Sangamo saw its stock on the up this morning after it posted updates to a series of its trials using a new form of gene editing and cell therapies.
The biotech had a tough start to 2019, posting lackluster data two months back from a phase 1/2 trial of genome-editing therapy SB-913. The treatment failed to have the hoped-for effects on patients with the rare disease MPS II, causing investors to drive Sangamo’s stock down 30%.
But this morning, Sangamo, which focuses on zinc finger nuclease (ZFN) technology (differentiated from and rivaling CRISPR), released a batch of early data. Shares were off around 2% yesterday when it previewed the announcement, but jumped as high as 50% in early trading this morning on the actual update.
Here’s the latest data: First up, a sneak peek at ST-400, an ex vivo gene-edited cell therapy for beta thalassemia, a blood disorder that reduces the production of hemoglobin, which in turn can lead to a lack of oxygen in many parts of the body. The drug is being developed by Sangamo in partnership with Sanofi.
ST-400 works as an autologous cell therapy and involves a process of gene editing a patient's hematopoietic stem cells (HSCs) using non-viral delivery of ZFN.
Sangamo released data from just one patient—the first patient, in fact, treated with ST-400 in the phase 1/2 THALES study, and a patient who has the most severe form of transfusion-dependent beta thalassemia (β0/β0).
For two years prior to treatment in the study, this patient received packed red blood cell transfusions every other week.
Things didn’t start well during the ST-400 infusion; the patient experienced “a serious adverse event,” according to the biotech. Specifically, the patient experienced a transient allergic reaction considered related to the cryoprotectant present in the product.
But the biotech appeared to have this covered, as it says in a statement that: “Thereafter, the post-transplant clinical course was routine.”
The data are clearly early and in a very small patient population, i.e., just one person, but Sangamo says the patient “demonstrated neutrophil and platelet recovery, within two and four weeks of infusion, respectively, indicating that ST-400 successfully reconstituted hematopoiesis following conditioning.”
It also found indels (small insertions or deletions generated at the targeted DNA sequence) in circulating white blood cells, which essentially means Sangamo was successful in editing the BCL11A gene as well as the 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 company said. In short, it looks like it’s working.
Angela Smith, M.D., associate professor in the Division of Pediatric Blood and Marrow Transplantation at the University of Minnesota, said: “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.
“These initial results are especially encouraging given the patient's β0/ β0 genotype, a patient population which has proved to be difficult-to-treat and where there is high unmet medical need.”
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Sangamo is still enrolling in THALES and is planning to release more ST-400 data in the fourth quarter of 2019, including results from additional patients. “Until that time, Sangamo is not planning to report additional clinical data from the program,” the company added.
It also gave a small update on SB-913, the therapy which caused Sangamo a lot of pain back in February. SB-913 uses Sangamo’s ZFN technology to make cuts in the DNA of certain liver cells and insert a functional copy of the IDS gene, which encodes for an enzyme that patients with MPS II lack. If SB-913 raises levels of the enzyme, patients may be able to break down glycosaminoglycans (GAGs) that would otherwise accumulate and cause harm including organ damage.
The interim phase 1/2 CHAMPIONS results posted at the start of the year contained, however, scant evidence that SB-913 can live up to that billing. In five of the six patients enrolled in the study, IDS activity and GAG levels scarcely changed in the 24 weeks following administration of SB-913.
Today, Sangamo said it plans to begin a new trial of the therapy in the second half of the year using second-generation ZFNs and is slated to use data from this study to “make a phase 3 decision for the SB-913 program in 2020.”
It added that 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.”
However, Sangamo will no longer trial 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.”
And that’s not all: There was also an update on its Pfizer-partnered phase 1/2 Alta study for SB-525, a gene therapy for severe hemophilia A.
“The interim data from the first eight patients with hemophilia A treated with SB-525 gene therapy in the Alta study are encouraging and demonstrate a dose-dependent relationship, evidence of sustained factor levels, and low variability, both within each patient and within each cohort,” explained Edward Conner, M.D., chief medical officer at Sangamo.
“These interim results suggest that SB-525 may be well-tolerated and may prove to have the predictability and sustained treatment effect that can bring clinical benefit in patients with hemophilia A. We need to continue observing how the data mature and how additional patients in the expansion cohort respond to SB-525. We look forward to working with Pfizer to potentially advance SB-525 into a registrational study.”
Longer-term follow-up data “will be presented at an upcoming scientific meeting," the companies said, but they will be boosting the study’s fourth cohort with a further five patients, and enrollment is already underway.