CAMBRIDGE, Mass.--(BUSINESS WIRE)--Imara Inc. today announced it will report additional preclinical and Phase 1 clinical data from the company’s lead compound, IMR-687, a once-daily, oral therapy designed to address the underlying pathology of sickle cell disease (SCD). In preclinical studies, IMR-687’s mechanism of action was shown to positively impact both red and white blood cell pathologies associated with the disease. The company has previously reported the ability of IMR-687 to induce fetal hemoglobin (HbF) in murine and human cells at ASH in 2017. Importantly, the data from a recent Phase 1 clinical trial in healthy volunteers demonstrated IMR-687 to be safe and well-tolerated at the target dose that exceeded the effective doses in cell and animal models of SCD, thereby clearing a path to a Phase 2 study in adult patients with SCD. The new data will be presented at the 6th Annual Sickle Cell Therapeutics Conference in New York.
“Data from our Phase 1 clinical trial demonstrate we are able to safely dose subjects at levels shown to be therapeutically meaningful in preclinical models,” said James McArthur, Ph.D., Founder, President, and Chief Executive Officer of Imara. “We believe IMR-687 could represent an important new treatment option for patients in need. Based on the favorable data to date, we plan to initiate a Phase 2 clinical trial in adult patients by the end of this year.”
In SCD, both red and white blood cells are affected, causing significant pain and severe symptoms with potentially life-threatening consequences. In a preclinical mouse model, IMR-687 reduced red blood cell sickling and white blood cell adhesion associated with the disease. IMR-687 also demonstrated a reduction in blood vessel occlusion, a hallmark of the disease, which causes debilitating pain, organ damage, and early mortality in patients with SCD. Additionally, preclinical studies showed IMR-687 increased fetal hemoglobin (HbF); increases in HbF have been shown to improve symptoms in SCD patients.
Existing treatment options for SCD are limited and there remains a significant unmet need for new treatment options. The majority of patients are treated with pain medications, fluids, and blood transfusions, and experience frequent hospitalizations as a result. The only approved treatments for SCD are hydroxyurea, approved more than a decade ago, and Endari, an oral amino acid L-glutamine powder. Bone marrow or stem cell transplants may be an option for younger patients with severe SCD. However, these treatment options either come with severe and potentially life-threatening side effects or have limited efficacy.
IMR-687 was specifically designed to address the underlying pathology of sickle cell disease. An orally-administered, highly potent and selective phosphodiesterase 9 (PDE9) inhibitor, IMR-687 is a potentially 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. A Phase 1 clinical trial in healthy volunteers showed IMR-687 to be safe and well-tolerated.
IMR-687 has been granted both U.S. Orphan Drug Designation and U.S. Rare Pediatric 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.
Imara Inc., a Cydan Development company, is dedicated to developing novel therapeutics for patients with sickle cell disease. Imara is developing IMR-687, a highly selective, potent small molecule inhibitor of PDE9, to treat patients with sickle cell disease. The company was launched following an 18-month diligence and de-risking scientific collaboration between orphan drug accelerator Cydan Development and H. Lundbeck A/S with $31M Series A funding from life science investors NEA, Pfizer Venture Investments, Lundbeckfond Ventures, Bay City Capital and Alexandria Venture Investments.