Overview: CRISPR Technology Headed to Clinical Trials

CRISPR Gene editing

Although much of the recent attention to CRISPR gene editing has been negative, with a focus on Chinese researcher He Jiankui’s use of the technique to modify the genomes of a set of twins and his subsequent arrest and prison sentence, CRISPR still remains one of the great hopes for treating diseases. Some of the focus appears to be shifting toward a more positive story, Boston-based Editas Medicine’s clinical trial of a CRISPR technology in patients with a rare inherited eye disorder, as well as other companies' efforts.

Editas is developing EDIT-101 in partnership with Allergan to treat Leber congenital amaurosis type 10 (LCA10). There are currently no approved therapies for the disease.

Under their partnership, Allergan reserves the right to in-license up to five genome editing programs for eye diseases, including EDIT-101. Editas is entitled to possible milestone payments and royalties for each program.

Charlie Albright, chief scientific officer at Editas, told the Boston Business Journal that editing the genome was the only way to achieve a “potentially transformational and durable change” for patients with the disease. “It’s a super exciting time to be part of the first in vivo experimental medicines going into the clinic.”

Some of the concerns raised by He Jiankui’s research—that there may be unintended off-target gene edits still remain. However, unlike with He Jiankui’s research, the edits are not to the patient’s germlines. This means that any changes to the genomes in patients with LCA10 won’t be transferred to their children. Also, another reason early successes in gene editing are in optical diseases is the ability to inject the genes and the CRISPR packages directly into the intended organ, in this case, the eyes.

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For example, Intellia Therapeutics, another company working on CRISPR-based therapies, is focusing on targeting transthyretin amyloidosis (ATTR). This is a liver disease, and the approach requires a systemic dosing, meaning the virus carrying CRISPR is spread around the body before finding its target.

John Leonard, chief executive officer of Intellia, however, argues the risk is worth it. “The idea of curative therapy is the ultimate objective. You can potentially treat a whole series of tumors that are untreatable at this point.”

Still, investors are showing a significant interest in the companies leading the way, with CRISPR Therapeutics shares up 113% last year, Editas up 30% and Intellia up 7%.

CRISPR Therapeutics, however, plans to make edits outside the body and in well-understood diseases like beta-thalassemia and sickle cell disease. “If it’s ex vivo, we will know exactly what changes we’re making,” said Sam Kulkarni, CRISPR’s chief executive officer. “Then as we build the company, our expertise, and our market cap, and can afford to spend more on this, we can do more and more and we can improve the platform to make smaller Cas9, brand new delivery technologies.”

Cas9 is the enzyme used most commonly in CRISPR to clip out the target DNA sequence.

Kulkarni argues that 60% of the opportunity in the field is in editing genes outside the body. Working with Vertex Pharmaceuticals, CRISPR Therapeutics plans to launch a clinical trial every six months. Three of them will be in cancer, attempting to edit immune cells to attack solid tumors. It also has plans to create an artificial pancreas for diabetic patients.

Silvan Türkcan, an analyst with Oppenheimer, notes that the share prices seen in CRISPR companies are largely related to their partnerships. Previously, these have been difficult for investors to model, but now the companies are starting to behave more like traditional biotech stocks, which is to say, moving up or down based on data readouts.

“We need to see the promise of CRISPR—that you can develop a superior product to gene therapy, precisely—holds up,” Türkcan said.

Editas has also launched investigational new drug (IND) enabling activities for EDIT-301, a CRISPR therapeutic to treat sickle cell disease and beta-thalassemia. Editas has collaborations and deal with Juno Therapeutics, a Celgene company that is now part of Bristol-Myers Squibb. Those deals tend to focus on using CRISPR to engineer T-cells to treat cancer. Editas also has a research and cross-licensing deal with BlueRock Therapeutics, and with AskBio.

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