Forma Therapeutics Holdings Inc. announced new data from its ongoing Phase 1 trial of etavopivat (formerly referred to as FT-4202) being presented at the 26th Annual European Hematology Association (EHA) 2021 Virtual Congress. The e-poster presentation includes initial data from the open-label extension (OLE) cohort showing etavopivat improved and sustained hematologic and hemolytic parameters for patients living with sickle cell disease (SCD) receiving 400 mg etavopivat once-daily for at least two weeks and up to 12 weeks. Also being presented are the unblinded results from the two multiple ascending dose (MAD) cohorts, which demonstrate once-daily dosing of 300 mg or 600 mg etavopivat for 14 days improved measures of sickle red blood cell (RBC) functional health, with effects persisting in some patients even after treatment discontinuation. Clinical Data Results: In the combined MAD1 (300 mg QD) and MAD2 (600 mg QD) cohorts, 73% (11 of 15) of patients achieved a hemoglobin increase of greater than 1g/dL over baseline; significant improvement in hematologic and hemolytic markers also included decreased absolute reticulocytes (100%, or 15 of 15), decreased LDH levels (73%, or 11 of 15) and decreased indirect bilirubin levels (93%, or 14 of 15). The osmoscan and oxygenscan results from 14 patients showed a statistically significant improvement. Initial results as of May 24, 2021 in the OLE cohort for eight patients receiving etavopivat treatment (400 mg QD) for at least two weeks indicated a hemoglobin increase of greater than 1 g/dL in 88% (7 of 8), with a mean hemoglobin increase of 1.5 g/dL. Patient data indicated a durable response for those patients receiving treatment beyond two weeks, for up to 12 weeks, with improved hematologic and hemolytic parameters. The improvement in RBC functional health extended beyond the 12-week treatment period; in one patient, improved sickle RBC deformability remained for up to four weeks after treatment discontinuation. These initial OLE data support the combined MAD cohort results and show that daily etavopivat treatment also significantly improved hematologic and hemolytic parameters. The safety profile in the OLE cohort was consistent with underlying disease. Of note, two patients reported serious adverse events, including one vaso-occlusive crisis and acute chest syndrome, which was not considered related to treatment by the trial investigator. A deep-vein thrombosis (DVT) report was described as possibly related. Additional results being presented at the conference are measures of RBC functional health, with RBC elongation and point-of-sickling data analysis showing improvements in cell deformability, including durable changes for up to four weeks following treatment. The data show benefits beyond activation of the glycolytic pathway, including enhanced activity of enzymes involved in preventing and repairing oxidative damage and reduced levels of phosphatidyl serine (PS), a marker of membrane damage observed on the surface of sickle RBCs. Early data from the 12-week OLE cohort show favorable systemic biomarkers including lower levels of erythropoietin (EPO), reduced evidence of activation of coagulation (Prothrombin 1.2 and D-dimers) and decreased activation of innate immunity (TNF-a). These biomarkers suggest the potential for a broader benefit to people living with SCD, including the potential to reduce vaso-occlusive crises. Ongoing Trials: The blinded, randomized, placebo-controlled portion of the ongoing Phase 1 trial is complete. People with SCD are now directly enrolling into the ongoing 12-week OLE cohort receiving 400 mg etavopivat daily. Forma is currently enrolling adults and adolescents with SCD into the Hibiscus Study, a registrational Phase 2/3 randomized, placebo-controlled, double-blind, multicenter trial to further evaluate the safety and efficacy of etavopivat in this patient population.