Rare Daily Staff

Fulcrum Therapeutics, a company focused genetically defined rare diseases in areas of high unmet medical need, raised $125 million in a public offering of common stock.


The recently announced positive interim results of an early-stage dosing study of sickle cell therapy FTX-6058 in healthy adult volunteers helped generate interest in the offering.

The company sold 6.6 million shares at $19 a share. In addition, Fulcrum has granted the underwriters a 30-day option to purchase up to 990,000 additional shares of its common stock at the public offering price, less the underwriting discount and commissions.

Fulcrum’s proprietary product engine, FulcrumSeek, identifies drug targets that can modulate gene expression to treat the known root cause of gene mis-expression.

FTX-6058 is an experimental, potent, and selective small molecule inhibitor of EED designed to increase the expression of fetal hemoglobin (HbF) with the potential to treat hemoglobinopathies, such as sickle cell disease and beta-thalassemia.

Results from the multiple ascending dose portion of the trial demonstrated proof of biology as evidenced by a dose proportional induction in HBG mRNA and accompanying increases in HbF-containing reticulocytes (F-reticulocytes). At 10mg, the highest dose studied to date, the mean changes were 4.5-fold and 4.2-fold, respectively. The increases in F-reticulocytes indicate that the HBG mRNA increases observed with FTX-6058 treatment are translating to HbF protein production.

Sickle cell disease (SCD) is a genetic disorder of the red blood cells caused by a mutation in the HBB gene. This gene encodes a protein that is a key component of hemoglobin, a protein complex whose function is to transport oxygen in the body.

The result of the mutation is less efficient oxygen transport and the formation of red blood cells that have a sickle shape. These sickle shaped cells are much less flexible than healthy cells and can block blood vessels or rupture cells. SCD patients typically suffer from serious clinical consequences, which may include anemia, pain, infections, stroke, heart disease, pulmonary hypertension, kidney failure, liver disease and reduced life expectancy.

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