Research & Development
Sangamo Releases Preliminary Results from the First Three Patients in a Phase 1/2 Study Evaluating ST-400 Ex Vivo Gene-edited Cell Therapy in Beta Thalassemia
9 December 2019 - - US-based genomic medicine company Sangamo Therapeutics, Inc. (NASDAQ: SGMO) has released preliminary results from the first three patients treated in the Phase 1/2 THALES study evaluating investigational ST-400 ex vivo gene-edited cell therapy in transfusion-dependent beta thalassemia, the company said.

The data are featured in a poster presentation on December 9, 2019 at the 61st annual meeting of the American Society of Hematology in Orlando, FL.

The ST-400 ASH poster will be available on Sangamo's website in the Investors and Media section under Events and Presentations at the beginning of the poster session at 10am eastern time.

Beta thalassemia is a rare blood disorder caused by a mutation in the beta-globin gene that results in impaired production of red blood cells.

ST-400 is an autologous cell therapy candidate that uses gene editing to modify a patient's own hematopoietic stem cells to produce functional progeny red blood cells by increasing fetal hemoglobin.

In the THALES study, hematopoietic stem and progenitor cells (HSPCs) are collected from the patient, modified using zinc finger nuclease gene editing technology to disrupt the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan.

To date, ST-400 has been manufactured for five patients, three of whom had been treated at the time of the ASH data cut. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, and with the support of a grant from the California Institute for Regenerative Medicine.

The three patients treated with ST-400 experienced prompt hematopoietic reconstitution, demonstrating neutrophil engraftment in 14-22 days and platelet engraftment in 22-35 days (Table 1).

No emerging clonal hematopoiesis has to date been observed by on-target indel pattern monitoring in the three treated patients. Reported adverse events are consistent with the known toxicities of mobilization, apheresis, and myeloablative busulfan conditioning.

One serious adverse event related to ST-400 was reported.

As previously disclosed, Patient 1 experienced hypersensitivity during ST-400 infusion considered by the investigator to be likely related to the product cryoprotectant excipient, DMSO, and which resolved by the end of the infusion.

Patient 1, age 36, has a β0/β0 genotype, the most severe form of TDT, and had 27 annualized packed red blood cell events prior to enrollment into the study.

The patient underwent a second cycle of mobilization and apheresis due to the low cell dose and potency achieved in the first cycle.

In both ST-400 lots, editing efficiency was approximately 25%, which was lower than the other patients enrolled in the study and 12 trial-run lots manufactured at clinical scale (71% median editing efficiency).

On-target indels in the infused ST-400 product were 23%, and the CD34+ cell dose was 5.4 x 106 cells/kg. Indels have persisted in peripheral leukocytes through Month 9.

Following ST-400 infusion, fetal hemoglobin levels increased to approximately 2.7 g/dL at Day 56 and remained elevated compared to baseline at 0.9 g/dL at week 39, the most recent measurement at the time of the ASH data cut.

After an initial transfusion-free duration of six weeks, the patient resumed intermittent PRBC transfusions, with an overall 33% reduction in annualized PRBC units transfused since engraftment.

Patient 2, age 30, is homozygous for the severe β+ IVS-I-5 mutation and had 18 annualized PRBC events prior to enrollment into the study.

On-target indels in the ST-400 product were 73%, with a CD34+ cell dose of 3.9 x 106 cells/kg, the lowest seen across the ST-400 lots manufactured for the 5 enrolled patients. Indels have persisted in peripheral leukocytes through Month 6.

Following ST-400 infusion, fetal hemoglobin levels increased as compared with baseline, but have been A) genotype, were dosed after the time of the ASH data cut.

Sangamo expects to enroll a sixth and final patient in the study in the coming months. Results from additional patients and longer-term follow-up data are expected in the second half of 2020. Sanofi is running a parallel clinical trial with BIVV003, which uses a similar approach in sickle cell disease.

The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia.

The age range for the 5 patients enrolled is 18-36 years. ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology.

The THALES study inclusion criteria include all patients with TDT (β0/β0 or non- β0/β0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA recently granted Orphan Drug status to ST-400.

Sangamo Therapeutics is committed to translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, and in vivo genome editing and gene regulation.
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