Scribe signs another big pharma deal

Picking out potential winners in the burgeoning gene editing space is tricky, with new contenders seemingly popping up all the time. But if one measure of success is the amount of big pharma interest then Scribe Therapeutics is doing well.

The private group signed a deal with Lilly this week that will see the companies collaborate on in vivo Crispr-based editing for unnamed neurological and neuromuscular diseases. The technology is still very early, but Scribe’s chief executive, Benjamin Oakes, reckons it could have the edge over older techniques.

While more established Crispr players like Crispr Therapeutics and Intellia use the Cas9 enzyme, Scribe employs an engineered version of a different enzyme, CasX. One advantage is its small size; this means that it could be packaged up in AAV viral vectors, which have a limit on the size of the cargo they can carry.

Delivery

Oakes describes delivery as the “number-one challenge” for gene editing companies. "If I can't get into a cell type it doesn't matter if I can edit the genome."

The ability to deliver via AAVs could therefore be important, especially when looking beyond liver-mediated diseases.

Lipid nanoparticles (LNPs) are currently being used for in vivo editing, but they tend to head to the liver, which has so far limited the scope of the technology.

Some companies are working on LNPs designed to move beyond the liver. However, Oakes is sceptical about the prospects for this kind of research, telling Evaluate Vantage: “Anyone who says they’re confident of being able to deliver LNPs anywhere but the liver is either brave or something else. At the same time, it doesn't mean it's not worth trying.”

For Scribe, which was co-founded by the Crispr pioneer and Nobel Prize winner Jennifer Doudna, AAV delivery will therefore be “the first step”, Oakes says. But the group is also looking at LNPs and other nonviral options.

As for virus-like particles, which have gained attention lately, these will be “top of mind [but] they have their own challenges that are actually more similar to the viral technology”.

More specific?

But Scribe is not the only one going small: privately held Mammoth Biosciences, also co-founded by Doudna, is developing miniature Crispr systems and has hooked Vertex and Bayer as partners.

Oakes says Scribe’s platform, known as X editing, has been “honed for greater activity and specificity” versus other Crispr systems.

On specificity, the chief exec says the group has engineered its enzyme to “change [its] ability to recognise an on-target site versus an off-target site”. He adds that Scribe has shown that it can edit a mutant copy of a gene “while leaving the wild-type copy alone”.

Scribe’s work so far is preclinical, and the company will have to demonstrate that it can also do this in humans. Oakes will not say when the Lilly-partnered projects might enter the clinic, or give details on how the group's collaborations with Sanofi and Biogen have progressed.

Scribe could also have a legal advantage over some other Crispr developers. By using CasX, the group hopes to sidestep the wrangling over intellectual property that has enveloped Cas9.

While Scribe’s deals so far have involved X editing, Oakes is keen to stress that the company has “a second wave of technologies” including epigenetic editing. Scribe also plans to develop its own versions of base and prime editing – technologies emerging behind Crispr – using CasX as a backbone in the way that current base and prime editing groups use Cas9.

“We believe we should try to build the right tool for the job,” Oakes concludes. "I think each technology will and should have its niche, and we should try to find its niche versus having one hammer.”

To read Evaluate Vantage's recent report on gene editing and new delivery technologies click here.