For years, clinical-stage biopharmaceutical company Fulcrum Therapeutics (“Fulcrum”) has worked to develop therapies for patients with rare genetic disorders and diseases. Somewhat recently, their focus was on treating beta thalassemia and sickle cell disease (SCD). Their therapy, FTX-6058, is designed to increase fetal hemoglobin levels while also reducing disease progression. Fulcrum announced promising pre-clinical proof-of-concept results at both the Annual Sickle Cell Disease Research and Education Symposium, and the National Sickle Cell Disease Scientific Meeting. Interested in seeing the presentations? You can check them out here.

FTX-6058

Fulcrum developed FTX-6058, an orally administered small molecule which inhibits Embryonic Ectoderm Development (EED), to treat patients with SCD and beta thalassemia. By inhibiting EED, FTX-6058 encourages the expression of Fetal Hemoglobin (HbF). HbF is shown to be protective against SCD and its negative symptoms. Additionally, HbF may prevent disease progression. Currently, Fulcrum believes that FTX-6058 can be administered once daily. However, additional trials are needed to affirm these claims.

Initially, Fulcrum discovered both FTX-6058, and the idea to target EED, through the company’s Product Engine, which uses CRISPR and chemical probe screening. In preclinical studies, the company found that inhibiting EED allowed them to regulate Polycomb Repressive Complex 2 (PRC2), and increase HbF.

Currently, Fulcrum wants to run the first Phase 1 clinical trial to test the safety, efficacy, and tolerability of FTX-6058 by the end of 2020.

Sickle Cell Disease (SCD)

Overall, sickle cell disease (SCD) actually comprises a group of genetic disorders caused by HBB gene mutations. Patients with SCD have poorly formed or malformed red blood cells that are curved like sickles. Because these sickle cells are not flexible, they can get caught along blood vessel walls, blocking blood or causing cell ruptures. SCD affects African Americans much higher than other groups. Symptoms include:

• Extreme pain
• Anemia
• Stroke
• Frequent infections
• Fatigue
• Jaundice (yellowing of the skin and eyes)
• Delayed growth
• Organ damage
• Heart and liver disease
• Loss of kidney function

Learn more about SCD.

Beta Thalassemia

Commonly resulting from HBB gene mutations, beta thalassemia is a blood disorder in which patients have low levels of hemoglobin, a type of protein found in red blood cells. According to the Mayo Clinic, hemoglobin:

is a protein in your red blood cells that carries oxygen to your body’s organs and tissues and transports carbon dioxide from your organs and tissues back to your lungs.

Low hemoglobin not only signifies anemia, but can result in a variety of health issues and symptoms. In terms of beta thalassemia, the condition may be minor, intermediate, or major. Symptoms include:

• Anemia (low red blood cell count)
• Kidney and liver disease
• Pale skin
• Blood clots
• Headaches
• Dizziness and confusion
• Fatigue
• Difficulty breathing
• Frequent bruising or bleeding
• Enlarged spleen

Learn more about beta thalassemia.