CAMBRIDGE, Mass.--(EON: Enhanced Online News)--Imara Inc., a biotechnology company dedicated to developing novel therapeutics for patients with sickle cell disease (SCD) and other hemoglobinopathies, presented results of preclinical studies of its lead product candidate IMR-687, a potent PDE9 inhibitor, in sickle cell disease at the 2016 American Society of Hematology Annual Meeting (ASH) in San Diego.
“A drug such as IMR-687, which has the potential to replace hydroxyurea (HU) with fewer side effects, would likely increase medication adherence and may provide practice-changing implications for patients.”
“Sickle cell disease is a devastating condition effecting hundreds of thousands of patients worldwide. Despite currently approved therapies, there remains a serious medical need for more effective and less toxic treatment options,” said James McArthur, Ph.D., founder, President, and Chief Executive Officer of Imara. “We are encouraged by these positive preclinical results which provided the support to initiate our Phase 1 study of IMR-657 which we announced last month.”
“It is of utmost importance that we work together to advance new therapies to improve outcomes and quality of life for individuals living with sickle cell disease,” said Julie Kanter, director of the Sickle Cell Research Program at the Medical University of South Carolina. “A drug such as IMR-687, which has the potential to replace hydroxyurea (HU) with fewer side effects, would likely increase medication adherence and may provide practice-changing implications for patients.”
The presentation described preclinical studies demonstrating that IMR-687 was as potent as HU, an approved therapy for sickle cell disease, in multiple human cell and animal models of sickle cell disease in decreasing the red blood cell and white blood cell pathologies of the disease. The cumulative results of these studies indicated the following:
- In an escalating dose study in K562 erythroid cells, IMR-687 induced higher levels of cGMP than HU at 6 hours at a much lower drug concentration, suggesting a more favorable therapeutic profile than currently approved therapies.
- In the Berkeley mouse model of SCD, IMR-687 treatment increased fetalglobin (HbF) expression and decreased the percent of sickled red blood cells (RBC), decreased plasma bilirubin, splenomegaly and leukocytosis.
- In the Townes mouse model of SCD, IMR-687 significantly reduced microvascular occlusion, a cause of organ damage and pain, increased HbF expression, and reduced the percentage of sickled RBCs, and reduced leukocytosis.
- IMR-687 was safe and well tolerated in long term safety toxicology preclinical safety studies and importantly demonstrated low brain exposure of IMR-687 reducing the risk of inhibiting neuronal PDE9. Consistent with this finding, no fear conditioning response changes were noted with dosing of IMR-657 in contrast to those treated with another PDE9 inhibitor with brain penetration characteristics.
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.
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 initial funding from life science investors NEA, Pfizer Venture Investments, Lundbeckfond Ventures, Bay City Capital and Alexandria Venture Investments.