective proof-of-concept approach.”

Imara’s Phase 2 HFpEF trial will be a randomized, placebo-controlled study of approximately 170 patients 45 years of age or older with enriched PDE9 expression and persistent symptoms of HFpEF. Trial subjects will be dosed for 16 weeks. The primary endpoint will be change in NT-proBNP, with secondary endpoints that include safety and tolerability as well as quality of life measures such as Kansas City Cardiomyopathy Questionnaire (KCCQ) and New York Heart Association (NYHA) classification. Exploratory measures include a clinical composite score, 6-minute walk test and evaluation of cardiac structure and function.

In addition to Imara’s internal development team, led by cardiologist Toni Bransford, M.D., Vice President of Clinical Development, this trial will be overseen by an executive committee of key opinion leaders in heart failure including: Deepak Gupta, M.D., M.S.C.I. (chair), Assistant Professor of Medicine at Vanderbilt University Medical Center’s Division of Cardiovascular Medicine; Maggie Redfield, M.D., Division of Circulatory Failure, Department of Cardiovascular Medicine and Professor of Medicine at the Mayo Clinic; Sanjiv Shah, M.D., Director, Institute for Augmented Intelligence in Medicine - Center for Deep Phenotyping and Precision Therapeutics and Professor of Medicine (Cardiology) Northwestern University; and Thomas Wang, M.D., Professor and Chair of the Department of Internal Medicine at UT Southwestern Medical Center.

About Heart Failure with Preserved Ejection Fraction
Heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure, is typically caused by abnormalities of cardiac filling, which leads to symptoms such as shortness of breath, exercise intolerance and fluid retention. HFpEF is the most common form of heart failure; hospitalization rates are similar to heart failure with reduced ejection fraction (HFrEF, or systolic heart failure), but with fewer treatment options to improve symptoms and outcomes.

About Tovinontrine (IMR-687) 
Tovinontrine is a highly selective and potent small molecule inhibitor of phosphodiesterase-9 (PDE9). PDE9 selectively degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology and hemoglobin production. Lower levels of cGMP are found in people with sickle cell disease (SCD) and beta-thalassemia and are associated with reduced blood flow, increased inflammation, greater cell adhesion and reduced nitric oxide mediated vasodilation. Blocking PDE9 acts to increase cGMP levels, which is associated with several benefits including the potential reactivation of fetal hemoglobin (HbF), a natural hemoglobin produced during fetal development. Increased levels of HbF in RBCs have been demonstrated to improve symptomatology and substantially lower disease burden in both patients with SCD and patients with beta-thalassemia. Levels of cGMP are also often reduced in patients with heart failure. Augmenting cGMP through the natriuretic peptide-cGMP pathway has been shown to mediate cardioprotective effects that lead to reduced heart failure disease progression and fewer events.

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 and other serious diseases. Imara is advancing tovinontrine (IMR-687), a highly selective, potent small molecule inhibitor of PDE9 that is an oral, potentially disease-modifying treatment currently in clinical development for sickle cell disease, beta-thalassemia and heart failure with preserved ejection fraction (HFpEF). Imara is also advancing IMR-261, an oral activator of nuclear factor erythroid 2–related factor 2, or Nrf2. For more information, please visit www.imaratx.com.

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 Company’s clinical developments plans and timeline for tovinontrine (IMR-687) in HFpEF and beliefs regarding the therapeutic potential of tovinontrine. 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, 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.

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