Imara Inc. reported results from its Phase 2a clinical trial of IMR-687 in adult patients with sickle cell disease (SCD). The Phase 2a clinical trial included a total of 93 treated patients across four different sub-studies and was designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical outcomes of escalating doses of IMR-687 administered once daily for 16 to 24 weeks, either as a monotherapy or in combination with hydroxyurea (HU). Overall, the data from the Phase 2a clinical trial demonstrated that IMR-687 was well tolerated as a monotherapy and in combination with HU at all dose levels. There were no observed clinically significant shifts in vital signs or electrocardiogram data, including no hypotension or neutropenia in either the monotherapy or combination arms. Interim data on patients from Populations A and B were previously disclosed, with results from the A1 and B1 populations being reported for the first time. Monotherapy Sub-studies (A/A1): Population A (n=40): Patients received either placebo or IMR-687 at once-daily doses of 50 mg or 100 mg through 12 weeks and then higher doses of 100 mg or 200 mg, respectively, through an additional 12 weeks (24 weeks total). Population A1 (n=18): Patients received either placebo or IMR-687 at a once-daily dose of 100 mg through 4 weeks and then 200 mg through an additional 20 weeks (24 weeks total). Combination Sub-studies (B/B1): Population B (n=21): Patients received either placebo or IMR-687 once-daily at 50 mg on top of a stable dose of standard of care HU, with escalation after 4 weeks to 100 mg for an additional 12 weeks (16 weeks total). Population B1 (n=14): Patients received either placebo or IMR-687 once-daily at 50 mg on top of a stable dose of standard of care HU, with escalation after 4 weeks to 100 mg for an additional 20 weeks (24 weeks total). Population A1 (monotherapy): The most frequent adverse events in the IMR-687 treatment arm included sickle cell anemia with crisis, nausea, headache and back pain and were generally consistent with those observed at two previously reported interim analyses. A 25% lower rate of vaso-occlusive crises/sickle cell-related pain crises (VOCs/SCPCs), as part of the safety analysis, was observed in the IMR-687 treatment group when compared to placebo. 58% of patients (7 of 12, 9 events total) experienced at least one VOC/SCPC in the IMR-687 treatment group as compared to 83% (5 of 6, 14 events total) in the placebo population. Furthermore, the rate of VOC-related hospitalizations was lower in the IMR-687 treatment group when compared to placebo. 33% of patients (4 of 12) experienced one VOC-related hospitalization in the IMR-687 treatment group as compared to 66% (4 of 6) in the placebo population. Biomarker results showed no meaningful changes in F-cells, fetal hemoglobin (HbF) levels, or Hb levels from baseline through week 24. However, a dose-dependent increase in HbF (1.3% absolute increase) was seen when patients dose escalated from 100 mg to 200 mg, starting after 4 weeks and through 24 weeks. One of seven evaluable patients (14%) in Population A1 recorded an absolute increase in HbF percentage from baseline of greater than 1% (increase of 3.2%). Markers of hemolysis that include percent reticulocytes, absolute reticulocyte count, indirect bilirubin and LDH all improved from baseline in a dose dependent manner, with the greatest improvement occurring when patients were on the 200 mg dose. This trend similarly occurred with high sensitivity C-reactive protein (hsCRP) and amino-terminal pro-brain type natriuretic peptide (NT-proBNP) values.