17th June 2020
Written by
Stay Updated
Add your email below to stay updated with useful and informative content from Arix and our portfolio companies
See also: Imara - Advancing Sickle Cell Therapies
Executive Summary
Background
Imara (Nasdaq: IMRA) is a clinical stage biopharma company developing IMR-687 for the treatment of haemoglobinopathies: Sickle Cell Disease (SCD) and β-Thalassemia. Imara’s goal is to leverage the differentiated mechanism of action, ease of administration and stable drug properties of IMR-687 to potentially serve a broad range of patients suffering from hemoglobinopathies around the world, including those in underserved regions.
SCD is a rare inherited recessive disease most commonly found in patients with African or Caribbean heritage, and affects approximately 100,000 people in the US and 134,000 in Europe, with an estimated 4.4 million patients worldwide. Historically, engagement with healthcare has been low among this patient group, in part due to poor treatment options but also due to broader complex socio-economic reasons. Patients with haemoglobinopathies express mutant versions of β-globin (a key subunit of haemoglobin), which results in unhealthy red blood cells and life changing symptoms in patients. In SCD this includes painful vaso-occlusive crises (VOCs), organ damage (e.g., kidney function loss), stroke, acute chest syndrome and ultimately lower life expectancy.
IMR-687 is an orally delivered, small molecule inhibitor of PDE9, which has been shown in preclinical and clinical studies to induce expression of foetal haemoglobin (HbF). The induction of HbF expression results in the replacement of mutant β-globin with healthy HbF (a version of haemoglobin usually only expressed during foetal development), therefore rescuing the health of the red blood cells.
For years the standard of care in SCD has been hydroxyurea (HU), a chemotherapeutic which induces HbF expression and is considered effective for managing SCD; however, the safety profile, poor tolerability and need for frequent monitoring results in sub-optimal compliance among SCD patients.
Despite the considerable unmet need for novel therapies there has been little innovation in this space until relatively recently, with two drugs approved for SCD in 2019 (Global Blood Therapeutics’ Oxbryta and Novartis’ Adakveo). While these novel therapies are warmly welcomed and will no doubt be helpful for some patients, there remains a critical need for a simple, convenient and tolerable maintenance therapy for SCD. Other highly innovative approaches such as genetically engineered haematopoietic stem cells provide potentially curative options but are unlikely to be available to most patients due to cost and requirement to be healthy enough to tolerate the harsh conditioning regimens but sick enough for this intervention to be appropriate.
25th EHA Annual Congress 2020 – Interim Phase 2a data (Abstract S290)
A second interim analysis of the ongoing randomised, blinded, placebo-controlled study of IMR-687 in adult SCD patients has been conducted and was recently presented at the virtual European Haematology Association (EHA) conference. As prespecified in the protocol, this analysis was performed once 18 patients in Population A (those not receiving HU) had completed 6 months of treatment with IMR-687 (N=5 on 100/200mg; N=7 on 50/100mg) or placebo (N=6). Patients receiving IMR-687 spent 3 months on the lower dose before escalation to the higher dose.
The analysis provides evidence that IMR-687 is safe, tolerable and is able to induce HbF expression in SCD patients. The key takeaways from this analysis are:
19 June 2020 is officially designated World Sickle Cell Day. On 22nd December 2008, the United Nations General Assembly adopted a resolution that recognises sickle cell disease as a public health problem and “one of the world’s foremost genetic diseases.” The international awareness day is observed annually with the goal to increase public knowledge and an understanding of sickle cell disease, and the challenges experienced by patients and their families and caregivers.