Therapeutics for Sickle Cell Disease and β-Thalassemia

Normal vs Sickle Cell

Normal red blood cells are round and flexible and can pass through small blood vessels (left). Sickle cells become rigid and deformed, sticky, die rapidly, and obstruct blood flow (right).

Inherited blood diseases which affect hemoglobin A, the protein in red blood cells necessary for oxygen delivery, are called β-thalassemias or sickle cell syndromes. These diseases afflict millions worldwide, and are WHO-designated as a growing global health burden. Fetal hemoglobin (HbF) is another type of hemoglobin which is normally present in all humans, but is suppressed in infancy to levels below 2%.  Decades of research have shown that any incremental increase in HbF reduces the severity of sickle cell disease, or the life-threatening anemia of β-thalassemia. Pharmacologic augmentation of fetal hemoglobin (γ-globin chain) production, to replace defective or missing β-globin chains, is Phoenicia's therapeutic approach.

Blood CellsPhoenicia's HbF Inducer Program focuses on clinically-tested therapies suitable for rapid application in patients with these serious genetic anemias. Beginning with a high-throughput screening program of chemical libraries, and including drugs already FDA-approved for other conditions, Phoenicia scientists identified potent, HbF-inducing drugs with complementary mechanisms of action.

Our lead drug (PB-04), identified for repurposing as a therapeutic for the hemoglobinopathies, is very active in highly-predictive animal models, and has a decades-long record of clinical safety. The drug candidate was recently selected as a project within the Therapeutics for Rare and Neglected Diseases program at the NIH’s National Center for Advancing Translational Sciences. Through our collaboration with TRND researchers, we gain access to preclinical drug development expertise. The goal of the TRND program is to work with collaborators to advance potential treatments to human clinical trials.

In parallel, Phoenicia is determining which patient subtypes are most likely to benefit from specific HbF stimulants, to enhance success in clinical trials. With two NIH-STTR grants, "Next Generation Therapeutics for Hemoglobinopathies" and "In vivo Studies of Clinical Stage Therapeutics," and an NIH R01 grant, "Novel Globin Gene Modulators," investigation of 5 clinic-ready pharmaceuticals is underway in specific disease genotypes or subsets in patients around the world. This investigation will allow our clinical trials to be tailored to those patients most likely to respond well to specific drugs.

Supported by the National Heart, Lung and Blood Institute, and the National Institute of Diabetes, Digestive and Kidney Disorders