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United States : Sangamo Provides Clinical Development Update Including Early Phase 1/2 Beta Thalassemia Gene-edited Cell Therapy Data.

Sangamo Therapeutics, Inc. a genomic medicine company, announced recent progress across its clinical portfolio, including early data for ST-400, an ex vivo gene-edited beta thalassemia cell therapy developed in partnership with Sanofi, and next steps for its in vivo genome editing programs. Additionally, in separate announcements, Sangamo today also provided an update on its AAV manufacturing capacity and capabilities, and in a joint press release with partner Pfizer, reported interim data from the SB-525 hemophilia A gene therapy program. These updates will be discussed during a conference call and webcast scheduled for 8:00 a.m. Eastern Time this morning (details below).

"Over the last three years, we've built a solid foundation to support Sangamo's clinical organization and we believe this morning's updates demonstrate how the various components of our clinical development activities are coming together," said Sandy Macrae, Sangamo's Chief Executive Officer. "We are leveraging our technical, clinical, and manufacturing expertise along with our partnerships to create a genomic medicine company with an advancing pipeline of clinical development programs in gene therapy, ex vivo gene-edited cell therapy and in vivo genome editing."

ST-400 ex vivo gene-edited cell therapy for beta thalassemia: ST-400 is an autologous cell therapy that involves gene editing of a patient's own hematopoietic stem cells (HSCs) using non-viral delivery of zinc finger nuclease (ZFN) technology. The first patient treated with ST-400 in the Phase 1/2 THALES study has the most severe form of transfusion-dependent beta thalassemia (?0/?0). For the two years prior to treatment in the study, this patient received packed red blood cell (PRBC) transfusions every other week.

During the ST-400 infusion, the patient experienced a serious adverse event, a transient allergic reaction considered related to the cryoprotectant present in the product. Thereafter, the post-transplant clinical course was routine. The patient demonstrated neutrophil and platelet recovery, within two and four weeks of infusion, respectively, indicating that ST-400 successfully reconstituted hematopoiesis following conditioning.

Indels (small insertions or deletions generated at the targeted DNA sequence) have been detected in circulating white blood cells, indicating successful editing of the BCL11A gene and disruption of the BCL11A erythroid specific enhancer, which is intended to upregulate endogenous fetal hemoglobin production in red blood cells. At seven weeks post ST-400 infusion, total hemoglobin levels remained stable (~9 g/dL), and levels of fetal hemoglobin have continued to rise from approximately 1% of total hemoglobin at the time of infusion to 31% as of the most recent measurement. The patient received several PRBC transfusions for approximately two weeks after the ST-400 infusion. During the subsequent five weeks, the most recent data available, no further PRBC transfusions have been required.

"While these data are very early and will require confirmation in additional patients as well as longer follow-up to draw any clinical conclusion, they are promising. The detection of indels in peripheral blood with increasing fetal hemoglobin at seven weeks is suggestive of successful gene editing in this transfusion-dependent beta thalassemia patient," said Angela Smith, MD, Associate Professor in the Division of Pediatric Blood and Marrow Transplantation at the University of Minnesota. "These initial results are especially encouraging given the patient's ?0/ ?0 genotype, a patient population which has proved to be difficult-to-treat and where there is high unmet medical need." Enrollment in the THALES study is ongoing. Sangamo expects to present longer-term ST-400 data in Q4 2019, including results from additional patients. Until that time, Sangamo is not planning to report additional clinical data from the program. In vivo genome editing programs: Sangamo today also provided an update on its in vivo genome editing programs: SB-913 (mucopolysaccharidosis type II, or MPS II), SB-318 (MPS I), and SB-FIX (hemophilia B).

The Phase 1/2 clinical trials evaluating in vivo genome editing product candidates SB-913 (the CHAMPIONS study for the treatment of MPS II), SB-318 (the EMPOWERS study for MPS I) and SB-FIX (the FIXtendz study for hemophilia B) are ongoing. Data will continue to accumulate throughout 2019, including in the recently treated expansion cohort patients in the CHAMPIONS study, and further updates on these studies are expected later this year. Sangamo expects that no additional patients will be treated at this time with first-generation ZFNs given that clinical benefit has not been demonstrated in analyses conducted to date in ongoing clinical trials and the expected near-term clinical development of second-generation ZFNs.

As previously announced, Sangamo plans to initiate a new clinical trial to evaluate second-generation ZFNs for SB-913 to treat MPS II. In vitro preclinical data presented last year showed three potential advantages of second-generation ZFNs: (1) improvements in efficiency and potency due to structural modifications to the ZFN architecture and expression vector; (2) the ability to function equally well in the patients with a single nucleotide polymorphism (SNP) in the target locus in the albumin gene (~20% of the population); (3) improvements in specificity. The clinical trial of SB-913 using second-generation ZFNs is planned to begin in the second half of 2019. Sangamo expects to use data from this study to make a Phase III decision for the SB-913 program in 2020 and to define the next steps for the SB-318 and SB-FIX programs.

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Publication:Mena Report
Date:Apr 5, 2019
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