This has been a monumental week for gene editing pioneer Intellia Therapeutics (NTLA 0.43%). This was the last of the three original CRISPR companies to start a clinical trial, but it was well worth the wait. Clear signs that Intellia's revolutionary new way to treat inherited diseases actually works have already pushed the stock 93% higher since markets closed last Friday.
The remarkable news pushed shares of Beam Therapeutics (BEAM 2.56%), Editas Medicine (EDIT -0.70%), and CRISPR Therapeutics (CRSP 0.55%), 42%, 35%, and 10% higher, respectively, before the U.S. markets opened this morning.
Intellia's first new drug candidate to begin clinical trials, NTLA-2001, permanently edits a problematic gene inside the body. The first clinical-stage therapy candidate from CRISPR Therapeutics, called CTX001, alters genes in stem cells after they've been removed from the patient. Editas Medicine's first clinical-stage candidate, EDIT-101, is injected into patients' eyeballs and it's supposed to stay there. Beam Therapeutics still hasn't advanced a new drug candidate in clinical-stage testing.
Intellia's lead candidate is a pair of messenger RNA strands surrounded by a specialized fat bubble or lipid nanoparticle (LNP). Unlike Editas Medicine's candidate, NTLA-2001 can safely travel through the bloodstream to reach the liver.
Going into 2020, safely sending RNA strands through the bloodstream so they can instruct cells to produce therapeutic proteins seemed like a far-off dream. Last year, Moderna and BioNTech showed us that LNP technology had finally advanced to a stage that makes RNA-based drugs a real possibility.
The RNA-based vaccines from BioNTech and Moderna instruct human cells to make a spike protein that helps our immune systems immediately recognize the real virus. Intellia's gene therapy for the treatment of transthyretin amyloidosis with polyneuropathy (ATTR-PN) employs RNA, too, but there's a lot more.
The genetic instructions in NTLA-2001 get liver cells to produce a CRISPR-Cas9 complex that specifically disables the transthyretin gene. This prevents transthyretin from entering the bloodstream where it can fall apart and get jammed up in places it doesn't belong.
Intellia's revolutionary gene therapy candidate appears to work even better than hoped. A single dosage of just 0.1 milligrams per kilogram of body weight reduced circulating transthyretin by 52% among three ATTR-PN patients in this group. Among patients given 0.3 milligrams, investigators measured an 87% average reduction.
Alnylam already markets successful therapies for a very limited population of ATTR-PN patients. Intellia's investors are more excited about the successful use of LNP encapsulated mRNA strands to coax cells into producing gene-editing machinery. That's because creating more therapies by swapping transthyretin for different troublesome genes should be relatively simple.
It was nice to see several gene-editing stocks bound higher in response to Intellia's good news, but they probably shouldn't have. That's because Intellia's miles ahead of its peers.
Beam Therapeutics is working on LNP encapsulated RNA strands to treat glycogen storage disorder and alpha-1 antitrypsin deficiency. Beam's unique approach doesn't create double-stranded breaks in DNA the way NTL-2001 does. This should lead to more precise editing and better outcomes down the road. It's going to be a while before we know for certain. The company hasn't even nominated a candidate that uses LNPs and RNA for advancement into human-stage testing yet.
Editas Medicine's lead candidate is in clinical-stage testing. Instead of mRNA encased in an LNP, EDIT-101 uses a viral vector to deliver DNA that instructs cells in the eye to make gene-editing machinery. At the moment it doesn't look like Editas Medicine or CRISPR Therapeutics have any plans to create gene-editing therapies similar to Intellia.