Dive Brief:

  • Intellia Therapeutics can begin a clinical trial of an experimental gene editing treatment it's developing for a rare, inherited disease, the U.K. drugs regulator declared, clearing the Cambridge, Massachusetts-based biotech to treat the first patient with its therapy later this year.
  • The small, Phase 1 study is set to be the first to test a CRISPR-based gene editing treatment that's infused directly into the blood to change the DNA of cells in the body. Other trials begun recently are studying use of CRISPR gene editing on stem cells extracted from the bone marrow and then reinfused, as well as on cells in the eye via a retinal injection.
  • Intellia aims for its treatment, dubbed NTLA-2001, to be curative by permanently "knocking out" a mutated gene that results in build-up of a misfolded protein called transthyretin. People with so-called transthyretin amyloidosis often have progressive nerve and heart damage that can lead to death.

Dive Insight:

Intellia is one of three high-profile biotechs formed in the first couple years after the discovery of CRISPR/cas9 gene editing by several scientists, among them Jennifer Doudna and Emmanuelle Charpentier, this year's winners of the Nobel Prize in Chemistry.

The other two, CRISPR Therapeutics and Editas Medicine, have already started human studies testing different applications of the revolutionary technology to treat, respectively, the blood diseases beta-thalassemia and sickle cell, and a rare form of genetic blindness.

While all three are far from having a proven medicine, the optimism and enthusiasm for CRISPR's therapeutic potential has buoyed their market value to a combined $11 billion. Gene editing advances, utilizing CRISPR as well as newer techniques, have sprouted several other biotech startups that are just now setting out to follow CRISPR Therapeutics, Editas and Intellia.

Each of three companies is using CRISPR to edit genes either ex vivo, outside the body, or in vivo, inside the body. In the former case, cells are extracted from a patient and then genetically modified in ways that, when reinfused, either bypass or correct disease.

In vivo treatment is a potentially riskier route, involving the alteration of genes directly inside the body, but could allow for more diseases to be treated using CRISPR technology. For the eye disease that Editas hopes to treat with its first therapy, CRISPR gene editing tools can be injected directly into the cells they're designed to fix.

For transthyretin amyloidosis, however, Intellia needs to infuse its treatment systemically to reach the liver cells that churn out the disease-causing protein. By knocking out the mutated transthyretin gene, the company aims to permanently reduce transthyretin protein levels.

The first part of Intellia's study will test a range of treatment doses in 38 patients, before expanding to treat others in a second phase once an optimal dose is chosen. The first patient will be dosed before the end of the year, depending on potential disruption to trial activities from the COVID-19 pandemic.

The company said it is also applying to start testing the therapy in other countries outside of the U.K.

Several treatments for transthyretin amyloidosis have recently become available in the U.S., with Alnylam Pharmaceuticals Onpattro, Ionis Pharmaceuticals' Tegsedi and Pfizer's Vyndaqel winning Food and Drug Administration approvals over the past two years.

For Intellia, the trial clearance is an important step and continues this year's momentum. Shares have risen in value by nearly two thirds since the beginning of January, and the biotech successfully negotiated an expanded a gene editing collaboration with Regeneron in June.

CRISPR gene-editing companies are also back in the spotlight following the award of the Nobel Prize to Doudna and Charpentier this month.

Intellia is connected to Doudna and Charpentier through a sub-license from Caribou Biosciences to patents on the CRISPR technology it uses. Caribou, in turn, licenses CRISPR-related inventions from the University of California, Doudna and Charpentier.

Editas Medicine, by contrast, licenses its CRISPR-related patents from The Broad Institute of MIT and Harvard. The institute and the University of California are locked in a years-long legal fight over which camp's patents should hold primacy in law.



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