recent approaches to treating both disorders are emerging, such as gene therapy and gene editing, with promising early clinical data being observed in each. These approaches, however, are complex, costly, difficult to administer and potentially only suitable for a limited subset of patients.
Based on promising preclinical data and data from a Phase 1 clinical trial of IMR-687 in healthy volunteers, in 2018 we initiated our Phase 2a randomized, double-blinded, placebo-controlled clinical trial of IMR-687 in adult patients with SCD. The goals of this trial were to evaluate the safety, tolerability, pharmacokinetics, or PK, exploratory pharmacodynamics, or PD, and clinical outcomes of IMR-687 administered once daily for 16 or 24 weeks in two populations of patients with SCD: one on monotherapy IMR-687 and one on background hydroxyurea, or HU, in combination with IMR-687 to test drug-drug interaction.
In January 2021, we reported topline results from the Phase 2a clinical trial from the individual sub-studies in the trial. At the 2021 European Hematology Association, or EHA, Annual Congress in June 2021, we reported final data from all 93 patients in the trial, including pooled analyses from the different sub-studies that compared patients who received IMR-687 as part of the trial with those who received placebo. Details of this data are described below under “Recent Developments.”
In March 2021, we reported preliminary data from patients with evaluable data for at least four months of treatment on the OLE clinical trial. At the 2021 EHA Annual Congress in June 2021, we reported additional preliminary data from patients with evaluable data for at least eight months of treatment on the OLE clinical trial. Details of this data are described below under “Recent Developments.”
In the second quarter of 2020, we initiated the Ardent Phase 2b clinical trial of IMR-687 in adult patients with SCD and the Forte Phase 2b clinical trial of IMR-687 in adult patients with ß-thalassemia. We are currently enrolling patients in each trial at the IMR-687 higher dose (once daily dose of 300 mg or 400 mg based on patient weight), IMR-687 lower dose (once daily dose of 200 mg or 300 mg based on patient weight) or placebo. We expect to report interim data from each of these trials in the second half of 2021. Based on the supportive safety and PK data from the Phase 2a interim analyses, we designed the Phase 2b clinical trials to evaluate higher doses, longer treatment periods, and additional clinical endpoints as compared to the Phase 2a clinical trial.
In addition to our clinical programs with IMR-687 in patients with SCD and ß-thalassemia, in the second quarter of 2020, we commenced preclinical development of IMR-687 in heart failure with preserved ejection fraction, or HFpEF. Published literature suggests that the inhibition of PDE9, and resulting increases in cyclic GMP through natriuretic peptide modulation, can serve as an attractive target for the prevention and treatment of vascular disease, including HFpEF. An exploratory analysis co-led by Vanderbilt University Medical Center, or VUMC, on data from the second interim analysis from our Phase 2a clinical trial of IMR-687 demonstrated the potential of IMR-687 to reduce N-terminal pro-B-type natriuretic peptide, or NT-proBNP, a well-established biomarker of cardiovascular risk in patients with SCD. This data was presented at the 15th Annual Sickle Cell and Thalassemia, or ASCAT, Conference in October 2020. In April 2020, we entered into an agreement with the Necker Institute of Paris, France to conduct preclinical studies with IMR-687 in HFpEF. The preclinical data from three established mouse models for HFpEF suggest potential benefits of IMR-687 across several relevant cardiac biomarkers. We are collaborating with VUMC and have engaged additional key opinion leaders in heart failure, with the aim of formulating a clinical development plan for IMR-687 in this indication.
RECENT DEVELOPMENTS
Phase 2a Clinical Trial Data
In January 2021, we disclosed topline results of the Phase 2a clinical trial from the individual sub-studies in the trial, and at the 2021 EHA Annual Congress in June 2021, we reported final data from all 93 patients in the trial, including pooled analyses from the different sub-studies that compared patients who received IMR-687 as part of the trial with those who received placebo.