Gene Editing, Results

Sangamo team rushes to defend first human gene editing data as MPS II therapy offers a hit — and a miss

Sangamo $SGMO rolled out its first glimpse at the clinical efficacy of their gene editing therapy for Hunter syndrome (MPS II). And while researchers were able to point to some clear evidence that their approach had an impact on a key biomarker for the disease for 2 patients, there was a critical lack of proof that it was doing specifically what it was designed for.

Understandably, Sangamo concentrated on urinary glycosaminoglycans (GAGs), highlighting big drops for both patients in the second cohort of the tiny exploratory study. 

Ed Conner

The gene editing approach they’ve developed with zinc finger tech is intended to cut into the errant gene and “insert a new copy of the IDS gene into a precise location in the DNA of liver cells to enable a patient’s liver to produce a continuous and stable supply of the missing human IDS enzyme.”

The iduronate-2-sulfatase (IDS) enzyme is needed to break down or recycle glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate. 

The enzyme gene therapy, if it works, would end the need for regular enzyme replacement infusions. And the two patients in cohort two demonstrated mean reductions in GAG, dermatan sulfate and heparan sulfate of 51%, 32%, and 61%.

That’s good.

However, there was also this:

At baseline and for the first 16 weeks post-dosing of SB-913, plasma IDS activity (measurements obtained at trough of weekly ERT dosing) was below the level of quantification of the current assay.

That’s what Twitter began buzzing about, triggering a rapid drop in Sangamo’s shares.  

Sandy Macrae

In a call with analysts, Sangamo execs rushed to fight back against the backlash.

That lack of evidence that the therapy creates the enzyme needed, “doesn’t mean IDS isn’t being produced,” said Sangamo CMO Ed Conner. “Cells of patients with MSP II are starving for IDS.” And “low levels may be sufficient to suppress GAG.”

Sangamo CEO Sandy Macrae also fiercely defended the results, saying you can’t get that hit on efficacy unless the gene editing was taking effect.

In addition, they added that the third cohort in the study is getting a much stronger dose that could have a bigger effect. And execs added that they need to develop a better assay for their clinical work to detect IDS. 

That wasn’t enough to overcome the first reaction by investors. Their stock was down 22% in mid-morning trading.

This trial is crucial for Sangamo, which is looking for clear evidence that it can beat its rivals in the fast-growing field of gene editing. That rivalry, which includes a variety of approaches to editing genes, is just getting started.


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Scientist, Quality Control
Molecular Templates Austin, TX
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Molecular Templates Austin, TX
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Flagship Pioneering Cambridge, MA

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