Benzinga | Mar 30, 2021 07:14AM EDT

Forma Therapeutics Announces FT-4202 600 mg Multiple Ascending Dose Cohort Data Supporting Doses Being Evaluated In Phase 2/3 Registrational Trial, Called The Hibiscus Study

Blinded data from the 600 mg dose cohort support the doses (400 mg v 200 mg v placebo) being evaluated in the Hibiscus Study currently enrolling people living with sickle cell disease (SCD)

Doubling the dose of FT-4202 to 600 mg daily for 14 days compared to the previous 300 mg cohort was well-tolerated with no dose-limiting toxicities or treatment-related adverse events observed

Improvements in hematologic (hemoglobin and reticulocytes) and hemolytic (bilirubin and LDH) parameters were comparable to that observed with 300 mg dose, with best response typically at the end of the 14-day treatment period

Across 300 mg and 600 mg cohorts, 10 of 14 (71%) patients on FT-4202 for 14 days achieved a hemoglobin increase ? 1 g/dL from baseline

Forma Therapeutics Holdings, Inc. (NASDAQ:FMTX), a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced new data from its ongoing randomized, placebo-controlled, multi-center Phase 1 trial of FT-4202 in patients with sickle cell disease (SCD) that further support the development of this novel investigational agent, a selective red blood cell (RBC) pyruvate kinase-R (PKR) activator, as a potential disease-modifying therapy. Data previously presented at the 2020 American Society of Hematology (ASH) Annual Meeting were based on the first cohort of patients in the Phase 1 trial dosed with 300 mg of FT-4202 or placebo once daily for 14 days and a 7-day follow up period. The new findings include an analysis of the blinded data from the second cohort of patients randomly assigned to receive 600 mg of FT-4202 or placebo once daily for 14 days and a 7-day follow up period.

"We are excited to see the favorable safety and tolerability profile of FT-4202 at a 600 mg dose, coupled with the overlap of pharmacodynamic activity and biologic effects across the 300 and 600 mg doses, supporting the evaluation of safety and efficacy at an upper range of 400 mg in our Phase 2/3 trial," said Patrick Kelly, M.D., chief medical officer of Forma. "These results after only 14 days of treatment support the potential of FT-4202 to treat the underlying pathophysiology of the disease by increasing hemoglobin and reducing hemolysis, which may reduce the number and severity of vaso-occlusive crises SCD patients may experience annually."

Aggregate findings from the placebo-controlled cohorts of the Phase 1 trial demonstrated 10 of 14 patients (71%) who received FT-4202 achieved a hemoglobin increase of greater than or equal to 1 g/dL from baseline with once-daily dosing of FT-4202 during 14 days of treatment. Based on a trend toward increasing response over the treatment period, the potential exists for additional benefit when dosing beyond 14 days; this is being explored in the ongoing open label extension, which is dosing patients at 400 mg daily for 12 weeks.

The data also showed activation of PKR by FT-4202 increased sickle RBC survival and reduced intravascular hemolysis in patients with SCD based on a reduction in reticulocytes, bilirubin and LDH levels.

Change in hematologic and hemolytic parameters at end of 14-day treatment ascompared to baseline in FT-4202-treated patients (median change)

Dose Cohort Hb ? 1 g/dL Reticulocytes ? LDH ? Bilirubin ?

300 mg 6/7 (1.2 g/dL) 7/7 (-60%) 6/7 (-36%) 7/7 (-35%)

600 mg 4/7 (1.0 g/dL) 7/7 (-45%) 4/7 (-5%) 7/7 (-41%)

Combined 10/14 (1.2 g/dL) 14/14 (-57%) 10/14 (-20%) 14/14 (-37%)

While the data from the 600 mg cohort of patients remain blinded, initial analysis of the cohort suggests FT-4202 has a similar safety and tolerability profile as the 300 mg cohort, despite the doubling of the dose. No dose-limiting toxicities or treatment-related adverse events (AE) were reported, and the overall AE profile of the 600 mg cohort was consistent with the 300 mg cohort.

Unblinded 600 mg cohort data are expected to be reported at an upcoming medical conference in Summer 2021, in addition to initial results from the ongoing open label extension.