Imara recently presented positive preclinical results of its lead drug candidate IMR-687, a potent PDE9 inhibitor for the treatment of sickle cell disease (SCD). The presentation, which was previewed in a November article, took place at the 2016 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, Calif., Dec. 3-6.
“Sickle cell disease is a devastating condition affecting hundreds of thousands of patients worldwide. Despite currently approved therapies, there remains a serious medical need for more effective and less toxic treatment options,” James McArthur, PhD, founder, president, and chief executive officer of Imara, said in a press release. “We are encouraged by these positive preclinical results, which provided the support to initiate our Phase 1 study of IMR-657,” he said.
“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, MD, 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 ASH presentation, “A Novel, Highly Potent and Selective PDE9 Inhibitor for the Treatment of Sickle Cell Disease,” described the preclinical animal results in which IMR-687 was shown to increase fetal hemoglobin, the major genetic modulator of the hematologic and clinical features of SCD, which prevents the polymerization of the sickled haemoglobin as potently as Hydroxyurea (HU). HU is a chemotherapeutic agent and an approved therapy for SCD.
In addition, the data demonstrated IMR-687’s ability to reduce red cell sickling, reduce red blood cell death and reduce occlusion of blood vessels.
The data also showed that compared to HU, IMR-687 induced higher levels, at a much lower drug concentration, of the enzyme cyclic guanosine monophosphate (cGMP), which mediates vasodilatation and induces greater blood flow.
In this preclinical study, IMR-687 was found to be safe, well-tolerated, with low brain exposure, demonstrating a favorable safety profile. Based on these findings, the research suggests that IMR-687 may offer a once-a-day, oral, safe replacement for HU in the treatment of SCD.
IMR-687 is a highly potent, selective inhibitor of phosphodiesterase-9 (PDE9) in blood cells that reportedly reduces both red blood cell sickling and blockage of blood vessels, the underlying causes of SCD. Imara is moving IMR-687 into human clinical trials.