Sangamo Searching for Options After Sanofi Withdraws from SCD Program


Brisbane, California-based Sangamo Therapeutics announced that Sanofi US was returning its rights to SAR445136 as it shifts its approach from personalized cell therapies to allogeneic off-the-shelf genomic approaches. SAR445136 is a zinc finger nuclease gene-edited cell therapy being developed for sickle cell disease (SCD). The rights return to Sangamo by the middle of this year.

One of the surprising elements here is that the two companies presented data on the therapy at the American Society of Hematology meeting in mid-December. The data was promising, even though only based on four patients. However, the therapy was facing competition from numerous other companies, including CRISPR Therapeutics and Vertex Pharmaceuticals, who presented promising data the year before on CTX001. This therapy is based on CRISPR-Cas9 gene editing, whereas SAR445136 uses zinc finger nucleases to edit stem cells. Both are designed to decrease the expression of BCL11A, a transcription factor that typically suppresses production of fetal hemoglobin.

The data Sangamo and Sanofi presented was on the Phase I/II PRECIZN-1 trial. As of the September 22, 2021 cutoff date, the patients treated most recently had been followed for 26 weeks, with the longest-treated patient followed for 91 weeks. None of the four patients receiving the therapy required blood transfusions after engraftment. Total hemoglobin stabilized by Week 26 in all patients, while fetal hemoglobin level increased from 0.1-11% at screening to 14-39% by Week 26 in all patients, with 38% in the longest-treated patient at 91 weeks.

 “These preliminary proof of concept efficacy and safety results support the potential therapeutic value of the zinc finger nuclease-mediated modification of the BCL11ESE region,” said Karin Knobe, head of development, rare diseases and rare blood disorders at Sanofi, at the time.

Now that Sanofi has backed out, Sangamo is looking for a new collaboration partner or otherwise exploring ways to advance the program. The company indicated Sanofi decided to end the deal after a recent change in its cell therapy strategy.

Dr. John Reed, M.D. Ph.D., global head of research and development at Sanofi, said, “Although the preliminary Phase I/II clinical data for the autologous sickle cell treatment are encouraging, Sanofi has made the decision to terminate the collaboration on the SAR445136 program, which is consistent with our strategy to focus on universal genomic medicine approaches. Sangamo has been a good partner and this decision is not a reflection on the potential of the SAR445136 program. We continue to view them as a pioneer in the area of genomic medicines and will explore other possible collaboration opportunities as we work together to transition the autologous sickle cell program back to Sangamo.”

Sangamo expects the Phase I/II PRECIZN-1 trial of SAR445136 to wrap as planned, and Sanofi will continue to pay for the trial until June 28, 2022, the deal’s final termination date.

SAR445136 is manufactured by ex vivo gene editing of a patient’s own hematopoietic stem cells using non-viral transport of zinc finger nuclease technology that targets the BCL11a gene erythroid-specific enhancer (ESE). The drug received Fast Track Designation from the U.S. Food and Drug Administration and Orphan Medicinal Product Designation from the European Medicines Agency.

Sanofi picked up an allogeneic cell therapy platform in 2021 when it acquired Kiadis Pharma for $359 million. “We believe Kiadis’ ‘off the shelf’ K-NK cell technology platform will have broad application against liquid and solid tumors, and create synergies with Sanofi’s emerging immuno-oncology pipeline, providing opportunities for us to pursue potential best-in-disease approaches,” Reed said at the time. NK cells hunt out and identify malignant cancer cells.

The deal with Sangamo began in 2014. In 2018, Sanofi acquired Bioverativ, a spinout of Biogen, for about $11.6 billion. Bioverative spun out from Biogen’s hemophilia unit in January 2017, and had two drugs, Electate for Hemophilia A and Alprolix for Hemophilia B. In addition to those two marketed products, Bioverativ had a pipeline that included drugs for cold agglutinin disease, hemophilia, sickle cell disease and beta-thalassemia. In 2021, Sanofi licensed two early-stage SCD programs that came out of Bioverativ to Global Blood Therapeutics. The products were reportedly complementary to Oxbryta (voxelotor) tablets, a novel hemoglobin S polymerization inhibitor that was approved by the FDA for SCD in people 12 years and older.

Sandy Macrae, chief executive officer of Sangamo, said, “We remain committed to progressing this program and believe SAR445136 has the potential to relieve people living with sickle cell disease of some of their most challenging symptoms.”

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