Agios Pharmaceuticals, Inc. announced that the global, open-label Phase 3 ACTIVATE-T trial of mitapivat in regularly transfused adults with PK deficiency demonstrated a statistically significant and clinically meaningful reduction in transfusion burden. All 27 patients enrolled in the study were treated with mitapivat. In the 24-week fixed dose period, 37% (n = 10) achieved a =33% reduction in transfusion burden compared to individual historical transfusion burden standardized to 24 weeks (1-sided p=0.0002). In addition, 22% (n = 6) were transfusion-free during the 24-week fixed dose period. Mitapivat is a first-in-class, investigational, oral, small molecule allosteric activator of wild-type and a variety of mutated PKR enzymes. Agios recently reported that its global, randomized, double-blind, placebo-controlled Phase 3 ACTIVATE trial of mitapivat in adults with PK deficiency who do not receive regular transfusions met its primary endpoint, with 40% of patients randomized to mitapivat achieving a hemoglobin response, defined as a =1.5 g/dL sustained increase in hemoglobin concentration from baseline, compared to 0 patients randomized to placebo (2-sided p · 22% of patients dosed with mitapivat (n = 6 of 27) were transfusion-free during the 24-week fixed dose period. Treatment with mitapivat showed a reduction in the annualized total number of red blood cell units transfused during the study compared with the historical transfusion burden. The safety profile observed in the study was consistent with previously reported data. Agios is conducting a full analysis of the ACTIVATE-T results and expects to submit the complete results of the trial for presentation at the European Hematology Association (EHA) Virtual Congress, which is being held June 9-17, 2021. ACTIVATE-T Trial Design: ACTIVATE-T is a global, multicenter, open-label study to evaluate the efficacy and safety of mitapivat in adult patients with PK deficiency who are regularly transfused, defined as receiving six or more transfusions in the past 52 weeks. The trial enrolled 27 patients across North America, Europe and Asia. The study was designed with two parts. Part 1 was a dose escalation period in which patients started at 5 mg twice daily of mitapivat, with two potential dose increases to 20 mg twice daily and 50 mg twice daily for up to 16 weeks. After the dose escalation period, patients received a fixed dose for an additional 24 weeks in Part 2. The primary endpoint of the study was reduction in transfusion burden, defined as a reduction of =33% in the number of red blood cell units transfused during the 24-week fixed dose period compared with the historical transfusion burden standardized to 24 weeks. Participants who discontinued the study before completing at least 12 weeks of treatment in the fixed dose period were considered non-responders. The p-value is based on the binomial exact test of H0: transfusion reduction response rate=10% vs. H1: transfusion reduction response rate>10% at a 1-sided a=0.025.