Company Overview - Fulcrum Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing small molecules to improve the lives of patients with genetically defined rare diseases, particularly in areas of high unmet medical need [4] - The company's lead clinical program is pociredir, designed to increase fetal hemoglobin expression for the treatment of sickle cell disease (SCD) [4] Clinical Development - Fulcrum will present 12-week results from the 20 mg dose cohort of the Phase 1b PIONEER trial of pociredir in sickle cell disease on February 24, 2026 [1] - Pociredir is an investigational oral small-molecule inhibitor of Embryonic Ectoderm Development (EED), leading to downregulation of fetal globin repressors and increased fetal hemoglobin [5] - In the PIONEER trial, pociredir has shown dose-dependent increases in fetal hemoglobin, improvements in markers of hemolysis and anemia, and has been generally well-tolerated with no serious adverse events reported [5] Expert Involvement - Dr. Martin Steinberg, a prominent hematologist with extensive research on sickle cell disease, will join Fulcrum management for the conference call [2][3] - Dr. Steinberg has published over 450 articles and has contributed significantly to understanding the genetic basis and pathophysiology of sickle cell disease [3] Regulatory Status - Pociredir has received Fast Track and Orphan Drug Designation from the FDA for the treatment of sickle cell disease [5] Disease Background - Sickle cell disease is a genetic disorder caused by a mutation in the HBB gene, leading to inefficient oxygen transport and sickle-shaped red blood cells, which can cause various serious health complications [6]

Core Viewpoint - AB Science has received a formal patent grant in the United States for masitinib in the treatment of sickle cell disease, providing intellectual property protection until November 2040, which strengthens its portfolio for a treatment addressing a significant unmet medical need [1][2]. Group 1: Masitinib and Sickle Cell Disease - Masitinib is being developed to treat the most severe forms of sickle cell disease (SCD), which account for approximately 65% of cases, and poses a major public health challenge [1][2]. - Current treatment options for SCD, such as hydroxyurea and red blood cell transfusions, do not fully address the complications, indicating a high unmet medical need for effective therapies [6][10]. - The disease affects millions globally, with around 300,000 children born with SCD each year, and the number is projected to reach 400,000 by 2050 [4]. Group 2: Clinical Development and Funding - The clinical development of masitinib in SCD is part of the SICKMAST collaborative program, which is fully funded with 9.2 million euros, aiming to demonstrate efficacy in a phase 2 clinical trial [2][3]. - The phase 2 study is designed in two steps, focusing on identifying biomarkers and demonstrating the efficacy of masitinib in treating acute and chronic complications of SCD [3]. Group 3: Mechanism of Action - Masitinib targets mast cells, which play a critical role in severe forms of SCD and its complications, such as vaso-occlusive crises and acute chest syndrome [2][8]. - Preclinical studies have shown that masitinib provides a survival benefit in SCD mouse models, preventing vaso-occlusive crises and acute lung injury [2][8]. Group 4: Current Treatment Landscape - Existing treatments like allogeneic stem cell transplantation and gene therapy are limited to a minority of patients due to toxicity and high costs, highlighting the need for new therapeutic approaches [6][10]. - Anti-P-selectin antibodies and other previously considered treatments have failed to confirm efficacy, further emphasizing the demand for innovative solutions in managing SCD [7][10].