GBT and Syros Partner to Develop Sickle Cell Treatments That Boost Fetal Hemoglobin

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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Global Blood Therapeutics (GBT) and Syros Pharmaceuticals have teamed up to discover, develop, and market new therapies for sickle cell disease (SCD) and beta thalassemia.

Under the collaboration agreement, Syros will be responsible for identifying new therapeutic targets and the discovery of drugs that stimulate the production of fetal hemoglobin, using its gene control platform.

GBT will have the option to obtain an exclusive, worldwide license to develop, manufacture and market products resulting from this work.

Fetal hemoglobin, the main form of hemoglobin found in fetuses, rapidly diminishes after birth but is more efficient at transporting oxygen than the form of the protein normally found in adults.

For that reason, increasing the levels of fetal hemoglobin in adults is an attractive therapeutic option for improving oxygen transport in people with SCD and beta thalassemia. (Of note, this is the mechanism of action of hydroxyurea, a medicine that, until 2017, was the only treatment option approved by the U.S. Food and Drug Administration (FDA) to treat sickle cell anemia.

“The discovery and development of novel therapeutic approaches to treat sickle cell disease has been a driving force for GBT since we were founded,” Ted W. Love, MD, president and chief executive officer of GBT, said in a press release.

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“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,” Love said.

Using its platform, Syros discovered two regulators of gamma globin. The gamma globin genes (HBG1 and HBG2) provide instructions for making fetal hemoglobin and are normally switched off shortly after birth.

Two regulators — the leukemia/lymphoma-related factor (LRF) and the nucleosome remodeling and histone deacetylation (NuRD) complex — may potentially serve as therapeutic targets to switch on the gamma globin genes and stimulate the production of fetal hemoglobin in adults with SCD and beta thalassemia.

Syros recently reported the discovery of a new transcription factor called nuclear factor I X (NFIX) that suppresses the activity of the gamma globin and the production of fetal hemoglobin. A transcription factor is a protein that controls the activity of certain genes.

According to data announced by the company in an oral presentation at the recent 61st Annual Meeting of the American Society of Hematology (ASH), blocking NFIX in red blood cell precursors triggered the production of fetal hemoglobin in almost all cells. Fetal hemoglobin levels rose to about 40%, surpassing the levels considered highly effective in treating those with SCD.

“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, MD, chief executive officer 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,” Simonian added.

Under the terms of the agreement, Syros will receive an upfront payment of $20 million from GBT, and will be eligible to receive additional funds up to $40 million for at least three years, which will be used to support preclinical research.

If GBT decides to use its right to obtain an exclusive worldwide license of a product resulting from the partnership, Syros will be eligible to receive up to $315 million for each developmental, regulatory, commercial, and sales milestone achieved by the product.

Syros will also be eligible to receive additional royalty payments based on sales of products resulting from its work with GBT. Syros will also have the option to co-promote the first product in the U.S.