Rare Daily Staff

Global Blood Therapeutics and Syros Pharmaceuticals have entered into a collaboration to discover, develop, and commercialize novel therapies for the inherited blood disorders sickle cell disease and beta thalassemia.

Sickle cell disease (SCD) causes red blood cells to be abnormally shaped in a crescent, or “sickle” shape, which restricts the flow in blood vessels and limits oxygen delivery to the body’s tissues, leading to severe pain and organ damage. It is also characterized by severe and chronic inflammation that worsens vaso-occlusive crises (VOCs) during which patients experience episodes of extreme pain and organ damage.

Beta thalassemia causes reduction in the production of hemoglobin, resulting in a lack of oxygen being delivered in many parts of the body, and anemia. People with beta thalassemia often need lifelong regimens of chronic blood transfusions for survival and treatment for iron overload due to the transfusions.

Under their agreement, Syros will use its gene control platform to identify therapeutic targets and discover drugs that induce fetal hemoglobin, and GBT will receive an option to obtain an exclusive worldwide license to develop, manufacture and commercialize products resulting from the collaboration.

GBT will pay Syros $20 million upfront and fund up to $40 million in preclinical research for at least three years. Should GBT exercise its option under the agreement, Syros could receive up to $315 million in option exercise, development, regulatory, commercialization and sales-based milestones per product candidate and product resulting from the collaboration, plus royalties. Syros also has the option to co-promote the first product resulting from the collaboration in the United States.

“The discovery and development of novel therapeutic approaches to treat sickle cell disease has been a driving force for GBT since we were founded,” said Ted Love, president and CEO of GBT. “We believe that Syros’ approach to inducing fetal hemoglobin is one of the most promising ways to identify the next generation of therapies to treat sickle cell disease and beta thalassemia at a fundamental level – upstream of serious complications such as organ damage, organ failure and early death.”

Using its gene control platform to elucidate mechanisms controlling gamma globin gene expression, Syros identified components of LRF (leukemia/lymphoma-related factor) and the NuRD (nucleosome remodeling and histone deacetylation) complex that could serve as potential targets to switch on the gamma globin gene, which is normally silenced a few months after birth. By turning on gamma globin expression, GBT and Syros aim to induce the production of fetal hemoglobin, which is known to exert protective effects on the red blood cells of patients with SCD and beta thalassemia and mitigate the clinical manifestation of these diseases.

In a recent presentation at the American Society of Hematology meeting, Syros described its discovery of a fetal hemoglobin repressor that, when knocked down in primary cells and an erythroid cell line expressing adult hemoglobin, induced fetal hemoglobin in nearly 100 percent of cells and increased total fetal hemoglobin levels to 40 percent, exceeding levels that are associated with a functional cure in SCD patients.

“We believe it is possible to provide a functional cure for patients with sickle cell disease or beta thalassemia by switching on the gamma globin gene with an oral medicine,” said Nancy Simonian, CEO of Syros. “Partnering with GBT, an established leader in sickle cell disease with proven research, development, manufacturing and commercialization capabilities, allows us to expand and accelerate our program, exploring multiple approaches in parallel with the aim of bringing much-needed new therapies to market for patients with sickle cell disease and beta thalassemia as quickly as possible.”

Photo: Ted Love, president and CEO of GBT

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