Benzinga | Dec 7, 2020 04:35PM EST

Forma Therapeutics Reports Presentation Of Clinical Proof-of-Concept Data at the 62nd Annual ASH Meeting Supporting the Potential of its Novel Investigational PKR Activator, FT-4202, to Treat Sickle Cell Disease (SCD)

)-- Forma Therapeutics Holdings, Inc. (NASDAQ:FMTX), a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced that clinical proof-of-concept in patients with sickle cell disease (SCD) has been observed in the ongoing randomized, placebo-controlled, multi-center Phase 1 trial of FT-4202. FT-4202 is a novel, investigational, selective red blood cell (RBC) pyruvate kinase-R (PKR) activator in development as a potential disease-modifying therapy for SCD. In a cohort of nine patients, six of seven patients (86%) who received FT-4202 achieved a hemoglobin increase of greater than 1 g/dL from baseline with once-daily dosing at 300 mg for 14 days. The data, being presented today at the 62nd American Society of Hematology (ASH) Annual Meeting, also demonstrate improvements in hemolytic parameters showing that activation of PKR by FT-4202 decreases reticulocyte counts and sickle RBC hemolysis in patients with SCD.

"These results are remarkable for a Phase 1 study, and they're encouraging for sickle cell patients," said Marilyn J. Telen, M.D., director of the Duke Comprehensive Sickle Cell Center, Professor of Medicine, Duke University School of Medicine, and one of the study investigators. "The absence of serious treatment-related adverse events, together with increased hemoglobin and reduced markers of hemolysis among the group receiving FT-4202, indicate a potential impact on overall red blood cell health and support further studies."

"We are pleased to present our clinical proof-of-concept data and continue to see potential for FT-4202 to improve the lives of people living with sickle cell disease," said Patrick Kelly, M.D., chief medical officer of Forma. "As we prepare to initiate Forma's pivotal Phase 2/3 trial, we plan to evaluate whether the combined ability of FT-4202 to increase hemoglobin levels in red blood cells and bring about improved red blood cell health will meaningfully reduce the frequent painful vaso-occlusive crises these patients endure."

Presentation Overview

FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Demonstrates Proof of Mechanism and Proof of Concept after a Single Dose and after Multiple Daily Doses in a Phase 1 Study of Patients with Sickle Cell Disease

The data will be presented in an oral presentation by R. Clark Brown, M.D., Ph.D., Pediatric Hematologist/Oncologist, Medical Director of Sickle Cell at Scottish Rite, Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, and Associate Professor of Pediatrics, Emory University School of Medicine.

The results announced today are based on nine patients with SCD (FT-4202 n=7; placebo n=2) randomly assigned to receive a single oral dose of 300 mg daily of FT-4202 or placebo for 14 days. The data show that, from baseline, in patients receiving FT-4202:

* 6 of 7 achieved a > 1 g/dL increase in hemoglobin (Hb); median 1.2 g/dL increase (range 0, 2.3 g/dL);

* 2,3-DPG levels were reduced, thus increasing oxygen affinity and decreasing sickle hemoglobin polymerization;

* Adenosine triphosphate (ATP) levels were increased resulting in improved RBC function and reduced hemolysis;

* 7 of 7 achieved a reduction in reticulocytes; median 60% decrease (range -39%, -81%);

* 6 of 7 achieved a reduction in lactate dehydrogenase (LDH); median 36% decrease (range +18%, -57%); and

* 7 of 7 achieved a reduction in bilirubin; median 35% decrease (range -7%, -63%).

The tolerability data presented today are based on nine patients enrolled at the time of submission of the presentation to ASH. Since then, findings from these nine patients have been unblinded. Among the seven patients receiving FT-4202, the tolerability analysis indicates:

* Eighteen adverse events (AEs) were reported;

* Two Grade 1 AEs considered possibly related to study treatment were reported by one patient each and included headache and nausea;

* No treatment-related serious AEs were reported.

Non-treatment-related AEs were consistent with sickle cell disease-related events commonly experienced in this patient population.

The ongoing Phase 1 study is evaluating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a single ascending dose and multiple ascending doses of FT-4202, first in healthy volunteers and now in patients with sickle cell disease. Based on the safety results and tolerability profile observed in the initial multiple dose cohort of patients, a second multiple dose cohort is being enrolled in which patients are randomly assigned to receive a single daily 600 mg oral dose of FT-4202 or placebo for 14 days. Patients who complete this second 14-day dose cohort can then enroll into a 12-week, open label cohort receiving a single daily 400 mg oral dose of FT-4202. For more information, please visit clinicaltrials.gov/NCT03815695.

The data presented today, along with the results from the single 700 mg dose arm of the study presented in June 2020 at the European Hematology Association (EHA) Annual Congress, support initiation of a randomized, placebo-controlled, double-blind, global multicenter Phase 2/3 registrational study to evaluate the safety and efficacy of FT-4202 in adults and adolescents with SCD in the first quarter of 2021.