Syros seeking new partner for its SCD program after Pfizer ends deal

Syros is developing treatments to promote production of fetal hemoglobin

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by Mary Chapman |

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Pfizer has decided to end a treatment discovery program with Syros Pharmaceuticals that it inherited after acquiring Global Blood Therapeutics (GBT) last year, leaving Syros to seek another partner for the program, which targets two blood disorders, including sickle cell disease (SCD).

The agreement termination was announced in a July 18 Syros filing with the U.S. Securities and Exchange Commission (SEC), the governmental body that regulates and oversees such pacts. The effective date of termination is Oct. 16.

GBT and Syros had partnered in late 2019 to discover, develop, and market new treatments for SCD and beta thalassemia, a blood disorder marked by low levels of hemoglobin, the oxygen-carrying protein in red blood cells.

The agreement called for Syros, using its gene control platform, to find new treatment targets and discover compounds that promoted the production of fetal hemoglobin, a form of hemoglobin found in fetuses.

For its part, GBT had the option to gain an exclusive, global license to develop, produce, and market products derived from those efforts. The company agreed to pay Syros $20 million upfront and fund, up to $40 million, at least three years of investigations.

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Increasing fetal hemoglobin a promising therapeutic approach for adult patients

While fetal hemoglobin swiftly diminishes post-birth, it transports oxygen more efficiently than the protein form normally found in adults. Thus, increasing fetal hemoglobin levels in adults is an enticing therapeutic option for enhancing oxygen transport in those with SCD and beta thalassemia.

This is the underlying mechanism of the sickle cell treatment hydroxyurea, approved in 1998 to help mitigate the frequency of pain crises and the need for blood transfusion in adults.

Syros used its platform to discover gamma globin genes HBG1 and HBG2, which provide instructions for producing fetal hemoglobin and, following birth, are normally switched off.

Two regulators — called LRF and NuRD — could prospectively be used as treatment targets to activate the gamma globin genes and spur fetal hemoglobin production in SCD and beta thalassemia patients.

Around the time of the collaboration, Syros announced the discovery of nuclear factor IX, a new protein that suppresses gamma globin activity, and could potentially be targeted to increase fetal hemoglobin production.

With last year’s $5.4-billion acquisition of GBT, a leader in SCD treatments, Pfizer sought to enhance more than 30 years of therapy development in rare blood diseases.

Pfizer’s SCD treatment portfolio acquired from GBT includes Oxbryta (voxelotor) and two therapies under development, inclacumab and GBT601, both of which received orphan drug and rare pediatric disease designations in the U.S.

With Pfizer stepping away from the agreement, Syros said in the SEC filing it would now “seek to identify a new out-licensing partner for its sickle cell disease program.”

Syros also now loses the $315 million in potential milestone payments that were part of the GBT agreement.