INDIANAPOLIS--(BUSINESS WIRE)--Semafore Pharmaceuticals announced today that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to the Company’s SF1126 product candidate for the treatment of B-cell chronic lymphocytic leukemia (CLL). In April 2010, the Company initiated an expansion of its ongoing Phase I clinical study into this disease setting. SF1126 is a novel peptidic prodrug that converts to LY294002, one of the most widely studied small molecule inhibitors of both phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR).
“SF1126 is the first PI3K inhibitor to receive orphan drug designation from the FDA for the treatment of CLL, which is an important milestone for Semafore Pharmaceuticals,” said Joseph Garlich, Ph.D., Semafore’s Chief Scientific Officer. “We are committed to developing SF1126 as a potential treatment for this disease and look forward to presenting interim clinical data at ASH.”
SF1126 will be the subject of a poster presentation at the 52nd American Society of Hematology (ASH) Annual Meeting and Exposition being held December 4-7, 2010 in Orlando, FL. A summary of the presentation is below, and the full abstract can be accessed on the ASH website at www.hematology.org.
Phase I Study of Novel Prodrug Dual PI3K/mTOR Inhibitor SF1126 In B-Cell Malignancies
- Saturday, December 4, 2010, 5:30 p.m. to 7:30 p.m. Eastern Time (ET)
- Abstract number: 1783
- Poster Session: Lymphoma - Chemotherapy, excluding Pre-Clinical Models: Poster I
- Location: Hall A3/A4, Poster Board I-763
- Senior author: Daruka Mahadevan, MD, Ph.D., Arizona Cancer Center, University of Arizona, Tucson, AZ
About Orphan Drug Designation
The United States Orphan Drug Act of 1983 was created to promote the development of new drug therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States. Orphan status entitles Semafore Pharmaceuticals to seven years of marketing exclusivity for SF1126 upon regulatory approval, as well as the opportunity to apply for grant funding from the U.S. government to defray costs of clinical trial expenses, tax credits for clinical research expenses and potential exemption from the FDA's application user fee.
About Chronic Lymphocytic Leukemia (CLL)
CLL is a type of cancer that starts from white blood cells (called lymphocytes) in the bone marrow and can spread through the blood to the lymph nodes, spleen, liver and other parts of the body. According to the American Cancer Society, CLL is the most common adult leukemia, accounting for one-third of all leukemia in the United States. Nearly 94,000 Americans are living with CLL and more than 15,000 new cases will be diagnosed this year.
About SF1126 and the PI3K Pathway
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is vital to several essential biological processes, such as cell growth, survival, motility, and metabolism. PI3K is commonly altered in human cancers, making inhibition of the target attractive for cancer therapy. However, the role of PI3K in a wide range of normal biologic processes raises potential concerns about its inhibition in non-cancerous tissues.
As the only PI3K/mTOR inhibitor prodrug currently in development, Semafore’s SF1126 product candidate is designed to overcome these concerns by accumulating preferentially in tumor tissue in an attempt to maximize efficacy and minimize toxicity. SF1126 is a peptidic prodrug that converts to LY294002, one of the most widely studied dual PI3K/mTOR inhibitors that historically suffered from poor solubility. LY294002 is conjugated to an Arg-Gly-Asp (RGD) peptide via a cleavable linker to form SF1126, which has improved properties for clinical use. As a prodrug with improved solubility and site selectivity due to targeting of RGD-recognizing integrin receptors, SF1126 opened up a new avenue for the clinical development of LY294002.
To date, nearly 50 patients with solid tumors or hematological malignancies have been treated with SF1126 in Phase I trials. Administration of SF1126 at doses ranging from 90 to 1,110 mg/m2 has been generally well tolerated with the most common treatment-related adverse events have been nausea, vomiting, diarrhea, fever, and fatigue.
About Semafore Pharmaceuticals
Semafore Pharmaceuticals is a private, clinical-stage biotechnology company dedicated to the discovery and development of novel small molecule signal transduction inhibitors targeting the phosphoinositide-3-kinase (PI3K) pathway for the treatment of cancer and other serious diseases. In addition to SF1126, the Company is developing SF2626, a next-generation dual MEK/PI3K inhibitor that is designed to simultaneously inhibit an additional key pathway critical to cancer progression using a single molecule. For more information see the company’s web site at www.semaforepharma.com.