Biogen Idec and Sangamo BioSciences, Inc. have entered into an exclusive worldwide collaboration and license agreement focused on the development of therapeutics for haemoglobinopathies, inherited conditions that result from the abnormal structure or underproduction of haemoglobin.

The agreement will enable Biogen Idec to further enhance its expertise in non-malignant hematology by leveraging Sangamo’s proprietary genome-editing technology platform to develop treatments targeting sickle cell disease (SCD) and beta-thalassemia.

“Our collaboration with Sangamo is expected to help us expand our capabilities to develop treatments for people with serious, inherited hematologic conditions,” said Douglas E. Williams,  Biogen Idec's executive vice president of research and development. “Building upon emerging science related to fetal haemoglobin regulation, we intend to develop Sangamo’s novel gene-editing technology to create a single approach that has the potential to functionally cure both sickle cell disease and beta-thalassemia.”

Sangamo’s proprietary zinc finger nuclease (ZFN) genome-editing technology enables multiple pathways to treat SCD and beta-thalassemia. The technology can be used to precisely target and knock out key regulators of gene expression, or can be used to precisely insert a new corrective gene to replace the defective copy.

“We are delighted to partner our haemoglobinopathies programs with Biogen Idec,” said Edward Lanphier, Sangamo’s president and chief executive officer. “Biogen Idec is a leader in drug development and has a history of successfully translating cutting edge science into treatments that provide life-changing clinical benefit for patients. This alliance is further validation of our ZFP platform as a transformative technology and accelerates our goal of developing a novel class of therapeutics which has the potential to revolutionize the treatment of genetic diseases.”

Under the terms of the agreement, Sangamo is responsible for all research and development activities through the first clinical proof of concept trial in beta-thalassemia, and both companies will perform activities to enable submission of an Investigational New Drug (IND) application for SCD. Biogen Idec will be responsible for subsequent worldwide clinical development and commercialization of products arising from the alliance. Sangamo retains an option to co-promote any licensed product to treat SCD and beta-thalassemia in the United States.

Biogen Idec will provide Sangamo with an upfront payment of $20 million and will reimburse Sangamo for its internal and external research and development programme-related costs. Sangamo may also receive additional payments of approximately $300 million based on the achievement of certain development, regulatory, commercialization and sales milestones, as well as double digit royalties on product sales.

The transaction has been approved by the boards of directors of both companies and is subject to customary closing conditions including expiration of the applicable waiting period under the Hart–Scott–Rodino Antitrust Improvements Act of 1976 in the United States.
 
Sangamo’s proprietary ZFN genome-editing technology enables multiple approaches to the correction of SCD and beta-thalassemia. Both diseases manifest after birth, when patients switch from producing functional fetal gamma-globin to a mutant form of adult beta-globin, which results in their condition. Naturally occurring increased levels of therapeutic fetal haemoglobin have been shown to reduce the severity of both SCD and beta-thalassemia disorders in adulthood. In haematopoietic stem cells (HSCs), Sangamo’s genome editing can be used to precisely disrupt key transcriptional regulators to reverse the switch from expression of the mutant adult beta-globin back to the production of functional fetal gamma-globin, or the technology can be used to precisely insert a new corrected beta-globin gene to replace the defective copy. Data from this program were recently presented at the 55th Annual Meeting of the American Society of Hematology (ASH).

A bone marrow transplant (BMT), of HSCs from a “matched” related donor (allogeneic BMT) is curative for both diseases. However, this therapy is limited due to the scarcity of matched donors and the significant risk of Graft versus Host Disease (GvHD) after transplantation of the foreign cells. By performing genome editing in HSCs that are isolated from and subsequently returned to the same patient, an autologous HSC transplant, Sangamo's approach eliminates both the need for a matched donor and the risk of acute and chronic GvHD. The ultimate goal of this approach is to develop a one-time curative treatment for SCD and beta-thalassemia.

In May 2013, Sangamo was awarded a $6.4 million Strategic Partnership Award from the California Institute for Regenerative Medicine (CIRM) to develop this potentially curative ZFP Therapeutic for beta-thalassemia. The four-year grant provides matching funds for preclinical work that will support an IND application and a Phase 1 clinical trial in transfusion-dependent beta-thalassemia patients, which will be carried out at Children’s Hospital & Research Center Oakland, and City of Hope.

Mutations in the genes encoding beta-globin, a subunit of the oxygen-carrying protein of red blood cells, lead to the haemoglobinopathies SCD and beta-thalassemia. The mutation in beta-globin that gives rise to SCD causes the red blood cells to form an abnormal sickle or crescent shape making them adherent, fragile and less able to deliver oxygen to tissues, and they can become lodged in small blood vessels and interrupt healthy blood flow. These problems further decrease the amount of oxygen flowing to body tissues. Almost all patients with SCD have painful episodes (called crises), which can last from hours to days, and have progressive organ damage, resulting in shortened lifespan. Current standard of care is to manage and control symptoms, and to limit the number of crises. Current treatments, including blood transfusions, iron-chelation therapy and administration of hydroxyurea, pain medications and antibiotics, do not address the underlying cause of disease, and life expectancy remains substantially reduced in patients with SCD. The CDC estimates that there are currently 90,000 to 100,000 Americans living with SCD which occurs in approximately 1 out of every 500 African-American births and 1 out of every 36,000 Hispanic-American births.

There are several forms of beta-thalassemia caused by mutations in the beta-globin gene; broadly the disorder results in excessive destruction of red blood cells leading to life-threatening anemia, enlarged spleen, liver and heart, and bone abnormalities. Beta-thalassemia major is a severe form of thalassemia that requires regular, often monthly, blood transfusions and subsequent iron-chelation therapy to treat iron overload. The CDC estimates that 2,000 people have beta-thalassemia in the United States, and an unknown number carry the genetic trait and can pass it on to their children. Thalassemia is most common among people of Mediterranean descent and is also found among people from the Arabian Peninsula, Iran, Africa, Southeast Asia and Southern China.

Through cutting-edge science and medicine, Biogen Idec discovers, develops and delivers to patients worldwide innovative therapies for the treatment of neurodegenerative diseases, hemophilia and autoimmune disorders.

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and genome editing.