ACN-8337:  ORAL GRANULOCYTE-COLONY STIMULATING FACTOR FOR NEUTROPENIA

ACN-8337 is an orally available human granulocyte-colony stimulating factor (G-CSF) for the treatment of neutropenia.  Animal data indicates that oral ACN-8337 increases circulating white blood cell counts to levels comparable to subcutaneous injection of Neupogen, while extending the duration of the increased blood cell counts.

ACN-8337, utilizes  transferrin, a natural carrier protein, for the oral administration of recombinant protein products.  Next generations of this product may include oral erythropoietin (e.g. Epogen)  used to stimulated the production of red blood cells for patients with chronic renal failure or cancer, and/or oral formulations of other therapeutic proteins such as growth factors, blood clotting factors, growth hormones, reproductive hormones, or replacement enzymes.

What is G-CSF?

G-CSF (granulocyte-colony stimulating factor) is a hematopoietic (blood forming) growth factor that stimulates the bone marrow to produce more white blood cells. Growth factors are special proteins, which are produced naturally in the body.  In oncology and hematology, a recombinant form of G-CSF is used with certain cancer patients to accelerate recovery from neutropenia (a hematological disorder characterized by an abnormally low number of neutrophil granulocytes, a type of white blood cell) after chemotherapy, allowing higher-intensity treatment regimens. Chemotherapy can cause myelosuppression (a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets) and unacceptably low levels of white blood cells, making patients prone to infections and sepsis. G-CSF is also used to increase the number of hematopoietic stem cells in the blood of the donor before collection by leukapheresis (a laboratory procedure in which white blood cells are separated from a sample of blood) for use in hematopoietic stem cell transplantation. It may also be given to the recipient, to compensate for conditioning regimens.

CURRENT USE OF RECOMBINANT G-CSF

The recombinant human G-CSF synthesized in an E. coli expression system is called filgrastim. The structure of filgrastim differs slightly from the structure of the natural glycoprotein. Most published studies have used filgrastim. Filgrastim (Neupogen) and PEG-filgrastim (Neulasta) are two commercially available, forms of rhG-CSF.

Injectable recombinant protein therapeutics are widely used to stimulate the production of white blood cells in cancer and bone marrow transplant patients, and to stimulate the production of red blood cells in patients with chronic renal failure or cancer patients on chemotherapy. Such therapies are also used to reduce the need for preoperative blood transfusions in patients undergoing elective surgeries. All of these proteins are currently only delivered via subcutaneous injection.

The worldwide market for injectable colony stimulating factors, such as Neupogen and Neulasta is in excess of $3 Billion and in Q1 2008, sales for Neupogen and Neulasta totaled to $223 MIL and $569 MIL respectively.